Council for Tobacco Research
Report of the Council for Tobacco Research-U.S.A., Inc. [St]
Abstract
MAR
Fields
- Depository Date
- 25 Sep 1995
- Master ID
- Ctrmn00000667-6967
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- CTRMN000828-0848 by-Laws of the Council for Tobacco Research - U.S.A., Inc. [Rules and Regulations for the Operation of the Council]
- CTRMN000849-0854 Application for Research Grant [A Blank Funding Request Form for Scientific Studies]
- CTRMN000855-0856 Statement of Policy Containing Conditions and Terms Under Which Project Grants Are Made [Stipulations for Receiving A Funding Award]
- CTRMN000857-0859 [Suggestions and Guidelines for Submitting A Request for A Grant]
- CTRMN000860-0871 [Transmittal of Information for Securing A Research Grant]
- CTRMN000872-0882 [A Blank Funding Request Form for Scientific Studies]
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- CTRMN001032-1045 1956 Report of the Scientific Director [St]
- CTRMN001046-1094 1957 Report of the Scientific Director [St]
- CTRMN001095-1127 1958 Report of the Scientific Director [St]
- CTRMN001128-1163 1959 Report of the Scientific Director [St]
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- CTRMN001270-1306 Annual Report of the Scientific Director [St]
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- CTRMN001430-1485 Annual Report of the Scientific Director [St]
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- CTRMN001530-1578 Annual Report of the Council for Tobacco Research-U.S.A., Inc. [St]
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- CTRMN001633-1681 Report of the Council for Tobacco Research-U.S.A., Inc. [St]
- CTRMN001682-1727 Report of the Council for Tobacco Research-U.S.A., Inc. [St]
- CTRMN001728-1771 1975 Report of the Council for Tobacco Research-U.S.A., Inc. [St]
- CTRMN001772-1816 Report of the Council for Tobacco Research-U.S.A., Inc. [St]
- CTRMN001817-1860 1977 Report of the Council for Tobacco Research-U.S.A., Inc. [St]
- CTRMN001914-1967 1979 Report of the Council for Tobacco Research-U.S.A., Inc. [St]
- CTRMN001968-2025 1980 Report of the Council for Tobacco Research-U.S.A., Inc. [St]
- CTRMN002026-2088 Report of the Council for Tobacco Research-U.S.A., Inc. [St]
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- CTRMN002149-2223 Report of the Council for Tobacco Research-U.S.A., Inc. [St]
- CTRMN002224-2942 Application for Research Grant An Investigation of the Spectral and Chromatographic Characteristics of Aromatic Hydrocarbons. [Study on High Temperature Gas-Liquid Partition Chromatography]
- CTRMN002943-3303 [Regarding Polio and Tuberculosis As Predisposing Factor in Lung Cancer]
- CTRMN003304-3322 Tobacco-Health Research Program [Display Case Showing Main Areas of Investigation]
- CTRMN003323-3326 Statement of Policy Containing Conditions and Terms Under Which Project Grants Are Made [Rules for Approval of Grants Relating to Tobacco Use and Human Health]
- CTRMN003327-3337 A Brief Review of the Smoking-Lung Cancer Theory [Concerning Problems of Cigarette Lung Cancer Causation and Why They Have No Been Solved]
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- CTRMN003358-3365 Some Information About... The Council for Tobacco Research-U.S.A., Inc. ...and Its Research Program [Informs About the Purpose and Function of Organization's Research Program]
- CTRMN003366-3374 the Research Program of the Scientific Advisory Board to the Council for Tobacco Research - U.S.A. [Informs the Purposes, Policies, and the Research Program of the Board]
- CTRMN003375-3419 the Cancer-Smoking Controversy [Regards the Fallacious Conclusions of Cigarette Smoking Causing Lung Cancer From A Mathematical and Scientific Point of View]
- CTRMN003420-3425 Some Harvard Men & the Smoking Habit [Give Results of Questionnaire Relating to Biological Factors of Tobacco Smoking]
- CTRMN003426-3431 the Pathologic Anatomy of the Bronchial Tree and Lungs Reprinted From the Archives of Pathology Vol. 70 [St Finds of Equivocal Results with the Use of Tobacco]
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- CTRMN003438-3442 Some Statistical Observations on A Cooperative Study of Human Pulmonary Pathology, II [Results Show Pathological Lungs in Different Cities Are Acutally Different]
- CTRMN003443-3447 Some Statistical Observations on A Cooperative Study of Human Pulmonary Pathology. II [Study Comparing Pathological Conditions in 8 Different Cities Shows That Conditions Are All Different]
- CTRMN003448-3456 Some Statistical Observations on A Cooperative Study of Human Pulmonary Pathology [Systematic Examinations of the Conditions at Autopsy in the Bronchial Mucosae of Run-of-the-Mill Cases]
- CTRMN003457-3464 Some Statistical Observations on A Cooperative Study of Human Pulmonary Pathology III [When Probability Is Doubtful the Use of Variable Tables to Calculate Results Is the Best Way to Make A Precise and Accurate Answer for Sufficient Range of Pathological Conditions]
- CTRMN003465-3476 Differences Between Smokers and Nonsmokers [Differences Between Smokers and Nonsmokers Have to Do with Personality Traits and Physiologic Criteria]
- CTRMN003477-3485 the Psychology of Smoking [Smoking Is Determined by Certain Personality Variables and Personal Needs]
- CTRMN003486-3490 the Tobacco and Health Research Program of the Scientific Advisory Board [Regarding Information the Tobacco Industry Research Committee Do for the Research Program]
- CTRMN003491-3558 Tobacco Consumption in Various Countries [Results of Cigarette and Cigar Smokers From Different Countries]
- CTRMN003559-3560 Statement of Policy Containing Conditions and Terms Under Which Project Grants Are Made [Guidelines for Which Grants Are Approved]
- CTRMN003561-3780 Tobacco Smoking in the United States in Relation to Income Marketing Research Report No. 189 [A Report Compiled by the Bureau of the Census for the United States Public Health Service on Smoking Characteristics in Relation to Income, Age, Region, Urban-Rural Residence and Occupation.]
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- CTRMN003784-3787 Confidential Report on Meeting January 18, 1954 Tobacco Industry Research Committee (TIRC) [St]
- CTRMN003788-3797 Confidential Report on Meeting March 15, 1954 Tobacco Industry Research Committee [St]
- CTRMN003798-3800 Tobacco Industry Research Committee Meeting [St]
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- CTRMN003816-3835 Tobacco Industry Research Committee Meeting [St]
- CTRMN003836-3852 Tobacco Industry Research Committee Meeting November 3, 1955 [St]
- CTRMN003853-3869 Tobacco Industry Research Committee Meeting February 14, 1956 [St]
- CTRMN003870-3895 Tobacco Industry Research Committee Meeting October 9, 1956 [St]
- CTRMN003896-3907 Tobacco Industry Research Committee Meeting May 9, 1957 [St]
- CTRMN003908-3923 Tobacco Industry Research Committee Meeting November 8, 1957 [St]
- CTRMN003924-3931 Tobacco Industry Research Committee Meeting May 8 1958 [St]
- CTRMN003932-3939 Tobacco Industry Research Committee Meeting November 6, 1958 [St]
- CTRMN003940-3945 Tobacco Industry Research Committee Meeting [St]
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- CTRMN003983-3991 Tobacco Industry Research Committee Meeting [St]
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- CTRMN004053-4057 Minutes of of the Board of Directors January 28, 1972 [St]
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- CTRMN004071-4076 Minutes of the Meeting of the Board of Directors February 1, 1974 [St]
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- CTRMN004087-4091 Minutes of the Meeting of the Board of Directors January 31, 1975 [St]
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- CTRMN004142-4147 Minutes of the Special Meeting of the Board of Directors December 10, 1975 [St]
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- CTRMN004154-4157 Minutes of the Special Meeting of the Board of Directors September 9, 1976 [St]
- CTRMN004158-4161 Minutes of the Meeting of the Board of Directors January 28 1977 [St]
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- CTRMN004168-4172 Minutes of the Meeting of the Board of Directors January 29, 1979 [St]
- CTRMN004173-4176 Minutes of the Meeting of the Board of Directors February 1, 1980 [St]
- CTRMN004177-4178 Minutes of the Board of Directors Executive Committee Meeting New York, New York [St]
- CTRMN004179-4184 Minutes of the Meeting of the Directors January 30, 1981 [St]
- CTRMN004185-4189 Minutes of the Special Meeting of the Board of Directors June 25, 1981 [St]
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- CTRMN004401-4404 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004405-4409 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004410-4413 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004414-4416 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004417-4420 Confidential Report Scientific Advisory Board Meeting [St]
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- CTRMN004431-4433 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004434-4436 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004437-4439 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004440-4443 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004444-4446 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004447-4450 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004451-4454 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004455-4459 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004460-4463 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004464-4467 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004468-4472 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004473-4475 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004476-4480 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004481-4484 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004485-4492 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004493-4497 Confidential Report Scientific Advisory Board Meeting September 23-24, 1967 [St]
- CTRMN004498-4501 Confidential Report Scientific Advisory Board Meeting December 9-10, 1967 [St]
- CTRMN004502-4505 Confidential Report Scientific Advisory Board Meeting [St]
- CTRMN004506-4510 Confidential Report Scientific Advisory Board Meeting La Jolla, California March 2-3-4, 1968 [St]
- CTRMN004511-4516 Confidential Report Scientific Advisory Board Meeting New York New York May 25-26, 1968 [St]
- CTRMN004517-4522 Confidential Report Scientific Advisory Board Meeting New York, New York September 14-15, 1968 [St]
- CTRMN004523-4526 Confidential Report Scientific Advisory Board Meeting New York, New York December 8-9, 1968 [St]
- CTRMN004527-4531 Confidential Report Scientific Advisory Board Meeting New York, New York March 22-23, 1969 [St]
- CTRMN004532-4538 Confidential Report Scientific Advisory Board Meeting New York, New York May 16-18, 1969 [St]
- CTRMN004539-4544 Confidential Report Scientific Advisory Board Meeting New York, New York September 12-14, 1969 [St]
- CTRMN004545-4549 Confidential Report Scientific Advisory Board Meeting New York, New York December 12-14, 1969 [St]
- CTRMN004550-4555 Confidential Report Scientific Advisory Board Meeting Colorado Springs, Colorado March 20-22, 1970 [St]
- CTRMN004556-4560 Confidential Report Scientific Advisory Board Meeting New York, New York [St]
- CTRMN004561-4569 Confidential Report Scientific Advisory Board Meeting New York, N.Y. September 18-19-20, 1970 [St]
- CTRMN004570-4578 Confidential Report Scientific Advisory Board Meeting Chicago, Illinois January 15,16, 1971 [St]
- CTRMN004579-4585 Confidential Report Scientific Advisory Board Meeting New York, N.Y. May 7-8-9, 1971 [St]
- CTRMN004586-4593 Confidential Report Scientific Advisory Board Meeting New York, N.Y. September 24-25-26, 1971 [St]
- CTRMN004594-4598 Confidential Report Scientific Advisory Board Meeting New York, N.Y. [St]
- CTRMN004599-4604 Confidential Report Scientific Advisory Board Meeting Palm Springs, California March 24-25-26, 1972 [St]
- CTRMN004605-4609 Confidential Report Scientific Advisory Board Meeting New York, New York June 9-11, 1972 [St]
- CTRMN004610-4614 Confidential Report Scientific Advisory Board Meeting New York, New York September 15-17, 1972 [St]
- CTRMN004615-4623 Confidential Report Scientific Advisory Board Meeting New York, New York March 14-15-16, 1973 [St]
- CTRMN004624-4626 Meeting Executive Committee of the Scientific Advisory Board June 13, 1973 New York, N.Y. [St]
- CTRMN004627-4634 Confidential Report Scientific Advisory Board Meeting New York, New York October 10-11-12, 1973 [St]
- CTRMN004635-4643 Meeting Executive Committee of the Scientific Advisory Board December 4, 1973 New York, N.Y. [St]
- CTRMN004644-4654 Confidential Report Scientific Advisory Board Meeting New York, New York October 30-31 November 1, 1974 [St]
- CTRMN004655-4656 Meeting Executive Committee of the Scientific Advisory Board December 13, 1974 New York, N.Y. [St]
- CTRMN004657-4664 Confidential Report Scientific Advisory Board Meeting Santa Barbara, California March 26-27-28, 1975 [St]
- CTRMN004665-4672 Confidential Report Scientific Advisory Board Meeting New York, New York September 10-11-12, 1975 [St]
- CTRMN004673-4675 Meeting Executive Committee of the Scientific Advisory Board New York, New York December 13, 1975 [St]
- CTRMN004676-4683 Confidential Report Scientific Advisory Board Meeting Santa Barbara, California March 17-18-19, 1976 [St]
- CTRMN004684-4686 Meeting of the Executive Committee of the Scientific Advisory Board New York, New York June 11, 1976 [St]
- CTRMN004687-4694 Confidential Report Scientific Advisory Board Meeting New York, New York September 28-29-30, 1976 October 1, 1976 [St]
- CTRMN004695-4697 Meeting of the Executive Committee of the Scientific Advisory Board Bethesda, Maryland December 1, 1976 [St]
- CTRMN004698-4706 Confidential Report Scientific Advisory Board Meeting Tuscon, Arizona March 23-25, 1977 [St]
- CTRMN004707-4708 Meeting of the Executive Committee of the Scientific Advisory Board Tuscon, Arizona March 25, 1977 [St]
- CTRMN004709-4710 Meeting of the Executive Committee of the Scientific Advisory Board New York, New York May 19, 1977 [St]
- CTRMN004711-4719 Confidential Report Scientific Advisory Board Meeting New York, New York October 26-28, 1977 [St]
- CTRMN004720-4723 Confidential Report Scientific Advisory Board Meeting Phoenix, Arizona January 16-17, 1978 [St]
- CTRMN004724-4724 Confidential Report Meeting of the Scientific Advisory Board Committee Phoenix, Arizona January 17, 1978 [St]
- CTRMN004725-4734 Confidential Report Scientific Advisory Board Meeting New York, New York April 26-27-28, 1978 [St]
- CTRMN004735-4735 Confidential Report Scientific Advisory Board Executive Committee New York, New York April 27, 1978 [St]
- CTRMN004736-4737 Confidential Report Meeting for the Scientific Advisory Board New York, New York July 27, 1978 [St]
- CTRMN004736A-4736A Confidential Report Meeting of the Scientific Advisory Board New York, New York July 27, 1978 [St]
- CTRMN004738-4747 Confidential Report Scientific Advisory Board Meeting New York, New York October 18-19-20, 1978 [St]
- CTRMN004748-4750 Confidential Report Meeting of the Scientific Advisory Board New York, New York December 20, 1978 [St]
- CTRMN004751-4759 Confidential Report Scientific Advisory Board Meeting New York, New York April 11-12-13, 1979 [St]
- CTRMN004760-4769 Confidential Report Scientific Advisory Board Meeting New York, New York October 17-18-19, 1979 [St]
- CTRMN004770-4770 Confidential Meeting of the Report Scientific Advisory Board New York, New York October 18, 1979 [St]
- CTRMN004771-4780 Confidential Report Scientific Advisory Meeting New York, New York Aprill 9-10-11, 1980 [St]
- CTRMN004781-4781 Confidential Report Executive Committee of the Scientific Advisory Board Meeting New York, New York June 20, 1980 [St]
- CTRMN004782-4783 Confidential Report Executive Committee of the Scientific Advisory Board Meeting New York, New York September 16, 1980 [St]
- CTRMN004784-4792 Confidential Report Scientific Advisory Board Meeting New York, New York October 8-9-10, 1980 [St]
- CTRMN004793-4794 Confidential Report Meeting of the Scientific Advisory Board New York, New York October 9, 1980 [St]
- CTRMN004795-4804 Confidential Report Scientific Advisory Board Meeting New York, New York April 8-9-10, 1981 [St]
- CTRMN004805-4805 Confidential Report Meeting of the Executive Committee of the Scientific Advisory Board New York, New York April 8, 1981 [St]
- CTRMN004806-4806 Confidential Report Meeting of the Scientific Advisory Board New York, New York September 10, 1981 [St]
- CTRMN004807-4816 Confidential Report Scientific Advisory Board Meeting New York, New York October 14-15-16, 1981 [St]
- CTRMN004817-4818 Confidential Report Meeting of the Executive Committee Scientific Advisory Board New York, New York October 15, 1981 [St]
- CTRMN004819-4820 Confidential Report Meeting of the Executive Committee of the Scientific Advisory Board New York, New York December 9, 1981 [St]
- CTRMN004821-4831 Confidential Report Scientific Advisory Board Meeting New York, New York April 21, 22, 23, 1982 [St]
- CTRMN004832-4833 Confidential Report Meeting of the Executive Committee of the Scientific Advisory Board New York, New York June 21, 1982 [St]
- CTRMN004834-4843 Confidential Report Scientific Advisory Board Meeting New York, New York October 6,7,8, 1982 [St]
- CTRMN004844-4844 Confidential Report Meeting of the Executive Meeting of the Scientific Advisory Board New York, New York October 8, 1982 [St]
- CTRMN004845-4845 Confidential Report Meeting of the Executive Committee of the Scientific Advisory Board Scottsdale, Arizona February 24, 1983 [St]
- CTRMN004846-4857 Confidential Report Scientific Advisory Board Meeting New York, New York April 20, 21, 22, 1983 [St]
- CTRMN004858-4858 Confidential Report Meeting of the Executive Committee of the Scientific Advisory Board New York, New York April 22, 1983 [St]
- CTRMN004859-4859 Confidential Report Meeting of the Executive Committee of the Scientific Advisory Board New York, New York June 6, 1983 [St]
- CTRMN004860-4871 Confidential Report Scientific Advisory Board Meeting New York, New York October 12, 13, 14, 1983 [St]
- CTRMN004872-4882 Confidential Report Scientific Advisory Board Meeting New York, New York March 28, 29, 30, 1984 [St]
- CTRMN004883-4883 Confidential Report Meeting of the Executive Committee of the Scientific Advisory Board New York, New York March 29, 1984 [St]
- CTRMN004884-4895 Confidential Report Scientific Advisory Board Meeting September 19, 20, 21, 1984 New York, New York [St]
- CTRMN004896-4896 Confidential Report Meeting of the Executive Committee of the Scientific Advisory Board New York, New York September 20, 1984 [St]
- CTRMN004897-4897 Confidential Report Meeting of the Executive Committee of the Scientific Advisory Board Palm Beach, Florida February 25, 1985 [St]
- CTRMN004898-4898 Confidential Report Meeting of the Executive Committee of the Scientific Advisory Board New York, New York April 16, 1985 [St]
- CTRMN004899-4910 Confidential Report Scientific Advisory Board Meeting April 15, 16, 17, 1985 New York, New York [St]
- CTRMN004911-4911 Confidential Report Meeting of the Executive Committee of the Scientific Advisory Board New York, New York April 16, 1985 [St]
- CTRMN004912-4923 Confidential Report Scientific Advisory Board Meeting April 15, 16, 17, 1985 New York, New York [St]
- CTRMN004924-4927 for Release: A.M.'s Wednesday, April 14, 1954 ["Reaction to the Compendium "A Scientific Perspective on the Cigarette Controversy""]
- CTRMN004928-4929 for Release: A.M.'s Tuesday, April 27, 1954 [Scientific Advisory Board Organized Early to Begin Research Into All Phases of Tobacco Use and Health for the Year]
- CTRMN004930-4931 for Release in A.M.'s of Tuesday, May 18, 1954 [Proposals Submitted for Cancer Research Projects for Consideration by Scientific Advisory Board]
- CTRMN004932-4933 for Release After 10:30 A.M., June 15, 1954 [Appointment of Dr. Clarence Cook Little Announced by the Tobacco Research Industry Committee]
- CTRMN004934-4937 for Immediate Release [American Cancer Society Survey Conveys the Need to Further Research to Discover Cause of Cancer and Cardiovascular Disease]
- CTRMN004938-4939 for Release in Am's of Tuesday, July 20, 1954 [Edwin B. Wilson of Harvard University Became A Member of Scientific Advisory Board of the Tobacco Industry Research Committee]
- CTRMN004940-4942 for Release: A.M.'s of Wednesday, July 28, 1954 Little Announces Research Policy of Tobacco Industry Research Committee [Three Main Areas to Be Covered by Research Program Announced]
- CTRMN004943-4944 for Release in A.M.'s Thursday, August 19, 1954 [Dr. Julius H. Comroe of University of Pennsylvania, Accepted Membership on Scientific Advisory Board of the Tobacco Industry Research Committee]
- CTRMN004945-4945 for Immediate Release (Monday, October 11, 1954) Dr. Little Gives TIRC View [Little States That No Convincing Evidence Has Yet Been Found to Prove That Cigarette Smoking Causes Lung Cancer]
- CTRMN004946-4946 for Immediate Release (Tuesday, October 12, 1954) [Timothy V. Hartnet, Chairman of Board, Stated That Public Should Be Reminded That No Lung Cancer Causing Agent Has Yet Been Identified in Tobacco]
- CTRMN004947-4947 for Release: Wednesday, October 20, 1954 Hartnett Approves Care in Research [Committee to Be Sure That Reliable Evidence Is Available Before Announcing Important Conclusions to the Public About Smoking]
- CTRMN004948-4948 for Immediate Release (Thursday, October 21, 1954) Hartnett Comments on Cigarette Paper Burning [Timothy V. Hartnett Comments That A Cancer Causing Compound on Skin of Mice Has Been Produced by Burning Cigarette Paper Under Certain Lab Conditions]
- CTRMN004949-4952 for Release: A.M.'s, Monday, November 8, 1954 Tobacco Industry Research Committee Announces Initial Grants [Six Scientific Research Grants Totalling Over $82,000 Made Public]
- CTRMN004953-4954 for Release in A.M.'s, Monday, December 6, 1954 Scientific Associate Named by Tobacco Research Group [Robert C. Hockett Appointed As Scientific Director of TIRC to Help Develop Research Into Tobacco Use and Health]
- CTRMN004955-4956 for Immediate Release Cross-Country Lung Study Planned by Tobacco Group [Group of Pathologists Plan A Cooperative Study to Increase Knowledge of Lung Ailments]
- CTRMN004957-4959 for Release in Year-End Editions But Not Before December 27, 1954 Statement by Timothy V. Hartnett, Chairman Tobacco Industry Research Committee [TIRC Will Approve A Quarter of A Million Dollars for Research Into Public Health Problems by the End of 1954]
- CTRMN004960-4963 for Release: Monday A.M.'s, January 17, 1955 Tobacco Industry's New Research Grants Send Total to More Than $300,000 [New Research Grants Announced by TIRC to Relate to Both Human and Animal Scientific Studies]
- CTRMN004964-4966 for Release in A.M.'s of Friday, April 8, 1955 Tobacco Industry Group Votes Medical Research Fellowships [TIRC Announced Fellowship Program to Create Interest in Research Among Medical School Students]
- CTRMN004967-4969 Release Tuesday, May 17, 1955 and Thereafter Tobacco and Health Studies Cover Wide Range of Research [Although No Scientific Proof That Cigarettes or Air Pollution Cause Lung Cancer, Progress Is Being Made to Learn More About Tobacco Use and Health by the TIRC]
- CTRMN004970-4972 Tobacco Research Grants Increased to 490,000 Mark [Research Grants Are Created So Science Can Provide An Answer to Public Health Problems]
- CTRMN004973-4973 Hartnett Comments on Auerbach Paper [Many Studies on Human Lung Tissue, Not Enough Data Available to Draw A Conclusion Yet]
- CTRMN004974-4975 Anti-Smoking Theories Not Based on Complete Scientific Knowledge [Scientific Investigation Into What the Real Effects Are From Tobacco Use]
- CTRMN004976-4977 Hartnett Comments on Statistical Study [Research Intensified in Past Year, No Proof That Smoking Causes Cancer]
- CTRMN004978-4980 Doctor's Survey Termed 'biased, 'says Hartnett [Questionnaire Would Give No Concrete Conclusions About Tobacco Causing Cancer]
- CTRMN004981-4982 Hartnett Alerts Burley Men to Challenge Tobacco Attacks [Doctors Are Expressing Their Doubts About Statements Already Made; Tobacco Effects]
- CTRMN004983-4984 Bright Belt Warehouse Men Told Facts Challenge Critics [Still Looking for Proof That Tobacco Causes Cancer]
- CTRMN004985-4986 Tobacco Spokesman Says Facts and Position Are Unchanged [Various Experiments with Animals Showed That Cancer Was Not the Outcome From Tobacco Smoke]
- CTRMN004987-4987 Hartnett Comments on Statistical Study [Methods Used for Cancer Research Still Do Not Give Enough Information]
- CTRMN004988-4990 British Tobacco Experiments Unable to Induce Cancers [Still No Connection, Tests Will Continue]
- CTRMN004991-4993 Tobacco Research Grants Now Over 838,000 Mark [Tobacco Research Is Getting More Support From Doctors, Scientists, and Educators]
- CTRMN004994-4996 Statement by Timothy V. Hartnett, Chairman Tobacco Industry Research Committee [Summary of the Past Years' Events in Tobacco Research]
- CTRMN004997-4999 Tobacco Research Fund Raised to 1,500,000 [Finding New Ways to Break Down Tobacco]
- CTRMN005000-5001 Tobacco Industry Group Renews Medical Research Fellowships [More Medical Students Are Receiving Fellowships Than Last Year]
- CTRMN005002-5003 Hartnett Statement on Cancer Meeting Reports [There Is Still Much Research to Be Done Before Tobacco Is Linked to Cancer]
- CTRMN005004-5005 [Pathologists From Around the Country Have Studied Human Lung Tissues Over the Past Year]
- CTRMN005006-5006 [Smoking Patterns Do Not Explain Differences in Lung Cancer]
- CTRMN005007-5008 Hartnett Cites British Tobacco Tests Failing to Produce Animal Cancer [the Search for Cancer Must Be Broadened and Intensified]
- CTRMN005009-5010 Hartnett Comments on Statistical Claims [Although Many Believe Smoking Causes Cancer, Scientists Still Have Not Found Any Prof]
- CTRMN005011-5011 [Present Knowledge Doesn't Hint A Relationship Between Smoking and Heart Problems]
- CTRMN005012-5016 Hartnett Comments on Cancer Society Booklet [Pamphlet Omits Some Important Research Results]
- CTRMN005017-5018 Statement by Timothy V. Hartnett, Chairman Tobacco Industry Research Committee [Research Committee Needs More Scientific Investigation]
- CTRMN005019-5025 Tobacco Research Funds Reach 2.2 Million Mark [Over 60 Independent Scientists Throughout the Country Are Working in Institutions to Further the Research of Cancer and Tobacco Use, They Are Listed]
- CTRMN005026-5027 Hartnett Comments on French Report [French Are Reporting Rapid Cancer Formation in Mice, Hartnett Feels It Can't Be Judged on the Basis of New Reports Without Longer Consideration and Careful Analysis]
- CTRMN005028-5030 Harnett Cites Points for Clarification in Tobacco Health Study [Smoking Study Reached the Public's Attention Before It Was Reviewed and Before the Facts Were Made Crystal Clear]
- CTRMN005031-5032 Hartnett Comments on Wynder News Stories [News Story Claims That Assumptions Have Been Made About Mouse Skin Painting Experiments]
- CTRMN005033-5037 Statement on Smoking and Health Studies [Scientists Are Developing A Program for Different Phases of Tobacco Use and Health, Members Listed]
- CTRMN005038-5045 Hartnett Says Statistics Do Not Establish Causes [Studies Are Open to Assumptions and Certain Selection of Subjects]
- CTRMN005046-5048 Hartnett Cites Scientists Doubting Smoking-Cancer Theory [the Surgeon General Believes the Studies Are Missing Essential Facts That Should Be Acknowledged]
- CTRMN005049-5050 Scientist Comments on Benzpyrene Report [Benzpyrane in Tobacco Smoke, Under Investigation for Years Caused Cancer in Lab Animals But Not Humans]
- CTRMN005051-5055 "Cancer Researcher Challenges "Cause and Effect" Charges Against Smoking" [It's Difficult to Have A Cause and Effect Relationship When Dealing with Cancer and Tobacco Use]
- CTRMN005056-5056 [Atlantic Monthly Gives A Misleading Picture of Dr. Little and His Public Position]
- CTRMN005057-5058 Tobacco Committee Chairman Comments on Cancer Society Talk [Many Unresolved Questions About Tobacco Causing Cancer Don't Stop Researching]
- CTRMN005059-5061 Tobacco Research Scientist Discusses Smoking Question [Most Tend to Believe the Anti-Cigarette Theory But It Shouldn't Be Confused with the Facts There's Still Not Enough Facts to Prove That Smoking Causes Cancer]
- CTRMN005062-5062 Hartnett Says Leaflet Admits Differing Opinions on Smoking [Leaflet Tells How Scientists Disagree on Evidence]
- CTRMN005063-5066 Research Program Throws Doubts on Smoking Charges [Incorrect Claims and Harmful Effects From Tobacco]
- CTRMN005067-5069 Statement by Timothy V. Hartnett, Chairman Tobacco Industry Research Committee [More and More Scientists Had Doubts and Disbeliefs in the Charges Against Smoking As A Cause of Cancer]
- CTRMN005070-5071 Tobacco Research Scientist Discusses Smoking Question [Scientists Say Smoking Has Been Proved Guilty When Linked with Human Health Problems]
- CTRMN005072-5072 Pamphlet Merely Review, Dr. Little Says [Opinions Is All the Author Gives in His Pamphlet Scientists Are Still Disputing]
- CTRMN005073-5076 TIRC Fund for Research Boosted to $2,700,000 [Grants for Independent Scientists Interested in Studying Problems of Cancer and Heart Disease When Related to Smoking]
- CTRMN005077-5080 [New Knowledge on Smoking and Health Questions]
- CTRMN005081-5081 [Veterans Study of Smoking Habits]
- CTRMN005082-5082 [Report on How There Was Existing Research Evidence and How It Was Ignored]
- CTRMN005083-5085 [Regarding Anti-Tobacco Movement]
- CTRMN005086-5086 [Benzpyrene in Cigarette Smoke]
- CTRMN005087-5088 [Experimental Evidence Is Weak]
- CTRMN005089-5089 Hartnett Says Article on Arsenic Goes Beyond Facts [Farmers Use of Insecticides with Arsenicals on Growing Tobacco Has Steadily Been Declining]
- CTRMN005090-5091 [Scientists Who Produce Conflicting Results Are Being Ignored by the Health Department]
- CTRMN005092-5094 Statement by Timothy V. Hartnett, Chairman Tobacco Industry Research Committee [Even More Grants Have Been Made Available More Factors Have Been Associated with Lung Cancer]
- CTRMN005095-5100 Tobacco Industry Group Announces Research Grants [Grant Increases to $3,200,000 List of Grants Announced]
- CTRMN005101-5103 Tobacco-Health Research Described in 1958 Report [the Report Talked About Experiments That Were Unable to Produce Cancer and the Cause and Effect Theory]
- CTRMN005104-5104 [Report Shows That Other Factors Besides Smoking Have Been Causing Lung Cancer, But Scientists Do Not Dismiss the Fact That Lung Cancer Is Possibility From Smoking]
- CTRMN005105-5105 [Anti-Smoking Campaign Is Thought to Be A One-Sided Propaganda Effort]
- CTRMN005106-5106 [Questions Arise From on-Sided Study]
- CTRMN005107-5111 Cancer Scientist's Comments on Smoking-Lung Cancer Review [Evidence on Smoking and Lung Cancer Is Accumulating, Among Other Contributing Factors]
- CTRMN005112-5117 [Comments Relating to Observation on Various Studies]
- CTRMN005118-5122 Research Grants Announced by Tobacco Industry Group [$500,000 Was Added to Research Funds, A List of Recipients with the New Grants Is Mentioned]
- CTRMN005123-5127 Research Supported by Tobacco Committee Discussed in Scientific Director's Report [It Seems That Finding An Answer to Lung Cancer and Cardiovascular Diseases Are Too Complicated]
- CTRMN005128-5128 [Attacks on Tobacco, the Lung Cancer Issue Is Still Not Settled]
- CTRMN005129-5129 Nta Stand on Smoking Repeats Opinions [Statement Gives No Evidence and Is Dealing Mainly with Opinions]
- CTRMN005130-5132 Tobacco Research Group Adds New Scientific Associate [New Scientific Director Was Added to the TIRC, Curriculum of J. Morrison Brady]
- CTRMN005133-5134 Tobacco Research Group Cites Questions Raised in Heart Statement [Lack of Evidence Proposes New Questions and Doubts About Cardiovascular Disease]
- CTRMN005135-5137 New Evidence Shows Complexities of Lung Cancer, Scientist Says [Hundreds of Studies Indicate Many Factors Contribute to the Complex Chain That May Result in Lung Cancer, No One Can Figure Out the Right Factor and Still the Reported Lung Cancer Cases Are Rising]
- CTRMN005138-5140 New Grants to Scientists Made by Tobacco Research Group [Research Grants Totalling $523,000 Made to 40 Scientists This Year]
- CTRMN005141-5144 Cancer Research Opens Up New Areas, Extra Funds Appropriated for Study [TIRC Stepping Up Financial Support of Independent Health Research]
- CTRMN005145-5147 Scientists in 11 States Get Research Grants for Tobacco-Health Studies [17 Research Grants Totaling Nearly $200,00 Awarded to Scientists in 11 States for Studies of Tobacco Use and Health]
- CTRMN005148-5151 New Direction for Tobacco-Health Research in '61, Says Chairman of Tobacco Industry Research Committee [Future Research to Concentrate on How Lung Cancer and Heart Disease Originate]
- CTRMN005152-5160 Research on Smoking and Health Discussed by Scientific Advisory Board to T.I.R.C. [Health Research Expansion Called for in 22 Specific Areas]
- CTRMN005161-5162 Scientist Reports on Research Progress As T.I.R.C. Boosts Funds to $4,650,000 [Dr. Clarence Cook Little Proposed Steps for Medical Research]
- CTRMN005163-5163 Nation's Medical Students Offered Research Fellowships by Tobacco Research Group [Program Designed to Encourage Research As A Career]
- CTRMN005164-5168 Scientists in 14 States Get Research Grants for Tobacco-Health Studies [Fifteen Grants for New Research Announced]
- CTRMN005169-5173 Tobacco Industry Research Committee Adds $800,000 for New Research [Emphasis Put on Viruses, Bioassay, Psychological and Physiological Research]
- CTRMN005174-5176 ""Significant Developments" in Cancer Research Reviewed in Annual Report by Dr. C.C. Little" [Scientific Findings of the Past Year Reviewed]
- CTRMN005177-5179 Tobacco Research Group Offers Fellowships to Medical Students to Spur Interest in Research Work [Program Designed to Encourage Career in Research]
- CTRMN005180-5180 Tobacco Research Committee Chairman Comments on Mouse Skin Painting [Harmless Everyday Substances Can Cause Cancer in Laboratory Animals]
- CTRMN005181-5182 Smoking-Health Situation Calls for Facts, Not Emotions, Says Hartnett [Repetition Does Not Add to Scientific Knowledge]
- CTRMN005183-5217 Smoking-Health Situation Calls for Facts, Not Emotions, Says Hartnett [Repetition Does Not Add to Scientific Knowledge]
- CTRMN005218-5224 52 Additional Research Grants Made by Tobacco Industry Group [Money for Studies Designed to Give New Leads to Lung Cancer and Other Health Problems]
- CTRMN005225-5225 Medical Student Fellowships Offered by Tobacco Research Group [Program to Encourage Research]
- CTRMN005226-5228 Gaps Still Exist in Knowledge of Lung Cancer and Heart Disease, Says Little [Multiple Factors and Influences That Contribute to Lung Cancer Unknown]
- CTRMN005229-5230 Scientific Director of Tobacco Industry Research Committee Comment on Resolution by American Heart Association [TIRC Welcomes Recognition of Need for Further Research to Determine Full Facts About Smoking]
- CTRMN005231-5234 Tobacco Committee Adds $1 Million for Continuing Research Studies [Scientific Advisory Board Assured TIRC Will Provide More Funds]
- CTRMN005235-5235 [Scientific Director of TIRC Sent Telegrams to the Surgeon General and the President of the Ama]
- CTRMN005236-5236 [Ama Supports Research on Tobacco and Health]
- CTRMN005237-5239 [TIRC Renamed and Reorganized]
- CTRMN005240-5241 Dr. Howard B. Andervont Named to the Scientific Advisory Board [Editor of the Journal of the National Cancer Institute Appointed]
- CTRMN005242-5277 Tobacco Industry Group Awards $817,165 for Health Research [37 Additional Research Grants Have Been Awarded by the Ctr]
- CTRMN005278-5282 Scientific Director C.C. Little Reports Decade of Tobacco-Health Research [Findings on What Diseases Smoking Can Cause]
- CTRMN005283-5286 Council Awards $500,000 for Tobacco and Health Research [Number of Grants Awarded for Tobacco Use and Health Research]
- CTRMN005287-5291 Summary of the Testimony of Clarence C. Little Before the Senate Commerce Committee [Discussion on Cancer and How It Affects Our Bodies]
- CTRMN005292-5319 Council Awards $514,767 for Tobacco and Health Research [Number of Grants Awarded to Scientist Over the Period of 10 Years]
- CTRMN005320-5348 Tobacco - Health Studies Reviewed in Annual Report [Discussion on Cigarette Smoking Being Helpful with Causing Diseases in Smokers]
- CTRMN005349-5367 Tobacco and Health Research Awards Pass $9 Million Total [Grants Given to Scientist Studying Matter Related to Tobacco Use and Health]
- CTRMN005368-5375 Tobacco-Health Research Grants Awarded New York Scientists [Scientists Approved to Continue Research on Lung Cancer and Other Diseases]
- CTRMN005376-5382 Tobacco - Health Studies Reviewed in Annual Report [Studies of the Respiratory System in Experimental Animals and Human Patients Especially on Causes of Pulmonary Cancers]
- CTRMN005383-5384 [Opinions of Scientists That There Is No Relationship Between Smoking and Disease]
- CTRMN005385-5387 New Tobacco-Health Research Grants Total $2 Million [Number of Approved Grants for Studies on Tobacco Use and Health]
- CTRMN005388-5388 Furst Becomes Consultant to Tobacco Research Council [Dr. Furst Advise to Council on Programs Sponsored by Them]
- CTRMN005389-5393 Studies Raise Questions About Smoking As Health Hazard [Numerous Studies Done to Show What Effect Smoking Had on Our Health]
- CTRMN005394-5400 Broad Review of Tobacco-Health Picture Covered in Dr. Little's Latest Report Lung Cancer, Heart Disease, Chronic Pulmonary Ailments Are Complex in Nature, Says Noted Researcher Genetic and Environmental Factors May Be Involved Reports Scientific Director of Council for Tobacco Research [Recent Research Finding on Lung Cancer, Heart Disease and Chronic Pulmonary Ailments]
- CTRMN005401-5404 Significant Smoking-Health Finding Covered in Report by Dr. C.C. Little [Findings From Independent Scientists on Smoking and Health]
- CTRMN005405-5408 New Tobacco-Health Grants Announced; One Helps Revive Framinghan Heart Study [Awards Granted to Independent Scientists Researching Tobacco and Health]
- CTRMN005409-5412 New Scientific Findings About Cancer, Heart Disease, the Lung, Other Areas, Reported by Council for Tobacco Research [New Findings From Independent Scientists Relating to Tobacco and Health Issue]
- CTRMN005413-5415 New Smoking-Health Studies Boost Total to $23-Million [Council Awards More Grants to the Study of Lung Cancer, Viruses and Cancer, Heart Disease, and Chronic Pulmonary Ailments]
- CTRMN005416-5418 Progress in Tobacco-Health Research Achieved: Machines That Simulate Human Smoking [Machines to Help Scientists Effectively Study Smoke and Health Issues]
- CTRMN005419-5421 Noted Cancer Scientist Named Scientific Director of the Council for Tobacco Research [Dr. Hockett Who Was Acting Scientific Director Got Promoted to Research Director]
- CTRMN005422-5425 Massive Cancer Study Using Made-to-Order Mice [Study Using Mice to See If Human Lung Cancer Can Be Induced Regularly]
- CTRMN005426-5427 Tobacco Research Group Announces New Studies [12 New Studies Have Been Funded to Study Generic Factors in Lung Cancer and Emphysema and the Possible Influence of Nicotine on Fetal Growth]
- CTRMN005428-5429 Studies of Twins Expanded by Tobacco Research Group [Human Twins Used for Study to Determine Effects of Environment Agents on Various Diseases]
- CTRMN005430-5432 News About Smoking and Health Study Interaction of Genetic and External Influences in Lung Cancer [Studies Show That Only Minority of Smokers Get Lung Cancer Therefore Lung Cancer May Be Caused by Genetic Characteristics or External Influences Which People Have Been Exposed]
- CTRMN005433-5434 New Smoking and Health Grants Made by Tobacco Research Council [New Studies Have Received Grants to Continue Researching on Smoking and Health]
- CTRMN005435-5435 Yeaman Assumes Leadership of Council for Tobacco Research [Addison Yeaman Succeeds H.H. Ramm for Chairman and President of the Council for Tobacco Research]
- CTRMN005436-5438 14 New Studies Funded by Tobacco Research Council [Grants Awarded to Studies for Inhibition of Cancer by Different Chemicals, the Influence of Nicotine on Pregnancy and the Effects of Cigarette Smoke on the Body's Disease Fighting System]
- CTRMN005439-5441 Progress Being Made in Research on Emphysema [Scientist Discover Ways to Help Defend Against Emphysema]
- CTRMN005442-5444 14 New Smoking-Health Projects Are Approved [Recent Research Studies Dealing with Smoking and Health Have Been Given Grants]
- CTRMN005445-5446 Grants Awarded for New Smiking-Health Studies [Scientists Were Approved for Studying of Certain Enzymes in Human Lung Cancer and Emphysema]
- CTRMN005447-5448 Tobacco Research Report Discusses Heart Disease [Studies Have Found Progressive Atherosclerosis Rank First As Number One As Causes of Death From Cardiovascular Disease]
- CTRMN005449-5451 Grants Awarded for New Smoking-Health Research [New Studies Have Been Approved for Marker Substance That May Indicate Presence of Lung Cancer and on Smoking and Pregnancy]
- CTRMN005452-5453 Tobacco Research Group Funds New Smoking-Health Projects [A New Study for Relationship of Childhood Respiratory Disease to the Development of Adult Chronic Lung Disease]
- CTRMN005454-5455 Tobacco Research Group Reports... Funds for Smoking-Health Studies Pass $46,000,000 [Amount Council Has Given to Scientist for Research]
- CTRMN005456-5458 $5.9 Millions Given for Smoking-Healths Studies [Council Has Given Millions Over the Years to Researchers]
- CTRMN005459-5460 Tobacco Research Group Says... Continued Research Needed to Find Causes of Cancer and Other Major Diseases [Council Pledges to Continue to Give Financial Support to Scientists Studying Smoke-Health Issues]
- CTRMN005461-5462 $6 Million Granted for Smoking-Health Studies [Millions Given to Scientist for Further Study]
- CTRMN005463-5465 Tobacco Research Group Continues Funding for Independent Scientists [Council Has Provided Millions Over the Years to Researchers and Will Continue to Do So]
- CTRMN005466-5467 $5.5 Million Given for Smokin-Health Studies [Council Has Given Millions to New and on Going Studies Over the Years]
- CTRMN005468-5469 Annual Report Issued by Tobacco Research Group [Over 1.5882 Reports From Scientists Acknowledging Support From the Council Have Been Published]
- CTRMN005470-5473 $6 Million Awarded for 34 New Smoking-Health Studies [Millions Were Given to Scientists with New Studies and Continuing Ones From the Council]
- CTRMN005474-5474 Ctr's Latest Report Sets Abstract Record [More Reports Were Published From Scientists Acknowledgingg Support From Council for Tobacco Research Than Any Other Report Published in the Past]
- CTRMN005475-5475 Scientists Show... Growing Interest in Doing Smoking and Health Studies [Growing Number of Application Have Gone to the Council of Tobacco Research for Funding on Smoke Related Diseases]
- CTRMN005476-5479 $7 and A Half -Million Awarded for Smoking-Health Research [Millions Given to Scientists for Studying Lung Disease]
- CTRMN005480-5481 Council for Tobacco Research Announces... Hoyt and Hockett Retire After 30 Years: Gertenbach Is Named New President [Introduction to President of the Council for Tobacco Research]
- CTRMN005482-5482 Ctr's Annual Report Sets Abstract Record [the Number of Reports Acknowledging Support by the Council of Tobacco Research Is More Today Than It Was Years Ago]
- CTRMN005483-5485 Findings Published on Cigarette Smoke Inhalation Study with Mice [Results From Study Show That Smoke Did Not Produce Any Squamous Cell Lung Cancer]
- CTRMN005486-5525 Statement of Dr. Clarence Cook Little, Scientific Director, Tobacco Industry Research Committee, at Press Conference, University Club, New York City, June 15, 1954 [Regarding Relationship Between Lung Cancer and Tobacco]
- CTRMN005526-5533 "Transcript of Edward R. Murrow's First Tv Show on "Cigarettes and Lung Cancer"" [Regarding Experiments That Show That Cigarette Smoking Increases Chances for Lung Cancer]
- CTRMN005534-5541 "Transcript of Edward R. Murrow's Second Tv Show on "Cigarettes and Lung Cancer"" [Regarding Issue That Cigarette Smoke Does Not Cause Lung Cancer]
- CTRMN005542-5562 the Lung Cancer Problem and the Research Program of the Tobacco Industry Research Committee [Regarding Continuation of Study Dealing with Tobacco and Health]
- CTRMN005563-5573 A Report of Progress [Results From the Study of Smoking and Health Issue Will Greatly Depend on Well Planned and Well-Executed Scientific Research]
- CTRMN005574-5585 Tobacco and the Cardiovascular System the Program of the Tobacco Industry Research Committee [Program Strives to Discover Facts and Relationships Described with Objectivity]
- CTRMN005586-5597 A Search for Facts [Regarding Information Needed to Be Gathered on Smoking and Health Problems to Defend Industry]
- CTRMN005598-5605 the Lung Cancer Problem and the Research Program of the Tobacco Industry Research Committee [Discussion on Different Studies Will Continue to Be Made Until A Answer Is Found]
- CTRMN005606-5607 Cancer Research Guest Editorial Smoking and Lung Cancer Volume 16 [St Regarding Support Given to Scientist for Research]
- CTRMN005608A-5609 "Correspondence Regarding "Smoking and Health"" [Discussion on Researching on Tobacco and Health with Objectivity and Not Be Judgmental]
- CTRMN005608B-5609 Hypfibrinogenemia [Regarding Transfusions and Clotting Mechanism in A Case of Extraordinarily Delayed Post-Partum Hemorrhage]
- CTRMN005608C-5609 Diabetic Children [Admitting Omission of Different Data From Other Sources]
- CTRMN005608D-5609 Revocation of Licenses [Revoking of Registration From Dr. Louis A. Scinta]
- CTRMN005610A-5613 Mayo Clinic Head Believes Smoking Not Cancer Cause Tobacco and Health Volume 1 Number 1 [Smoking Not Believed to Be Cause of Lung Cancer, According to Some Noted Physicians]
- CTRMN005610B-5613 Six Experts State Doubts on Smoking-Cancer Theory Tell Congressmen Reasons for Position Tobacco and Health Volume 1 Number 1 [Reasons for Not Accepting Theory That Smoking Causes Lung Cancer]
- CTRMN005610C-5613 New Book Says Tobacco 'scare' Not Justified Tobacco and Health Volume 1 Number 1 [""Science Looks at Smoking"]
- CTRMN005610D-5613 Editors View Smoking-Cancer Tie As Unproved, Open Question Excerpts From Editorials Tobacco and Health Volume 1 Number 1 [Excessive Smoking Probably the Main Cause of Lung Cancer, While Moderate Smoking As Causation of Lung Cancer Has No Scientific Support]
- CTRMN005610E-5613 British Scientist Opposes Campaign Against Smoking Tobacco and Health Volume 1 Number 1 [Sir Ronald Fisher, British Statistician, Refuses to Produce Anti-Smoking Writing, States It As A Cause for Anxiety]
- CTRMN005610F-5613 'pick Your Expert, Take Your Choice' Tobacco and Health Volume 1 Number 1 [Witnesses Linking Cigarettes to Lung Cancer Testify Before House Operations Sub-Committee]
- CTRMN005610G-5613 'still Open Question' Tobacco and Health Volume 1 Number 1 [Authorities on Cancer State That Smoking Is Not Proven to Cause Lung Cancer]
- CTRMN005610H-5613 Smoking and Death Rates Tobacco and Health Volume 1 Number 1 [If Everyone Stopped Smoking There Would Be No Significant Change in Death Rate]
- CTRMN005614-5616 Summary of Comments for Delivery Before: Central Subsection, North Jersey Section, American Chemical Society, Elizabeth, New Jersey [Review of the Chemical Analysis of Cigarette Smoke and Investigations of Smoking and Lung Cancer]
- CTRMN005617-5620 the Public and Smoking Fear or Calm Deliberation? [How Doubt, Suspicion and Fear May Affect the Deliberation of Whether Cigarette Smoking Causes Lung Cancer or Other Ailments]
- CTRMN005621A-5624 TIRC Reports Progress in Smoking-Health Research Tobacco and Health Volume 1 Number 2 [Too Many Unknowns Exist Concerning Lung Cancer to Warrant Conclusions Citing Smoking As Causation of Lung Cancer]
- CTRMN005621B-5624 'tar' Misnomer for Condensed Smoke Tobacco and Health Volume 1 Number 2 [Difficulties in Analyzing Tobacco Smoke Make Tobacco Tar A Misnomer]
- CTRMN005621C-5624 New Statistics Contradict Anticigarette Theory Tobacco and Health Volume 1 Number 2 [Cigarette Smoking May Be Compatible with Normal Health Report on Done Smokers Who Have Longer That Average Life Span]
- CTRMN005621D-5624 TIRC Funds for Smoking Research Now Over $2,000,000 Tobacco and Health Volume 1 Number 2 [Scientific Advisory Board Approves 52 Grants and Renewals in 1957 Totalling $550,000]
- CTRMN005621E-5624 Press Questions Anti-Smoking Plan Tobacco and Health Volume 1 Number 2 [State-Supported Campaign Against Cigarettes Warranted in New York]
- CTRMN005621F-5624 Study Suggests Bronchitis May Be Prime Factor in Lung Cancer Tobacco and Health Volume 1 Number 2 [Preliminary Study at Beatty Institute Favors Bronchitis As A Factor of Lung Cancer]
- CTRMN005621G-5624 Doctors' Comments on Smoking-Health Tobacco and Health Volume 1 Number 2 [Increasing Number of New Chemicals in the Atmosphere at Fault for Rise in Cancer]
- CTRMN005621H-5624 Nation-Wide Lung Tissue Study Now Being Evaluated Tobacco and Health Volume 1 Number 2 [TIRC Studying Lung Tissues From 1,600 Persons]
- CTRMN005625-5648 Biological Aspects of Cancer Research Journal of the National Cancer Institute Vol. 30, No. 3 [St Background Research and New Information on Cancer Studies]
- CTRMN005649-5654 Interview the Cigaret Smoker and Lung Cancer Reprinted From Modern Medicine, Vol 26 [St Advises on Smoking and Its Relation to Health]
- CTRMN005655-5660 Comments on the Mortality of Smokers and Non-Smokers. A Paper by Harold W. Dorn Before the American Statistical Association Dec. 27, 1958 [Reflections on Figures Presented in Dorn's Paper]
- CTRMN005661-5671 An Experimentalist Looks at Statistics on Smoking [Reflections on the Figures in Dorn's Paper]
- CTRMN005672-5672 Letters to the Times Findings on Smoking [Statistical Proof of Link Between Smoking and Cancer Denied]
- CTRMN005673-5683 A Brief Review of the Smoking-Lung Cancer Theory [Review of Data Known on the Relation Between Cigarette Smoking and Lung Cancer]
- CTRMN005684-5686 Cancer-the Research Approach [Discussion on Cancer and A Category of Factors Which May Play Roles in Cause and Development of Cancer]
- CTRMN005687-5692 [Address Before the Burley and Dark Leaf Tobacco Export Association, Inc. Information About the Research Program Supported by the TIRC]
- CTRMN005693-5697 Some Phases of the Problem of Smoking and Lung Cancer the New England Journal of Medicine Vol. 264 No. 24 [St Disputes Findings That Smoking Causes Lung Cancer]
- CTRMN005698-5704 Some Aspects of the Lung Cancer Problem Reprinted From Punjab Medical Journal Vol. Xi No. 7 [St Discussion of Relationship of Cigarette Smoking to Lung Cancer]
- CTRMN005705-5735 Current Knowledge of Tobacco and Health [Discussion of Experimental Attack on Lung Cancer and Tobacco Use]
- CTRMN005736-5739 Cigarettes-Why More Research? Reprinted From the Yale Scientific Magazine [St Comments on the Uncertainties of the Correlations Between Cigarette Smoking and Lung Cancer]
- CTRMN005740-5740 Why Do People Think That Quitting Smoking Affects Their Appetite or Their Weight? the Apothecary [St Comments on the Scientific Basis of How Smoking Affects Hunger]
- CTRMN005741-5754 Address to Be Delivered by Dr. Clarence Cook Little, Scientific Director, the Council for Tobacco Research - U.S.A. At A Dinner Honoring the Centennial of the University of Kentucky and the Burley Tobacco Industry Lexington, Kentucky January 12, 1965 [Talk Addressing Research Programs of the University of Kentucky]
- CTRMN005755-5772 Communications and the Biological Sciences [Brief Discussion of Principles That Should Inspire and Guide Communications in the Biological Sciences]
- CTRMN005773-5785 Perspectives in the Experimental Approach to the Human Lung Cancer Problem [Experimental Research on Lung Tumors in Animals May Lead to Insights on Human Lung Cancer]
- CTRMN005786-5798 Tobacco and Health Research [Elaboration on the Purpose, Research Practices and Studies of the TIRC]
- CTRMN005799-5805 Tobacco and Health Research [Discussion of Experimental Studies by the TIRC Concerning Smoking and Health]
- CTRMN005806-5813 the Research Perspective on Smoking and Health [Discussion on the Search for Causes of Diseases with Which Smoking Has Been Associated]
- CTRMN005814-5820 Tobacco and Health Research [Discussion of Studies on Cigarettes and the Diseases Statistically Associated with Smoking]
- CTRMN005821-5834 Tobacco and Health Research - Where Shall We Go From Here? [Suggestions for Continuing Studies and Research on Cigarette Smoking and Health]
- CTRMN005835-5852 A Look Ahead Smoking and Health - Where Do We Stand? [Talk on Chronic Diseases and Factors of Their Causation and Development in Relation to Cigarette Smoking]
- CTRMN005853-5854 Smoking-Disease Links Continue to Lack Scientific Proof [Discusses the Role of the Council for Tobacco Research]
- CTRMN005854-5854 Lawrence Promoted to Vp Post at Mmi [Jack Riddle Announces the New Vp of Micro-Magnetic Industries]
- CTRMN005854A-5854 Philip Morris Expands Promotional Allowances [Discusses Special Offers Made to Philip Morris Vendors]
- CTRMN005855-5882 Chapter 3 the Tobacco Health Issue: An Overview of Medical Research [St Questions Methodology of Experiments Where the Sole Objective Was the Attempt to Induce Tumors]
- CTRMN005883-5900 the Research Program (Cancer Segment) of the Council for Tobacco Research - U.S.A., Inc. Presentation Before the Tobacco Working Group [Describes the Concept, Plan, and Purpose of the Council for Tobacco Research]
- CTRMN005901-5902 Smoking Prevention Education Act Hearings Before the Subcommittee on Health and the Environment of the Committee on Energy and Commerce House of Representatives Ninety-Eighth Congress First Session on H.R. 1824 [Statement of Sheldon C. Sommers]
- CTRMN005903-5919 [Regarding Anti-Smoking Bill]
- CTRMN005920-5931 Hearings Before the Subcommittee on Health and the Environment of the Committee on Energy and Commerce House of Representatives Ninety-Eighth Congress First Session on H.R. 1824 March 9 and 17, 1983 Serial No. 98-8 Statement of Robert Casad Hockett Regarding H.R. 1824 [Disputes Findings Set Forth in H.R. 1824 Regarding Cancer, Cardiovascular Disease, Atherosclerosis and Emphysema]
- CTRMN005932-5932 Hearings Before the Committee on Labor and Human Resources United States Senate Ninety-Eighth Congress First Session on S. 772 May 5 and 12, 1983 [Concerning Smoking Prevention Health and Education Act of 1983]
- CTRMN005933-5940 Statement of Sheldon C. Sommers, M.D., Consultant in Pathology, Lenox Hill Hospital, New York, N.Y. [Comments on Smoking Prevention Health and Education Act]
- CTRMN005941-5963 Hearings Before the Committee on Labor and Human Resources United States Senate Ninety-Eighth Congress First Session on S. 772 to Promote Public Health by Improving Public Awareness of the Health Consequences of Smoking and to Increase the Effectiveness of Federal Health Officials in Investigating and Communicating to the Public Necessary Health Information, and for Other Purposes Statement of Robert Casad Hockett Regarding S. 772 [Disputes Methodology of Experiments Which Expose Animals to Smoke]
- CTRMN005964-6009 Hearings Before the Subcommittee on Health and the Environment of the Committee on Energy and Commerce House of Representatives Ninety-Seventh Congress Second Session on H.R. 5653 and H.R. 4957 March 5, 11, and 12, 1982 Serial No. 97-106 [Disputes Methodology of Experiments to Demonstrate That Cigarette Smoking Can Cause Lung Cancer in Animals]
- CTRMN006010-6012 Testimony of Dr. Robert C. Hockett During Hearing on Cigarette Smoking and Health Before the Subcommittee on Oversight and Investigations of the House Committee on Interstate and Foreign Commerce, October 5, 1978 [Responds to Question Regarding Research on Health and Smoking]
- CTRMN006013-6023 Statement of Robert C. Hockett, Ph.D. Before the Subcommittee on Oversight and Investigation of the Committee on Interstate and Foreign Commerce in Response to the Letter Dated September 27, 1978 From the Chairman of the Subcommittee to William U. Gardner, Ph.D., Scientific Director, the Council for Tobacco Research - U.S.A., Inc [Discusses the Purpose of the Council for Tobacco Research]
- CTRMN006024-6069 Hearings Before the Subcommittee on Health of the Committee on Labor and Public Welfare United States Senate Ninety-Fourth Congress Second Session on S. 2902 February 19, March 24, and May 27, 1976 [Disputes Scientific Basis of S. 2902]
- CTRMN006070-6125 Hearings Before the Consumer Subcommittee of the Committee on Commerce United State Senate Ninety-Second Congress Second Session on S. 1454 Serial No. 92-82 [Discussion of Cigarette-Smoking and Peptic Ulcers]
- CTRMN006126-6135 Report of the Scientific Director [St]
- CTRMN006136-6189 Hearings Before the Consumer Subcommittee of the Committee on Commerce United States Senate Ninety-Second Congress Second Session on S. 1454 February 1, 5, and 10, 1972 [Discusses Edimeological Comparisons Between Smokers and Non-Smokers]
- CTRMN006190-6200 [Bibliography Listing Over 1,275 Articles and Books About Tobacco and Disease]
- CTRMN006201-6311 [Articles About Tobacco and Disease]
- CTRMN006312-6321 Hearings Before the Consumer Subcommittee of the Committee on Commerce United States Senate Ninety-Second Congress Second Session on S. 1454 to Amend the Federal Cigarette Labeling and Advertising Act to Require the Federal Trade Commission to Establish Acceptable Levels of Tar and Nicotine Content of Cigarettes [Statement of Dr. Sheldon C. Sommers]
- CTRMN006322-6348 Hearings Before the Consumer Subcommittee of the Committee on Commerce United States Senate Ninety-Second Congress Second Session on S. 1454 to Amend the Federal Cigarette Labeling and Advertising Act to Require the Federal Trade Commission to Establish Acceptable Levels of Tar and Nicotine Content of Cigarettes [Statement of Dr. Robert Casad Hockett]
- CTRMN006349-6359 Hearings Before the Consumer Committee of the Committee on Commerce United States Senate Ninety-Second Congress Second Session on S. 1454 to Amend the Federal Cigarette Labeling and Advertising Act to Require the Federal Trade Commission to Establish Acceptable Levels of Tar and Nicotine Content of Cigarettes [Statements of Dr. Sheldon C. Sommers and Dr. Robert C. Hockett]
- CTRMN006360-6370 Hearings Before the Consumer Subcommittee of the Committee on Commerce United States Senate Ninety-Second Congress Second Session on S. 1454 to Amend the Federal Cigarette Labeling and Advertising Act to Require the Federal Trade Commission to Establish Acceptable Levels of Tar and Nicotine Content of Cigarettes [References Reporting on Tobacco and Nicotine]
- CTRMN006371-6412 Hearings Before the Committee on Interstate and Foreign Commerce House of Representatives Ninety-First Congress First Session on H.R. 643 A Bill to Amend the Federal Cigarette Labeling and Advertising Act with Respect to the Labeling of Packages of Cigarettes and for Other Purposes (and Similar Bills) [Statement of Dr. Sheldon C. Sommers]
- CTRMN006413-6492 Hearings Before the Committee on Commerce United States Senate Eighty-Ninth Congress First Session on S. 559 and S. 547 Bills to Regulate Labeling of Cigarettes and for Other Purposes [Statement of Dr. Clarence C. Little]
- CTRMN006493-6533 Hearings Before the Committee on Interstate and Foreign Commerce House of Representatives Eighty-Ninth Congress First Session on H.R. 2248 A Bill to Amend the Federal Food, Drug, and Cosmetic Act So to Make That Act Applicable to Smoking Products [Statement of the Council for Tobacco Research U.S.A. History and Organization]
- CTRMN006534-6540 Hearings Before the Committee on Interstate and Foreign Commerce House of Representatives Eighty-Ninth Congress First Session on H.R. 2248 A Bill to Amend the Federal Food, Drug and Cosmetic Act So As to Make That Act Applicable to Smoking Products [Statement of Clarence Cook Little, SC.D.]
- CTRMN006541-6548 Hearings Before the Committee on Interstate and Foreign Commerce House of Representatives Eighty-Ninth Congress First Session on H.R. 2248 A Bill to Amend the Federal Food, Drug, and Cosmetic Act So As to Make That Act Applicable to Smoking Products [Statement of Robert Casad Hockett, Ph.D.]
- CTRMN006549-6577 False and Misleading Advertising (Filter-Tip Cigarettes) Hearings Before A Subcommittee of the Committee on Government Operations House of Representatives Eighty-Fifth Congress First Session [Statement of Dr. Clarence Cook Little]
- CTRMN006578-6611 False and Misleading Advertising (Filter-Tip Cigarettes) Hearings Before A Subcommittee of the Committee on Government Operations House of Representatives Eighty-Fifth Congress First Session [Statement Concerning the Origin and Purpose of the Tobacco Industry Research Committee and Its Proposed Functions]
- CTRMN006612-6614 False and Misleading Advertising (Filter-Tip Cigarettes) Hearings Before A Subcommittee of the Committee on Government Operations House of Representatives Eighty-Fifth Congress First Session [Hartnett Cites Scientists Doubting Smoking-Cancer Theory]
- CTRMN006615-6618 Research Into Smoking and Health [Arguments Against Tobacco Cancer Link]
- CTRMN006619-6623 [Study to Examine Reported Causes of Death in Each of 17 Regions in Houston Specifically the Five Major Respiratory Diseases]
- CTRMN006624-6624 A Frank Statement to Cigarette Smokers [Industry Promotes Research Into Tobacco Disease Link]
- CTRMN006625-6625 the Council for Tobacco Research - U.S.A., Inc. Board of Directors [Members of the Board]
- CTRMN006626-6627 the Council for Tobacco Research - U.S.A., Inc. Scientific Advisory Board [Members of the Board]
- CTRMN006628-6634 No. E-121,486 I. D. Rogers, Individually and As Independent Executor of the Estate of Marjorie Helen Rogers, Deceased; Et Al Vs. R. J. Reynolds Tobacco Company, Et Al in the District Court of Jefferson County, Texas 172nd Judicial District Third Amended Notice of Intention to Take Oral Deposition [Matters on Which Ctr Witnesses Must Be Knowledgeable]
- CTRMN006635-6967 Deposition of Dr. James Glenn [Deposition of Glenn in the Matter of Broin]
- Author
- Yeaman, A., Ctr
- Request
- 118
- Type
- ANNUAL REPORT
- Box
- 002
- UCSF Legacy ID
- knq30a00
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I
1978 REPORT
of
THE COUNCIL FOR TOBACCO RESEARCFi-U.S.A., Inc.
T7TE COUNCIL FOR TOBACCO RESEARCH-U.S.A., Inc.
110 East 59th Street, New York, N.Y. 10022
,. -. .
~'I'. Couocl( a.varda r..earc5Wanta tfl Icdcpiodea¢ sciaatim who an aa- ;,
m+W oogapiota tKitatisc ftoodom la sooduciinj tL.tr studia.. Oraatoes aSooo
ss:po~s[Dio tor or puLiishins their flndinyt ia the accoptcd acien-
;wrtaK-- tbroom dical and sclcuti8c journala and aododea.
4r;ThtcuA D+Ocmbar 1973, TThe Council appro.rod research projocta Lor 379
hlVaril$.tipts ia 247 mtadicai achoola, hospitals and reacarcb iasututloos. Thae
4, toi,iw wns ~tt ss1,9oo.ooa
This Itsr~ocil~t liaes o! curreat amd pcotioua r seanch pr~ sup-
-wrvA bby Tha Cuvr-D Ai.o lrcludt,d arn abstracts of 114 research papcr..
atrYs,vwiad-!iar Council w-ioott that wnsr oublisbed in acicntiBc iouraals dur-
;,4~Ls 1974. Pro}oct rndpicub ha.r so jar PubitahcQ 1,621 such papers.
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SCIENTIFIC ADVISORY I3OARD HANS ME1ER, D.V.M., Dr. Mcd. Vct., M.R.S.H. .--1
Senior StaQ Scientist ~
to The Council for Tobacco Rescarch-U.S.A., Inc. Thc Jackson Laboratory ~
as of Dcccmbcr 31, 1978
SHELDON C. SOMMERS, M.D., Chairman
Director of Laboratories, Lenox Hi11 Fioapital
Clinical Professor o/ Pathology
College of Physicians & Surgcons of Columbia University Bar Harbor, Maine
LEE W. WATTENBLRG, M.D.
Professor of Pathology
Department of Laboratory Mcdicine and Pathology
University of Minnesota Medical School
Minneapolis, Minncsota
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New York, New York ~.lz.
M.D. .
JOHN P. WYATT
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RICI-IARD J. BING, M.D. ,
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Director
and Intramural Medicine
Director of Cardiolo ~
Tobacco and Health Research Institute S..J
gy
Huntington Mcmorial Hospital, Pasadena, California
Professor of Medicine
University of Southern California School of Mcdicinc
Los Angeles, California University of Kentucky U
Lexington, Kentucky
JOSEPH D. FELDMAN, M.D.
Head, Dcpartment of Immunopathology
Scripps Clinic and Research Foundation
La Jolla, California
WILLIAM U. GARDNER, Ptt.D.
Scientific Director, The Council (or Tobacco Rcscarch-U.S.A., Inc.
E. X. Hunt Professor of Anatomy (emeritus)
Yale Univcrsity School of Medicinc
New Haven, Connecticut
ROBERT J. HUEBNER, M.D.
Chief, Laboratory of RNA Tumor Viruses
National Caoccr Inatitutc
Bcthcada, Maryland
Scientific Staff of T1e Council
WILLIAM U. GARDNER, Ptr.D.
Scientific Director
ROBERT C. I IOCKETT, Ptt.D.
Research Director
DONALD II. FORD, Ptt.D. VINCENT F. LISANTI, D.M.D.
Associate Research Director Associate Research Director
DAVID STONE, PN.D.
Associate Research Director
LEON O. JAt,OBSON, M.D.
Joseph Regenstein Professor of Biological Sciences
University of Chitago
CAicago, Illinois
HENRY T. LYNCN, M.D.
Professor and Chairman
Department o[ Preventive Medicine and Public Hcalth
Creighton University School of Mcdicine
Omaha, Ncbraska
CONTENTS
Introduction . . , . . . . . . . . 5
Abstracts of Reports . . . . . . . . . . . . 7
Canccr-Rclatcd Studics , . . . . . . - . . 7
Thc Respiratory System . . . . . . . . . . . . 26
Hcart and Circulation . . . . . . . . . . . . 41
Ncuropharmacology and Physiology . . . . . . . . . 49
Pharmacology and Biochcmistry . . . . . . . . . . 62
Immunology and Adaptive Mechanisms . . . . . . . 70
Epidemiology . . . . . . . . . . . . . . . . 77
Active Projects . . . . . . . . . . . . . . . . . . 83
Complcted Projccta . . . . . . . . . . . . . . . . 92
Index of Principal Investigators . . . . . . . . . . . . 103
Index of Scnior Authors . . . . . . . . . . . . . . . 104
Introduction
This report marks the completion of 25 years in which The Council for
Tobacco Research has supported a program that has becorne the .rorld's most
extcnsive non-govcrnmental rescarch cffort rekvant to smokinj aod health.
When The Council was establiahed in 1954, it adopted a basic policy that
has been followed without deviation: to place responsibility for research policy
and programming in the hands of a Scientifk Advisory Board and to have the
research conducted by independent investigators in their own institutions with
no strings attachcd.
Up to the cnd of 1978, the program has resultod in the publication of
1,622 «ports and articles that acknowkdged Council support. Thus, the pro-
gram has produccd considcrablc data relatcd to smoking and health during a
period that also saw the generation of considerabk controversy and emotion
about the subject.
No one can fully predict at this time what theae publications will mean
in the scarch for the answcn to the problem of the major, aging-associated
and constitutional discasa of cancer, heart discase and chronic pulmonary
ailmcnts. Howcver, the hope is that some day the Bndinga from one or more
studies may provide keys or links for a major biomedical advance.
Thc Council cxists today because the compkx etiology of these constitu-
tional diseases remains unraveled. Theae diseases have been associated statis-
tically with smoking, but such associations are not proof of cause and eRcct.
The diseases are extremely complcx-cancer itsel(, for exampk, is not one
disease but many-and finding their causes will not be easy.
The overall importance of genetic factors is being increasingly reeognixed,
acccptcd and studicd. Progress is being made, but it is nocessari.y slow and
painstakinQ.
The statement of many years ago that we live in a "sea of urcinogens"
is supported by much recent and current research. Many thinp-both natural
and man-madc-that we eat, drink and brcatlx have been implicated in cancer
and heart discasc, at least in laboratory experiments. But exact proof, proof
that mccts scicntific criteria, is often lacking.
Whatever contribution to scientific knowledge that may be attributed to
The Council's program, as evidenced In part by the numerous reports in the
literature, is due principalty to the members of the Scientific Advisory Board,
past and present. These scientists, who have always maintained their irutitu-
tional atfiliations, have given unsclSahly of their time and talents. The result
of their combined ctTort (or so many years is an imaginative undertaking that
has enabled many researchers to pursue idcas aod theories lhat might otlur-
wise have gone unexplored for lack of support.
7Tie Council is gratified at the response through the years of the scicn-
tists who have applied to it for research support. This interest remained high
in 1978 and the number of requests (or support of new and continuing ro-
search assures a worthy future.
This report contains abstracts of research Andinp published in 1978 that
acknowlcd^cd Council sponsorship. As can be sern, the major emphasia eoo-
tinucs to be directed toward canar, the cardiovascular system and the respira-
S
1
1
tory tract. The abstracts of the published papers arc indicative of the areas of
research supportcd by The Council.
The Council looks back with satisfaction at what has been accomplished
in the last quaricr{cntury. It looks to the futu;c with optimism and hope for
research that will hclp solvc the mysteries of canccr, heart discasc and chronic
pulmonary ailments. The Council pledges to continuc its support of indc-
pcndcnt invcatigaton in their efforta to add to scicnti(ic knowledge rclated to
smoking and health.
Abstracts of Reports
Following arc abstracu, approved by the authors, of reports on' new
research acknowledging support from The Council that have appeared in acicss-
tific journals since publication of the 1977 Report. The name of the «cipicat
is in italics.
The abstracts arc grouped under these headings: I. Canccr-Rclated Studies,
II. The Respiratory System, Ill. Heart and Circulation, IV. Ncuropharmacolojy
and Physiology. V. Pharmacology and Biochcmistry, VI. Immunology aad
Adaptive Mcchanisms, VII. Epidemiology.
I. Cancer-IRelated Studies
CRITERIA FOR SELECTING CHEMICAL COMPOUNDS FOR
CARCINOGENICITY TESTING: AN ESSAY
Thc ever increasing number of organic compounds constantly being intro-
duced into the various scgmcnta of thc worldwide economy creatcs the need
to devise a tormal schenx of selection criteria (or testing o( suspected car-
cinogcns, and to establish priorities (or such testing. Four categories of criteria
must be considered: (I) structural, (2) operational, (3) "guilt by associa-
tion," and (4) "after the fact." This essay gives an analytic discussion of each
of these criteria. Structural criteria arc deduced from a general perspective of
the structurc-activity relationships of known carcinogens. The operational cri-
tcria, which are complcmentary to the strudural ones, represent the sum of
the bio-functional capabilities of chemical compounds. These capabilities cor-
rclato with thc ability to induce malignancy through such mechanisma as, for
example, mutagcnicity, induction of DNA rcpair, and immunowppresaion. The
"guilt by association" criterion uates that a compound belonging to a ehem-
ical class already known to contain several other compounds atablished as
potent and multitargct carcitagcos should be tcsted under more stringent coo-
ditions than those of the standard bioassay. 7Le 'after the (act° criterion
dcAncs previous epidcmiologic indiutiooa as the basis for ackctinj certain
chemical agents for carcinogenicity testing. Tht overall sigrtillcance of the
bioassay data obtained on individual compounds, however, should be oat-
sidcrcd in conjunction with other endoj+enous and esoQetsous intcrauinj faa
tors such as: (1) synergistic and antagonistic activity betwocn multiple car-
cinogenic agents; (2) eftects of twncancinojenie environmental agents on
carcinogenic activity; and (3) virsuts, nutritioo, radiation, age, stress, endo-
crine balance and the state of the immune sutroeillanee system. The huge
number of agents and (acton, their interactiorss and the eoexistenoe of fro-
quently conAicting societal goala, indicate the need for the esublclunuu o(
vcnatilc scientificolcgal standsrds and juidolioes applicable to catcgories and
types of chemical agents rather than to ladividual eomp9unds.
Arcos, J. C.
Journal of Environmenial Pathofopy and Torkolory I433-45E, 1978.
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Otlrer support: National Cancer Institutc.
From the Seamen's Memorial Research Laboratory. U. S. Public Hcalth Scrvice
Hospital. New Orkans; and the Department of Mcdicinc, Tulanc Mcdical
Center, New Orleans.
ULTRASIRUCTURAL AND METABOLIC DETERMINANTS OF
RESISTANCE TO AZO-DYE AND SUSCEPTIBILITY TO
NITROSAMINE CARCINOGENESIS OF THE GUINEA-PIG
The azo dye rcductase and nitrosaminc dcalkylasc activities of normal
guinea-pigs and rats werc compared to those of animals fed azo dye and
nitrusamine. Electron microscopy revealed ultrastructural alterations of lhe
guinca pig liver during nitroaamine administration. Diethylnitrosamine (DEN)-
induced hepatic tumor cells showed extensive proliferation of thc rough ersio-
plasmic rcticulum (ER), while the smooth ER was quite sparsc; the oppositc
was true in the premalignant liver. In the rat, howcvcr, administration of
either DEN or 3'-methyl-4-dimethylaminoazobcnune (3'-Me-DAB) caused
prolifcration of the smooth ER and sparsity of the rough ER in both prc-
malignant and malignant tissue. In both specics, the number of ribosomca on
the outcr surface of the liver rough ER was greatly reduced as was the RNA/
protein ratio, which correlated with a dccreased response to an SH probe
in microaomal suspensions. Azo dye rcductaae activity was higher in untrcatcd
rats than in untreated guinea-pigs. After six weeks of 3'-Mc-DAB fceding,
howcvcr, this was 76% lower in the rat while there was no significant decrcase
in the guinca pig, which is rcfractory to azo dye carcinogenesis. Thus, as in-
testion approached the tumoriycnie threshold dose, the rat liver i ability to
inactivate the dye was much impaired, but not that of the guinea pig. Control
kvcls of nitrosamine dcalkylase were identical in both species, howcvcr. and
remained essentially unchanged after 10 weeks of DEN administration. Since
nitrosamine dcalkylation represents activating metabolism, this provides the
basis for the identical suaceptibilitics of the rat and the guinea pig to DEN
carcinogcnesis. Of the two enzymes examined, only the guinea pig azo dye
rcductase appears to be independent of glucose r,cpression, sincc its activity
was unchanged by starvation. St.rvation-induocd ckvation of azo dye rcductasc
activity in the rat was not affected by 3'-Mo-DAB administration and only
slightly influenced hy DEN. In both spocies, however, DEN abolished the
uarvation-induced increasc of nitrosamine dcalkylation, while 3'-Mc-DAB
docreased it only slightly.
Bryant. G. M.. Sohal, R. S., Argus, M. F., and Arcos, J. C.
British Journal o/ Cancer 36:678-691, 1977.
OtJrer support: National Cancer Institute.
From the Department of Mcdicine, Tulano Medical Center and Seamen's
Memorial Rcscarch Laburatory, U. S. Public Health Service Hospital, New
Or)cans; and the Department of Biology, Southern Methodist University,
Dallas.
i
IIYDROCARBONkNITROSAMINE PULMONARY SYNCARCINO-
GENESIS: RECIPROCAL EFFECTS ON METABOLISM
This study rctwrts on the enxymological correlates of the pulmonary syo-
carcinogenesis which has been observed between methylcholanlhrene (MC)
and dirncthy/nitrosamine (DMN) following acute administration of the tar-
cinogcns. Ex pcrimcnt ally, aryl hydrocarbon hydroxylase (AFfll), epoxido
hydrasc, DMN-dcmcthylasc, and glutathione-S-epoxide transferase activities
were studied in the liver and lung of DBA/2J and C57BLJ61 mice, two strains
which arc, respcctively, noninducibk and inducible for hepatic A}IH. Chan=e
in thcsc enzyme activities was determined following acute administration of
MC, DMN, and their combinations. In the livcr-except for a substantial in-
duction of hcpatic Alill in the CS7BL/61 strain-thc metabolic pattern is
vcry similar in the two strains. In both strains DMN-0cmcthylase is highly
sensitive to DMN pretreatment at the six mg/kj level. Increase of DMN to
the total syncarcinogcnic dox of 60 m=/k= abolishes induced AHH in the
C57BL/6J and brings about substantial inhibition of all other enzymes studied.
In the lung of the two strains, induced AHH was found to be highly acnsitive
to DMN pretreatment in the DBA/2J, and DMN-demethylase II (the only
DMN-dcmethylax present in the lung) was substantially reduced following
pretreatment with 60 mg but not with 6 mg DMN. The most interesting ro-
sults in the lung arc seen with the CS7BU61 strain since, with 60 mg DMN/
kg, there is a substantial decrcase of the epoxide hydrase together with a
substantial increase of the AHH. This suggats a mechanistic intcrpretation
of lhe AIIH increase within the framework of the known pathways of hydro-
carbon metabolism and a greater susceptibility of the C57BIJ6J strain to the
combined administration of MC and DMN.
Arcoi, J. C. cr al.
In: Gclboin, H. V. and Ti o, P. O. P. (cds.): Polycyclic Hydrocarbotir awd
Canccr-Environmcnt, Chcm/rtry and Merabolirm. New York: Aeademie
Press, 1978, vol. 1, pp. 271-282.
From Tulane University School of Medicine, New Orleans.
DIFFERENTIAL EFFECTS OF.&NAPTHOFLAVONE AND
PREGNENOLONE-16o-CARBONfi'RILE ON DIMETHYLNITRO-
SAMINE-INDUCED lIEPATOCARCINOGENESIS
The carcinogcnicity of dimcthylnitroaamine (DMN) u inhibited by the
co-administration of either 3-nxthykboianthrcne or aminoaeetonitrik, eoro-
pounds which substantially lower the activity of DMN-0cmethylase, a micro-
somal mixed-function oxidaac that catalyzes the auivation of DMN. In the
prescnt investigation aimed at elucidating further this corrclation, the died
of administering p-naphthoAavone (i9-NF) and poegneaoionrl6.urbonitrib
(PCN) on the hcpatocarcinogtnicity of DMN ia malo SD rats waa axpiorcd.
.Both r4-NF and PCN arc potent ncpresson of the low-Michaeliscon.tant eo-
zymatic form of DMN-demethylase. Hepatic tumors were found in every
group of rats rccciving DMN alone or in combination with A-NF or PCN.
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The morphology of thcse tumors was quite similar for all three groupa, with
53% of the 53 liver tumors observed being angiosarcomas. DMN-induced
hcpatocarcinogencsia was partially inhibited by PCN and enhanced by O-NF.
Scvcn livcr tumors were found in 45 rats fcd DMN plus PCN comparcd to
32 liver tumors in 43 rats fcd DMN plus 6-NF; 14 liver tumors werc found
in 43 rats fcd DMN alone. No livcr tumors were dcacctcd in rats that rcccivcd
only PCN, A-NF, or the administration vehicln. The uncxpectcd enhanccnunt
of DMN-induced caccinogenesis by O-Nl' prompts a rcexanunation of tlic
presently accepted activation mechanism of DMN.
Argus, M. F.. Hoch-Lircti, C., Arcos. J. C., and Conncy, A. H.
Journal o/ nce National Cancer lnssiturc 61(2) :441-449, 1978.
Olher auppori: National Canccr Institute.
From the Scamcn i Memorial Research Laboratory, U. S. Public Hcalth Service
Hospital, and the Department of Mcdicinc, Tulanc University School of
Medicine, New Orlcans.
USE OF HIGH CONCENTRATIONS OF DIMETHYLNITROSAMINE IN
BACTERIAL LETHALI'IY, MUTAGENESIS, AND ENZYMOLOGICAL
STUDIES
Previous studia have established that the potency of dimcthylnitroumine
and dicthylnitrosamine in bringing about conformational changes in protein
is comparable to that of urea and guanidinium chloride, well-known protein-
denaturing agents. In addition, an optical rotatory dispersion study of the
ovalbumin conformational change as a function of dimethylnitroaamine con-
ocntration had indicated a cotscentrationdcpendent ambivalent effect on pro-
tein conformation. Thus, at concentrations of, and greater than, about 200
mM, dinxthylnitrosamino brings about dcnaturation. However, at conuntra-
tions from 200 mM downward the b, constant of ovalbumin increascs with the
dc.:rcase of dimethylnitroramine concentration, suggesting that, In this con-
ccntration range, dimcthylnitrosamine has a refokling ("tif,htening") rather than
unfolding (denaturing) effect on the protein secondary structure. Because of
its proteinrknaturing ability, dimethylnitroaaminc at high concentrations can
bring about cell death. !n eontraat, when 20 to 200 mM dimcthyloitros.minc
is used iss enzyme aad mutagenesis aasays, because of ita refolding cNect on
protein secondary struttuna at these concentrations, it may produce allosleric
enzyme coaformational changes in vfrro, thereby possibly creating artifactual
phcnomcna. Indeed, the use of nonpharmacologiully high concentrations of
dimethylnitroaamirsc and dkthylnltrosamine appears to be the basis of con-
Aicting rcporta on the trprcasibillty versus inducibility of dimcthylnitroaaminc
demethylase and dicthylnitroaamine doethylase and on the effect of ctuymc
Induccr pretreatment on nltrosamino mutagenicity activation by microsomcs.
Raxnt investigations wggat that the apparent conflict is due to the existence
of two enzymic forms of dimcthylnltrosamine demcthylase that respond in
diametrically opposite ways (namely, repression and induction) to enzyme
inducer ptttrutn-.cnL 7bcse obscrvations and others kad the authors to con-
cludc that the conrr.entratton of dimethylnttrosamino (or any other ndnosamtne)
used in in virro assays should be kept under 20 mM, and preferably bdow
S mM. Since the purpose of studying the metaboiism, mutagenicity, and eeUu-
lar cftccts of dimethylnitrosamine and other nitroumines is principally to gain
insight into the mcchanism of their carcinogenic effect, physiologically realistic
tcsting lcvcls should be observed.
Argus, M. F. aud trcos, 1. C.
Cancer Re.rearch 38:226-228, 1978.
a
L.J
.5~:..+
.1...
From the Seamen's Memorial Research Laboratory, U. S. Public Health Service Hospital, and the
Dcpartmcnt of Medicine, Tulane Medical Center, New rX_
Orlcans. ~: ~+++
TISSUE AND SUBCELLULAR DISTRIBUTION OF sH-DIOXANE IN
THE RAT AND APPARENT LACK OF MICROSOME-CATALYZED
COVALENT BINDING IN THE TARGET TISSUE
Dioxane, a commonly used industrial and laboratory solvent, has been
known to exhibit both toxic and carcinogenic activity. As part of a series of
investigations aimed at clucidating the mechanism of these cRecta, this paper
prescnts data on the distribution of sH-dioxane among a number of rat tia-
sucs and various subccllular fractions of rat liver.° At various times after
intraperitoneal injcction, diox.ne was distributed more or less uniformly
among various tissues (liver, kidney, spleen, lung, colon, and skelctal muscle),
which is consistent with its polar/nonpolar nature. However, in contrast to
this nearly uniform distribution. studies of the nature of binding revealed largs
tissue differences. The liver (the main target of urcinogcnesis), oolon (do-
accnding segmcnt), and spleen sho.ved a greater amount of "covaknt" binding
as mcasurcd by tbe incorporation of radioactivity into lipid-free, acid-ituolubie
materials. Much Icss "covalent" binding occurred In the skektal muscle and
blood. Invcstigations of the subccllular distribution in liver indicated that most
of the radioactivity was in the cytosol, followed by the microsomal, mito-
chondrial, and nuclcar fractans. The binding of dioxane to the maerornoir
cules in the cytosol was mainly noncovaknt. The percent covalent binding
was highest in the nuclcar fraction, followed by mitochoodrial and mietosortul
fractions and the whole homogenate. Pretreatment of rats with induun of
microsomal mixcd-function oxidases had no significant effect on the covalent
binding of dioxane to the various subcellular fractions of the liver. There is
no microsomc-catalyzed In vitro binding of dioxane to DNA under conditions
in which there is cxtcnsivs binding of benzo(aJpyrene.
Woo. Y-T., Argus, M. F. and Arcox, J. C.
Ll/e Sciences 21(10) :1447-1456, 1977.
Other support: National Cancer Institute.
,
From the Seamcn's Memorial Research Laboratory, U. S. Public Health Savice
Hospital, aod the Department of Medicine, Tulane University, New Orkans,
10 11
STRUCTURAL IDENTIFICATION OF p-DIOXANE-2-ONE AS TI1E
MAJOR URINARY METABOLITE OF p-DIOXANE
Intcnsive dioxanc expo.ur+c causes severe liver and kidncy damage and
even death. The compound is also a hepatic carcinogen in rats. In this invcs-
ti3ation of the in vivo mctabolism of dioxane, gas chromatography (GC) of
the volatile compounds present in the urine of rats administcrcd dioxane re-
vulcd a major metabolile. 7Te latter was dctcclable only at low pft levcl%,
and the amour.t excreted was buth dosc- and tinu-dcpcndcnt, rcaching a maxi-
mum 20 to 28 hours aftcr intrapcritoneal injection of dioxanc. Administration
of dicthylcoe glycol produced the same mc/atwlitc, but mostly within tlic firsl
16 hours, sugycstins that this compound may bc an intcrmcdiatc in the in
vivo metabolism of dioxanc. Under similar conditions, ethylcnc glycol, di-
glycolic acid and oxalic acid did not induce excretion of the mctabolite. The
isolated and purified metabolite displayed an intcnsc carbonyl band at 1,750
em-1 in thc infrared (1R) spectrum. Its nuclear magnetic resonance (NMR)
spectrum indicated two triplets and one singlet of equal intensity at 3.85, 4.48
and 4.37, reapeetively. Upon GC-mass spcctrophotometric studies, there was
a parent peak at m/e 102. The metabolite was identified as p-dioxanc-2-orx,
as confirmed by comparison to its synthetic reference compound, which ex-
hibited the aame IR, NMR, and GC-mau spectra as the unknown. A tenta-
tive metabolic pathway for dioxanc is presented; microsomal mixed function
oxidascs appear to be involved in this pathway. Preliminary experiments indi-
eate that tho metabolite is considerably more toxic than the parent compound.
Its poicntial health hazard remains to be assessed, especially since it is used
as a commercial and industrial preservative.
Woo, Y-T,.1rcos, J. C., Argus, M. F., Gritfin, G. W., and Nishiyahaa, K.
Naunyn-Schmledabrrg's Archives oJ Pathology 299:283-2g7, 1977.
Other support: National Cancer Inslitutc.
From the Scamen's Memorial Rcxarch Laboratory, U. S. Public Health Service
Hospital; the Department of Medicine, Tulane University; and the Department
of Chcmistry, University of New Orleans, New Orleans.
EFFECT OF MIXED-FUNCTION OXIDASE MODIFIERS ON
MLrI'ABOLISM AND TOXICITY OF THE ONCOGEN DIOXANE
The etTect of inducers and inhibitors of mixed-function oxidases (MFO's)
on the /n vivo metabolism of dioxane fn the rat was studied with both non-
radioactive and "C-labeled dioxane. In addition, the effocts of various inducers
on the acute toxicity of dioxane and its principal urinary motabolitc, p-dioxane-
2-onc, were examined in an attempt to elucidate the relationship bctwecn the
metabolism and tqxicity of this commonly used solvent. Results showed that
pretrealment of mak Sprague-Dawlcy rats with the inducen phenoharbital
(PB), polychlorinated biphcnyls (PCB), and, to a much leszer extcnt, 3-
mcthylcholanthrcnc (MC), increased the metabolite excretion and shortened
lhc time of onsct bf peak excretion of the metabolite. On the other hand, an
inhibitor or repressor of MFO's, such as either 2,4-dichloro-6-phenylphersoxy-
elhylamine or cobaltous chloride, decreased the metabolite excrction. Thae re-
suits sub%tantiate the involvement of MFO's in the in vivo metabolism of
dioxanc. Whcn the relationship between the metabolism and the acute toxicity
of dioxanc was explored, it waa scen that prlioxane-2-0nc was considerably
more toxic than dioxairo. '!bc acute toxicity studies showed an apparent
corrclation bctwccn the metabolism and toxicity of dioxane In PCB- or MC-
prctrcated rats. llowcvcr, I'll pretreatment had no eRcct on toxicity in spite
of autntantially incrcasing dioxanc's metabolism to p-dioxanc-2onc. Since this
lack of PB clfcct indicates that p-dioxanc-2-onc requires further metabolism
to exert its toxic effect, the totality of these results suggcsts that the generation
of (he toxic substance from dioxane may involve a multistep mcchanism with
p-dioxane-2-onc scrving as an intermediate.
Woo, Y-T., Argus, M. F. and ./rcor, J. C.
Cancer Research 38:1621-1625, 1978.
Other aupport:: National Cancer Institute.
From the Seamcn's Memorial Research Laboratory, U. S. Public Health Service
Hospital, and the Dcpartment of Medicine. Tulane University Medical Ccnter,
New Orleans.
RAI)fOACTIVE ASSAY FOR ARYL HYDROCARBON HYDROXYLASE.
IMPROVED METHOD AND BIOLOGICAL IMPORTANCE
This report describes an isotopic AHH assay, which measures all the
metabolitc.s formed during the !n vitro incubation of various tiausa (liver,
intcstine, lung, kidney) with (sH)-benzo(a)pyrene and accurately detetmines
lower enzymatic activitics such as those found in the lung or kidney. 'Ihe
addition of two volumes of a IM aqueous KOH/dimethylsulfoxide (15/85-
v/v) mixture to the enzymatic Incubation mcdium, makes it posaibie to selee-
tivcly extract the unmctabolizcd bcnzo(a)pyrenc In hexanc. Thus, Ihe radio-
activity remaining in the water phase represents ail the metabolites synthesized
In vitro. Whitc kss sensitive than the more commonly used fluoritnetric method,
this new technique, whose lower limit of sensitivity is estimated to be about
2.10-tt moles of lotal metabolita formed /ml incvbation medium, is ex-
trcmcly accuratc, can measure cxtrahepatirc and low AHH activity, and is not
particularly photosensitive.
Van Cantfort,l.. Dc Graevc, 7. and C(den, J. E.
Biochemical and Iliophyslcal Research Commwnieatfon.r 79(2) 505-512, 1977.
From thc Laboratoirc de Chimic MFdicak, Ins:itut dc Pathologie. Sart-Tilman
par Li2gc, Bcleium.
/
..f:..
Z.
12 13
COMPARISON OF ARYL HYDROCARBON HYDROXYLASE
INDUCTION IN CULTURED BLOOD LYMPHOCYTES AND
PULMONARY MACROPHAGES
In this study, In vitro inducibility of aryl hydrocarbon hydroxylasc (AHH)
in freshly lavaged pulmonary alveolar maerophagcs (PAM) was comparcd to thc
degree of induction of AHH in cultured lymphocytes from 15 smokers and 8
nonunokars with a variety of nonneoplastic lung discases. Valucs ohtiincd
for AHH in PAMs and in lymphocytes from patients within the nonsmokcr
and smoker groups were similar. Levcls of AHII in PAMs freshly obtained
by Iavagc were higher for smokers than for nonsmokers. With PAMs from
nonsmokers, levels of Atilt were virtually idcntical for cells cultured for
24 hra, with rw inducer in the mcdium and for cclls fresLly Iavrgcd hum lhc
lung. In contrast, valuca for PAMs from snrokcn wcrc rcduccd to atxsut halt
thc original kvcls aflcr culture for 24 hra. with no induccr in the mcdium.
Atilt values wcre similar when noninduced enzyme levels were comparcd for
nonsmoker or smoker PAMs and lymphocytes. Also, when PAMs and lympho-
cytea from srnoken or nonamokers wene cultured in the presence of BA,
similar cnzyme induciion was observed. Results from these studies indicate
that AHH kvela in one cell type can accurately reflect levels measured in thc
other cell type. However, dgsrcttc smoking affccta the noninduced as wcll as
the BA-irsduced kvcla of the eozyme. This is the flrst time that cells from two
separate tiuucs from individual subjects have been shown to possesa similar
AHH induction capabilities when tested under identical culture conditions.
By measuring AHH in two separate tissues from the same individual, problems
previously encountered in using a single tissue for analysis of an individual's
AHIi characteristics might be resolved. This added dimension for the analysis
of AHH in individuals might also provide researchers with another tool for
evaluating the relationship of AHH to chemical carcinogcncsis.
McLemorc, T. L., Martln, R. R., Toppell, K. L. Busbce, D. L., and Cantrcll,
E. T.
The Journal of Clinical InvesrigarJon 60:1017-1024, 1977.
Other aupport: National Institutes of Health.
From the Department of Medicine and the Department of Microbiology and
lmmunology, Baylor College of Medicine, Houston; and the Dcparlmcnt of
Biological Scicnccs, North Tcxas State University, Denton.
ANALYSIS OF ARYL HYDROCARBON HYDROXYLASE ACTIVITY
IN HUMAN LUNG TISSUE, PULMONARY MACROPHAGES
AND BLOOD LYMPHOCYTES
While variation in the degnea of aryl hydrocarbon hydroxylase (AHH)
inducibility has been observed in pulmonary alveolar macrophagcs (PAM)
and lymphocytes from diftercnt (ndividuals. AHH values in these cells have
not been related to the AHH activity in other autologous tissues. In this
uudy, the AIiH activity in fresh surgically excised lung tissue, fresh PAM
and periphcral bl.od lymphocytes from 14 cigarette smokers (7 with untreated
primary lung cancer and 7 noncancer patient.), was tneasurcd fluorometrically.
Individuals without cancer showed a good eorrelatioo (r = 0.975, p<.001)
between the PAM's AHH levels and the AHH inducibility (expressed as fold
induction) in their culturcd, mitogcn-stimulated lymphocytes. In the eaacor
patients, howcver, thcse values were dissociated. In addition, the fresh lung
tissue AHH levels and the cultured lymphocytes' fold-induetion ratios eorre,
latcd positivcly in noncancer patients but not in the cancer patients. There was
closc agreement between fresh lung tissue Atilt and fresh PAM from indi-
vidual canccr-frcc patients, but these valucs were only weakly correlated in
those with canccr. Upon simultancoru comparison of Atilt aclivity in fresh
1'AM and in lrc.h lung tissuc, and Atilt inducibility in cultured lymphocyta,
an cxccllcnt rclatiunship was found between these values in all three tissues
fur individual narscancer patients (r = 0.987, p<.001). However, these did
not correlate in individual lung cancer patients. According to the data, while
the capacity for Atilt induction in cancer-frce cigarette smokers is similar
in the tissues studied, lung cancer patients do not have positively correlated
AHH values in thcsc tissucs.
McLcmore, T. L., Marfln, R. R., Pickard, L R., Sprinaer, R. R., Wray, N. P.,
Toppcll, K. L, Mattox, K. L., Guinn, O. A., Cantrcll, E. T., and Buabee, D. L
Canccr4l(6):2292-2300, 1978.
Other support: National Institutes of Health, National Cancer Institute and
the American Cancer Society.
From the Departments of Medicine and Surgery, Baylor College of Modicino
and Vetcrans Administration Hospital, Houston; and the Department of
Biological Sciences, North Texas State University. Denton.
DISSOCIATION BETWEEN AR'k HYDROCARBON HYDROXYLASE
ACTIVITY IN CULTURED PULMONARY MACROPHAGES AND
BLOOD LYMPHOCYTES FROM LUNG CANCER PATIENTS
Lymphocytes and pulmonary alveolar macrophages (PAM) used for '
evaluation of aryl hydrocarbon hydroxylaso (AHH) induction were obtained
from IS noncanccr and 14 primary lung cancer patients. Enzyme levels were
measured in cells cultured with or without the induoer benzanthracene (BA).
Toe mean levels of Atilt showed no di8ercnoo between noncancer and eanoer
patients for either nonlnduced or BA-Induoed eella. Absolute levels and fold
induction of Atilt in PAM and lymphocytca from individual noncarsar
patients were positivcly eorrclated. However, oomp.riaoo of theae values in
PAM and lymphocytes from individual lung cancer patients demonstrated no
positive correlation. In further study, comparison of enzyme activity in macro-
phagca freshly lavaged from the lun= and BA-faduced activity in cultured
PAM revealed a positive correlation for both nottcancer and lung cancer p.-
tients. Similarly, comparison of enzyme activity in fr+esh macrophatcs and fold
induction valucs in cultured PAM was also well cocrelatod for both jrarpa oi
patients. From these studies, it would appear that meawicmertt of AHH in
more than one tissue obtained on the ume day frnm a given individual may
14 '
IS
distinguish diffcrences bctween noncancer and lung cancer paticnts. In non-
cancer patients. thcre is a good agreement between values for AHH in fresh
PAM and cultured lymphocytes; however. when similar mcasuremcnts arc
compared in individual lung cancer patients, the AHH values in ccllc from
the two different tissues are dissociatcd. Since this dissociation betwcen AHH
levels is consistently found in lung cancer patients. a comparison bctwccn Alilf
levels in cultured PAM and lymphocytes could be of diagnostic aid when lung
cancer is suspectcd.
McLemorc, T. L., Martin. R. R.. Wray, N. P., Cantrell. E. T., and Bushcc,
D. L.
Cancer Rercarch 38(11) :3805-381 I, 1978.
Other aupportr National Institutes of Health. American Cancer Society
and the Veterans Administration Hospital, Houston.
From the Departments of Medicine and Microbiology and Fmmunology, Bay-
lor College of Medicine, and Veterans Administration Hospital, Houslon; the
Department of Biological Scicncea and the Genetics Center, North Tcxas State
University, Denton, and the Dcpartmont of Pharmacology. Tcxas College of
Osteopathic Mcdicinc, Fort Worth.
EFFECTS OF SELENIUM ON.ARYL HYDROCARBON HYDROXYLASE
ACTIVITY IN CULTURED HUMAN LYMPHOCYTES
This paper examina the effects of selenium (Se) on induction of aryl
hydrocarbon hydroxylaae (AHH) activity in lymphocyte cultures and on the
onzyme activity itself. Experimentally, human lymphocytes were cultured both
in the preacnce and abatence of inducen of AHH. The presence of 10' M Sc
during the last 24 hra. of culture (cornaponding to the time when inducer was
present) or during the entire culture period had no inhibitory ctTect on AHH
activity in either tsonindutxd or induced cells. However, the presence of Sc
in the usay itself inhibited AHH activity by more than 50%. This level of
inhibition was seen at concentrations of the substrate benzo(aJpyrenc of 1, 3.
10, and 100 µm and Se concentrations of 0.1, 0.3, 1, and I0mM, respectively.
Interatingly enough, when AHH activity wu measured in noninduccd cells
in the presence of low concentrations of Se, the AF(H activity was slightly
higher than when Sc was abscnt. Thao findings indicate that the inhibitory
cfkct of Sc on tumorigencsis in studies with several experimental animal sys-
tems may be explained in part by the inhibition of microsomal oxidascs rc-
sponsibie for metabolic conversion of prccarcinogcns to ultimatc, electrophilic
carcinogens.
Rasco, df. A., Jacobs, M. M. and Griffin, A. C.
Cancer l.etterl 3:295-30 t, 1977.
Other aupport: National Cancer Institute.
From the Departments of Biology and Biochemistry. The University of Texas
System Cancer Center, M. D. Andcrson Hospital and Tumor Institute, Houston.
e
C
GALACTOSYL TRANSFERASE IN BENIGN AND NEOPLASTIC C
HUMAN B1.ADfJER MUCOSA
Uridinc 5'-diphosphale galactose:glycoprotcin galactosyl transfcrase (Gal-
X), an enzyme which is involved in the bioaynthesis of complex carbohydrates
of cell mcmbrancs, has been implicated in intereellular recognition, adhesion
and differentiation, and associated with somo human endodermally derived
tumon. In the present study of the activity of G.I-X in human transitional
ccll carcinoma, the homogcnatn of four established transitional cell carcinoma
lines (MGII-l, MG}l-2, RT-4; and T-24) were shown to have signi8cantly ~
increased Gal-X activitics as compared with human fibroblasts in tissue culture. ~
Because of this. Gal-X activity was then studied in fresh specimens of benign,
inflarncd, and ncoplastic human bladder epithelium. Results showed that 40 V
auays on transitional cell carcinoma, both invasive and twninvasive, ranged
from 24.4 to 180.0 cpm/µg of protein (mean 70.3), and 50 aasays on normal
or inflamed mucosa ranged from 0.8 to 46.1 epm/Pg (mean 9.00). The ma-
jority of benign niucosal specimens showed some inflammatory changes, but
Ihat did not increase the level of Gal-X activity. These raults, which show
that human transitional cell carcinoma has increased Gal-X activity regardless
of tumor stage or grade as compared with benign transitional cell epithelium,
indicate that this increase may be useful in the development of diagnostic
fluoroimmune and radioimmunc techniques to detect transitional cell
carcinoma.
Flagen-Cook, K., Prout. G. R.. Jr., Plotkin, G. M., Gilbert, S. L., and Wolf G.
Surgical Forum 29:627-629, 1978.
Other support: National Cancer Institute.
From the Urological Scrvice, Massachuactts General Hospital, and the Depart-
ment of Surgery, Harvard Medical School, Boston; and the Department of
Nutrition and Food Science, Massachusetts Itutitute of Technology, Cambridge.
CYCLOPFiOSPHAMIDE-INDUCED ONCOGENIC TRANSFORMATION,
CHROMOSOMAL BREAKAGE, AND SISTER CHROMATID
EXCHANGE FOLLOWING MICROSOMAL AC7IVATION
Cancer chemothcrapcutic agenta may be unequaled for the purpose of
asscssing short-term mammalian tinue culture assay systems for their actual
ability to predict human risk of developing wnoer as a result of exposure to
certain compounds. This paper illustrates that whlle rycloptaaplsamidc does
not produce oncogenic transformation in the absence of a metabolic activation
system, signiftcant transformation does take place in the presence of an
exogeneous activation source. Cell culture with and without an exogenova
liver metabolic activation system was used to investigate the efToct of tLia
chemotherapeutic agent on oneo=enic tnnsformation and ehrornownial damagt:,,
including itscreased sistcr chromatid exchanges. As noted above, cyclophos-
phamidc did not prodtice any abnormalities in the absence of inetabolic ac-
16 17
tivation, but incorporation of thc activating system into the auays led to
significant transformation, chromosomal breaks and incrcascs in sistcr chroma-
tid exchangcs. The removal of glucose-6-phosphatc and nicotinarnide adenine
dinuckotido phosphate from the mctabolic generating systcm, however, com-
plclely climinatcd these aberrationa. According to thcsc results, it may bc
nccessary to incorporate somc activation procedure into any study utilizing
in vitro systems to detcrminc the potential human hazards :.: a particular
chemical.
Bencdict, W. F., Bancrjoe, A. and Vcakatesan, N.
Cancer Rcsearch 38:2922-2924. 1978.
From the Division of Hcmatology-0ncology, Department of Mcdicinc. Chil-
dren i Hospital of Los Angclcs; and the Department of f'cdiatrics, University
of Southcrn California School of Medicine, Los Angclca.
MUTAGENICITY OF CANCER CHEMOTHERAPEUTIC AGENTS
IN THE SALMONEL"/MICROSOME TEST
Many short-term assays have been developed recently to screen potential
chemical carciroQcns/mutagcns, and catsccr chcmotherapcutic drugs have
been considered partictilarly suitable for examining the relationships among
short-tcrm Irr vitro assays. In vivo urcioogcnicity studics and chemical carcino-
gencsis in man. In the present atudy, 17 cancer chcmotherapcutic agents were
tested for their ability to mutate SalmoneUa ryph(murium tester strains in the
Sdmonefla/microsome mutagcniciry tcst. Results showcd a high corrclation
between the mutagcnicity and carcinogcnicity of a given agent. Carcinogens
positive in the test were adriamycin, daunomycin. I-propanol-3,3'-iminodime-
thanesulfonatc, cydophoaphamidc, isophosphamidc, hycanthone, chlornaphazin,
nitrogen muuard, uracil mustard, melphalan, and thio-TEPA. Two known
carcinogcns, actinomycin D and bleomycin, were oot detected as mutageru.
The presumptivc noncarcinaicn, mcthoumatc, was negative in the test. How-
ever, tiloronc and 6-mercaptopuritsc, tentatively classified as noncarcinogrns,
were mutagcnic. In summary, these tats showed that I 1 of 13 of the chcmo-
thcrapcutic agenta that are carcinogenic were also mutagenic in the Safmonclla/
microsome system. In addition to being carcinogenic in animal studies, somc
of these agents arc suspected of being carcinogenic in man.
tkncdkt. W. F. et d.
Cancer Rexarch 37:2209-2213, 1977.
OtAer aupportr National Canoer Institute.
From the Division of Hematology and OPcology. Department of Medicine.
Children's Hospital. Los Angeles; and the Department of Biochemistry, Uni-
versity of California. Berkeley.
CELL CYCLE-SPECIFIC ONCOGENIC TRANSFORMAT7ON OF
C3N/ 10T~/i CLONE 8 MOUSE EMBRYO CELLS BY
1-.8-D-ARABINOFU RANOSYLCYTOSI.NF
~ : .\n .... ,oi .. ... ..._.... _
..-
rcplicacion in prcierc:..:c to repair syntbcsia. 1':ar:icr uudics by
various investigators show that it can also be (ncorporated, although not ex-
tcnaivcly, into DNA, that it produces cell cycltspccific chromatid breakage,
induces chromosomal abberationa, is mutagrnic to mammalian cells, and
intcrfcro witn the rynthcsis of glycoprotcins and glycolipids. It is also
capable of causing malignant transformation in cultured hamster embryo cells
and in rat cclls. This report +Dows that the nucleosidc also induces oncogenic
transformation in the C311/ 10TSh CL8 line of tnouso embryo cells and that
this transforn ation is primarily S-phasc spocifk. Cell lines derived from type
I11 transformed foci grew in soit agarose and produced turnors in immuno-
suppressed syngcneic mice. In a11s synchronized by postconfluent growth
inhibition or isolcucinc deprivation, transformation was cell cycle dependent.
Maximal transformuion was observcd in cells treated in the S phase, although
some transformation occurred in ccils treated in the G, phase. The authors
indicate that sonx of these results m.y be cxpiaincd by the fact that ara-C
is capable of causing chromosomal lesions in the G, phase and of delaying
the entry of G, cells into the S phase. iluy also auggeu that speci& chronw-
somal changes may be particularly imponant in chemically induced malignant
transformation, especially since the cxpraaion of cancer in cells tranaformcd
by ara-C is associated with specific chrornc,somal imbalancss.
Jones, P. A., Baker, M. S., Bertram, l. S., and Benedict, W. F.
Cancer Rerearch 37:2214-2217,1977.
Other support: Natioual Cancer Institute.
From the Division of Hematology-0ncology. Department of Mcdicinc, Chil-
dren's Hospital, Los Ar.gdes; and the Dcpartm~t of Expcrinxntal Thcrapcu-
tics, Grace Cancer Drug Center. Roswcll Park Memorial Institute, Buffalo.
SPECIFICITY OF HUMAN, RAT AND MOUSE Si.iN EPOXIDE
IIYDRATASE TOWARDS K-KEGION EPOXIDESOF
POLYCYCLIC IfYDROCrRBONS .
Microsomal cnzymcs have the capacity to ttansform aromatic and
olcfinic compounds includiaz bcnzo(a]pyrcnc to epmtidca which arc c1w
trophilic and can spontanco,uly form covalent bonds with the mKkop?tilic
moictics of tissue DNA, R21A and protein. Several stadics have shown that
cpoxidc hydratase has a uniq,x role in the metabolic lormation of carciro-
gcns from polycyclic hydrocfArbons. This report cnumeratcs some of this
cnzyme i properties in humar, rat and tnouse akin micro.ornal fractions aad
compares them to those foun.lln liver preparations. The skin enzyme hydrated
all epoxidcs tuted, with humin fractions showing the ma: activity, followed
IE 19
