Council for Tobacco Research
1980 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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- 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]
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- CTRMN004684-4686 Meeting of the Executive Committee of the Scientific Advisory Board New York, New York June 11, 1976 [St]
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- 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
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- ANNUAL REPORT
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1980 REPORT ~
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THE COUNCIL FOR TOBACCO RESEARCA-U.S.A., Inc.
T1lE COUNCtL FOR TOBACCO RESEARCR-U.S.A., Inc.
110 East 59th Street, New York, N.Y. 10022
SCIENTIFIC ADVISORY BOARD
to The Council for Tobacco Research-U.S.A., Inc.
as of December 31, 1980
SHELDON C. SOMMERS, M.D., Chairman
Director of L.ahoratories, Lenox Hill Hospital
Clinical Professor of Patholosy
College of Physicians & Surgeons of Columbia University
New York. New York
RICHARD J. BING, M.D.
Director of Cardiology and Intramural Mrdicine
Huntington Memorial Hospital, Pasadena, California
Pro(essor of Medicine
University of Southern California School of Medicine
Los Angeles, California
ROSWELL K. BOUTWELL, Ptt.D.
ProJrssor of Oncology
McArdlc Laboratory for Cancer Research
University of Wisconsin
Madison, Wisoonsin
JOSEPH D. FELDMAN, M.D.
Head, Department of Immunopathology
Scripps Clinic and Research Foundation
I.a Jolla, California
WILIJAM U. GARDNER, PH.D.
Scientific Director, The Council for Tobacco Rcscarch-U.S.A., Inc.
E.1C. Nwu Pr%ssor of Anaromy (emeritus)
Yale Univcrsitr School of Medicine
New Havea, Cooaocticut
ROBERT J. HUEBNER. M.D.
Chie/, Laboratory of RNA Tumor Viruses
National Canctr Institute
Bethesda, Maryland
LEON O. JACOBSON, M.D.
Joseph Regenstein ProJessor of Biological Sciences
Univusity of Chicago
Qticato, IUinoia
I iEN RY T. I.YNCi I, M.D.
Professor and Chairman
Dcpartmcnt of Prcvcntivc Mcdicinc and Public Ifealth
Crcighton Univcrsity School of Medicine
Omaha, Nebraska
HANS MEIER, D.V.M., Dr. Mcd. Vct., M.R.S.H.
Senior S(a/J Scientist
The Jackson Laboratory
Bar Harbor, Maine
GORDON H. SATO. Pu.D.
I'roJessor of Riol)Ry
University of California, San Diego
La Jolla, California
Scienti6c StaR of The Couneil
WILLIAM U. GARDNER, Ptt.D.
Scientific Director
ROBERT C. HOCKETT, Ptr.D.
Research Director
DONALD H. FORD, PH.D. VINCENT F. LISANTI, D.M.D.
Associate Research Director Associate Research Director
DAVID STONE, PH.D.
Associate Research Director
t
.
CONTENTS
(ntroduction
, , , , , , , , , , , , , , , , , , 5
Abstracts of Rcports . . . . . . . . . . . . . . . . 7
CanccrRelatcd Studies . . . . . . . . . . . . . 7
The Rcspiratory Systcm , . . . . , . . . . . . 29
Heart and Circulation . . . . . . . . . . . . . 41
Neuropharmacology and Physiology . , . . , . . . . 49
Pharmacology and Biochemistry . . ... . . . . . . 57
Immunology and Adaptivc Mechanisms . . , . . . . 69
Epidemiology . . . . . . . . . . . . . . . . RO
Active Projccts . . . . . . . . . . . . . . . . . . 90
Completed Projects . . . . . . . . . . . . . . . . 99
Index of Principal Investigators . . . . , , . , . . . , I I I
Index of Senior Authors . . . . . . . . . . . . . . 112
Introduction
Since i1s formation 27 years ago, the Sciemifx: Advisory Board to The
('ouncil for Tobacco Rc.scarch-U.S.A.. Inc., has rcvkwed many formal and in-
lormal applicaturns tur rcxarch support. The direct result is that 413 diflercnt
proj.cts havc Ixen lunded by 'fhc Council. based upon the rccommcndations
ol the Adviwry Board, to support invc.tigaton in 259 medical schools, hospitals
and rescarch instinotions. Each of thcx projccts, whcther active or completed,
is listcd in this ycar's Report. Total funding through 191{0 was SMt.00q.0o0.
The chief output of The Council's financial support arc 1,14342 scientific
papers and repnrts. published by these investigators in many diQerent medical
and scicntific journals, cuvering a widc range of subjects. 'ihe puhlication of
thcsc rescarch results adds to the scientific literature and to the stockpile of
informauun (rom which. it is hoped. will conie answers to complex problems
.uch as thuse asociated with cancer, cardiovascular diseases and pulmonary
ailments. Abstracts of manuscripts published during 19K0 that .cknowkdged
Council snpport comprisr a section of this Annual Report.
During 198O two new memhars were added to the Scientific Advisory
Board to provide additional expertise to that dwinguishcd body. They were
Roswell K. Noutwcll, Ph.D., Prufessor of Oncology at the McArdk Laboratory
for Cancer Rescarch, University of Wiseonsin. Madison, and Gordon H. Sato,
Ph.D.. Proressor of t3iology. University of California. San Diego.
5
s
;
Abstracts of Reports
1'vrl6rwinl arc ah,lracts, appruvcd by thc aulMxs, ol rcports-on new
rrscarih :rckmowlctlging support Irum '1'hc ('ouncil that havc appcarcd in scicn-
utic luurnals srncc puhhcatiun of thc 1979 Kcport. Thc namc ol lhe recipicnl
is in ilali.c.
'1 hc ah.Iracts arc groupcd undcr thc.c headings: 1. Canccr-Kclatcd Studics,
II. '1 trc Kcspirataxy tiystcm, 111. Heart and Circulation. IV. Ncurupharmacology
and Physiology. V. 1'harmaculogy and Biochemistry, VI. Immunology and
Adaplivc Mcchaoisms. VII. I'pidcmiolugy.
I. Cancer-Related Studiea
ARYI. fIYDR(X'ARBON HYDROXYLASE IN NORMAI. AND
C'AN('EK I'OPULA'f1UNS
The rolcs of aryl hydrocarbon hydroxylase (AtiF1) and its inducihilily
in pulycycfic arumatic hydrocarbon carcinogcnesis arc discussed at length in
what is csscntially a review of the research in this area. With rccpect to human
AHlI. this groufis current views arc summarized as follows: (1) thc enzyme's
inducihilily diRers among various individuals; (2) this diBerencc is genetically
controlled; (3) thc distrihution paturn of Atilt inducibility in the normal
population may merely rclkct day-to-day variability in the lymphocyte system,
hut it also suggests polygcnic control of the cnzymc system; and (4) lung
and oropharyngeal cancer paticnls have a higher Atilt inducibility than that
found in the nurntal population. Indications arc, however, that cancer yrr u
docs not causc high Atilt inducibilily. In patients with othcr types of malig-
nancics. Utc cnzynte inducibility was indistinguishabk from that found in the
normal puptdatiun. Studies that show an increased incidence of hydrocarboo-
induccd tumors in animals susceptible to AHH induction, however. ><uggeu
that such inducrhilily is a critical factor in the occurrence*o( chemically in-
duced tumors. Ncvcrthckss, the dcvclnpment of a more reliable method ot
asscssing AtiH iru)ucihility in humans is prerequisite to the establishment of
this factor's role as a determinant of susceptibility to hydrocarbon-induccd
wniurs in man.
Arnatr, M. S.. Yamuchi, T. and Johnson. D. A.
In: Gri/lin, A. C. and Shaw, C. K. (eds.): Carcinogtn,: Idrnti(Kaion rurd
Merhunianu o/ Action, New York: Raven Press, 1979, pp. 145-156.
Oth.r auppurt: National Institulc of Gcneral Medical Sciences and National
Cancer Institute.
Front the Dcpartmcnls of Biulogy and Biomathematics. The University of
Tcxas System C'anccr ('enter. M.D. Anderson Hospital and Tumor Inslitute;
and the University ul I cxas Mcdical 5chuol at Houstun.
7
-1
ARYI. f1YDROC'ARBON HYDROXYLASE IN HUMAN CANCER
POPULATIONS
1he genetics of aryl hydrocarbon hydroxylase (Allll) inducibility and
tunwr susccptrbilily have becn studicd extensively in inbrcd roicc, and sumc
of thc exlxrimcntul animal modcls have suggested that AIIII inducibility could
bc an im)wrtan( dctcrntinant of susceptibility to hydraKarhon-tnduccd Iurnurs
in humans. To tcst this hypothcsis. AFIH activity was measurcd in culturcd
human lymphocytes. One inveatigator, surveying inducrbility in a population
of 353 healthy donors, reported that it fcll into three groups: low, rntermedi-
ate and high. This trinsodal distribution suggested that two allcles at a.inglc
locus were responsiblc for the genetic control of AFI)f irxfucibility. Family
studies were cunsistenl with this concept. The present invcstigators nxa.rucd
AHit inducibility in lung cancer patients and paticnts with othcr typcs of
cancer, and dcvebpcd a sophisticatcd, computerized systcm lor infornration
rctricval pertaining to normal donors and cancer patienu. Over 7lX) normal
donors and 600 cancer patients, including approximatcly 250 with lung can-
ccr, have been sesred in this systcm so date. The studies reported here lead
to the following summary of AfIH inducibility in humans: (1) individuals
diHcr in their AHH inducibiGty; (2) the inducibility diRercnces observcd bc-
twecn people arc under genetic control; (3) the unimodal distribution of AIIII
inducibility observed in the normal population may stem in part from day-to-
day variability in the lymphocyte system, but also suggests polygcnic control
of /he enzynu system; and (4) lung and oropharyngeal cancer patients cx-
hibit higher AHH inducibility than the normal population. No cause and
effect relationship can be inferred from these studies alone, but viewed in the
wntext of what has been shown clearly in experimental animals, the human
lymphocyte AHH studies suggest that AHH inducibility is an important dc-
tcrmiaant of susceptibility to hydrocarboa-induced tumors.
Arnort, M. S., Yamauchi, T. and Johnston, D. A.
In: Jones, P. W. and Leber, P. (eds.): Polynwrlear Aronratic Nydrorarhon.r,
Ann Arbor Science Publishen, Inc., 1979, pp. 779-791.
Other L.pport: National lastitutc of General Medical Sciences and National
Caocer Inststute.
From Ihe Departmcnts of Biology and Biomathemalics, The University of
Tcxas System Cancer Center, M.D. Anderson Hospital and Tumor In,tiwrc;
and The University of Texas Health Science Center, Medical School at Houston.
ARYL HYDROCARBON HYDROXYLASE ACTIVITY IN PULMONARY
ALVEOLAR MACROPHAGES AND LYMPHOCYTES FROM LUNG
CANCER AND NONCANCER PATIENTS: A CORRELATION WITH
FAMILY H)STORIES OF CANCER
In tbis attempt to determine whether differences in aryl hydrocarbon
hydroxylase (AHH) iaducibility cxist bctweca normal and lung cancer pa-
tients. AHH activity was measured in pulmonary alveolar macrophages
(PAMs) and peripheral blood lymphocytes from cigarette smokers with and
without prim.ry luug canccr. The data allowed comparisons between the nor-
mal and lung cancer paucnts for 26 variables, including age, occupation. sex.
and sanrily hisluric% uf tliscase. Frequency distribution analy.is of AH11 in-
rluctino rrt~us fur thc Iwo gruups rcvcalcd an incrcascd number of individuals
rn the lung canccr paucnl group wi/b high lymphocyte induction values. Such
nn incrca.c was nw shown lor high-I'AM AIIII values in lung cancer patients.
When individual I'AM aud lymphocyte AH11 values were compared between
nuncanccr and lung cancer patients, there was a positive correlation for nun-
cancer paticnu, hrut ,hesc values did not correlate for lung cancer paticnta.
'lhcx cancer paticnts were divided into three subgroups showing (1) high
PAM and low lymphocyte AiIH levels, (11) low PAM and low lymphocyte
A)Ilf lcvcls, and (I11) low PAM and high lymphocyte AIIII kvcls. When
the uicidcnce of lamily histary of cancer was compared for these subgroups,
none was rccordcd for pcr.uns in subgroup ll; howevcr, individuala in sub-
groups I and III prcccnted family cancer history incidences of 9.5% and
i9.1%, respeclivcly. Paricnts in group 111 averaged six yean younger than
thasc in gruup 1. ') hcsc data support the hypothesis that high kveb of AHH
might be associated with increased levels of lung cancer in man, and they
indicate that, for the analysis of AIIII levels in lung cancer patients, usc of
the cultured lymphocyte system as a sole indicator of high Alfll levels is not
warrantcd. These data also indicate that genetic factors are expressed in the
initiation of lung cancer.
McLcmorc. T. 1.., Murrin, R. R., Springer, R. R., Wray. N.. Cantrell, E. T.,
and Bushcc, D. L.
lJiochernical Genetics 17(9/ 10):795-805, 1979.
Other arrppurl: National Inaitutes of Health, National Cancer Instilute,
Anxrican Cancer Society, and the Veterans Administration Hospital, Houston.
Fruns the Department of Mcslicine, Baylor College of Medicine. Houston;
Vetcrans Administration Hospital, Houston; Department of Pharmacology,
l'cxas ('ullcge ua Ostcupathic Medicine, Fort Worth; and the Departmeat of
lliological ticicnces and the Genetics Center, North Texas State University.
Denton.
DO1E-RFSPONSE RELATIONSHIP OF RAT ARYL HYDROCARBON
)IYDROXYLASE AND EPOXIDE )IYDRATASE INDUCTION
The data reported here support the hypothesis that different regulatory
mechanisms control aryl hydrocarbon hydroxylase (AHH ) and cpoxide hydratase
(EH) activity and that a selective inducer of liver enzymcs, such as phcao-
barhital, may also aflect the inducibility of extrahepalic monooxygenases by
other chemicals. The AH)f in rat lung and kidney is highly sensitive to in-
ducers in cigarette smoke and smoke condensate, while EH activity is not af-
fected by Ihcse agents. Both AHH and EH can be induced selectively in pri-
mary rat liver cells in culture. Low doses of bens(o)anthraccrse (BA) prefer-
entially enhance A)fll activity, while tranr-stilhcnc oxide (TSO) and various
g 9
c
antioxid:rnts aQcct only the EH activity. Phenobarbiul, which polcntirtcs in-
duction of lung AHH activity by low doses of henzo(a)pyrcne,also induccs
AHH activity in cell culture and has a greatcr than additive effect when mixcd
into the culture medium with BA. The effect of phcnoharhital on AH11 induc-
tion is blocked by TSO but not by the inducing effect of BA. 7lrese results
suggest that phcnobarbital is not merely an AF1)l induccr, but also has the
capacity to potentiate /hc action of chemicals that belong to a ditTcrenl class
of induccrs. In particular, they demonstrate that phcnobarbital ak,ne induccs a
cytochrome P-450 linked AHH and causes the accumulation of more cyto-
chronx Pr-450 associated enzyme when mixed with BA.
Gitkn, !. E. er ol.
Archivra o/ To.lcoloQy Suppl. 3:209-216, 1980.
From the Laboratoire de Chimie MEdicale, Institut dc Pathologie. UniversitE
de Li2ge, Litge, Belgium.
COMPARISON OF ARYL HYDROCARBON HYDROXYLASF. AND
EPOXIDE HYDRATASE. I.NDUCTION IN PRIMARY FETAL RAT
LIVER CELL CULTURE
The effccts of benrla)anthracene (BA), phenobarbital (PB), cigarette
smoke condensate (CSC), 2,3,7,B-tctrachlorodibenzo-p-dioxin (TCDD) and
rrars-uilbcne oxide (TSO) on aryl hydrocarbon hydroxylase (AHII) and
epo:ido hydratase (EH) activity have been studied in primary fetal rat liver
cell eukure. The two enzymes vary in their response to these chemicals as
shown by the following: (1) the concentration of BA, PB and CSC required
to induce AHH is lower than the one nec+dcd for signi&ant induction of EH;
(2) TCDD and low concentrations of BA selectively induce AHH; (3) with
BA. PB and CSC, the AHH inductioa kinetics are not the same as those of
EH induction; (4) TSO induces EH selectively. In the early phases of F.H
induetion, RNA and protein synthesis as well as the continuous presence of
the inducer arc required. When EH activity reaches a plateau, neither imact
RNA rsor protein synthesis is required to maintain enzyme activity at its opti-
aul kveL Tbe EH activity decays with the removal of the inducer, and its
biologic half-life is estimaled to be about 72 hours as opposed to about 10
hours for AHH. While TSO preveMs the induction of AH11 by PB. it does
not block that mediatod by BA aod CSC; but added together with PB, BA,
CSC or PB plus BA, it induces the EH activity in a more than additive man-
ncr. This effect, however, is only seen after six days of continuous treatment.
According to these results, in this particular tissuo culture model, the mech-
aoam of AHH and EH induction can clearly be disaociatcd.
Goujon. F. M., V.ar Canrfort, J., aad GkJrs, I. E.
Ckenrko-8ioloXiraJ lnrrract(arr 32:361-375, 19g0.
From the Laboratoire de Chimie MEdicak ct Toxicologic. lnstitut dc Pathologic,
UnivenitE dc Li2=e, Litgc, Belgium.
CORKIi1.Af1ON OF INDUCIBILITY OF ARYL HYDROCARBON ~
ItYnROXY1.ASt: WITff SUSCEPTIBILITY TO 3-METHYLCHOI.AN- O
'I IIRL:N1:INDUCI:D LUN(i CANCL'KS
Intrarrachcal trcatmcnt with polycyclic aromatic hydrocarbons rnay in-
duce spccific genctic regulation of AHll activity. Previously used melhods for
prcx)ucing lung carcinomas in inbted strains of mice sugacst a puuible animal
modcl in which the susccptibility to pulmonary carcinomas may be specifically
linked to the capacity of that organ to metabolize chemical carcinogens. In the
system dcscribcd here, mice of the C57BL/6Cum. DBA/2Cum, first filia
(F,) and hackcross progeny from the two parental strains were evaluated for
susceptihility to 3-methylcholanthrene (MCA)-induced lung cancers. In the
crosus, Afill respumivcncss segrcgatcd as a single autosomal dominant gene
(Ah locus). The Aflll responsive mice expressed a very much higher AI1F1
activity/g wet weight liver after intraperitoneal treatment with MCA than the
nonrespunsivc animals. Intratracheal administration of M('A (four 500 mg
doscs, at wcekly intc(vals) caused a variety of pulmonary malignancies among
the mice surviving one year aftcr treatment, including squamous cell carci-
nomas, alveolar adcnucarcinomas and adenosquamous cell carcinomas. The
ALIH-resp,)nsive ('S7Hl./6Cum, F, and CS7BIa6Cum x F, mice were much
more susceptible to MCAinduced lung cancers than the nonresponsive DBA/
2Cums. Purthcrmure, thc lung cancers found in DBA/2Cum x F, backcruss
progeny did not occur randumly, since significantly more tumors were found
in thc Alifl responsive oR.pring than in the nonresponsive ones. These data
tend to support the exrstence of a genetic link between the capacity to respo
to polycyclic aromatic hydrocarbons through irxreased kvets of AHH activit .
and susceptibility to certain types of malignancies. Indications are that sus-
ceptibility to MCA-induccd lung carcinomas is relatcd to the AM allek. These
results also suggest that animal models involving inbred strains could be used
to surdy the control and regulation of cpithclially derived tunwrs, the type
most frequently observed in the' human lung.
Kouri. R. E. cr al. (MicrubiofoRicoJ Astociarrt, Inc.)
Canctr J.rucrs 9:277-:84, 1990.
Otber arrppurr: National C'ancer Institute.
From the Departmcnt of Biochemical Oncology and Department of Experi-
mcntal Oncology, Microbiological Associata, Inc., Bethesda, Md.
XENO7 ROPIC VIRUS EXPRESSION AND SUSCEPTIBILITY TO
3-METHYLCHULANI HKL'NE-INDUCED CANCER
Mice from two inbred strains, NZB/BLNJ and 1?9/1, and their various
gcnetic crosses were studicd here for evidence of a geperic linkage between
spontanuus production of infectirws xenotropie (X-tropic) virus and suscep-
tibility to chemically induced cancers. The parental strains and F backcruss.
and F_ progeny between lhcse two strains were partially spknectomized to as-
ccrtain X-trupic viral sutus and were subsequently treated subcuuneatsly with
500 pg of 3-merhylchulanthrcne in trioctanoin. Progeny from second back-
crosses were also tested for their X-tropic viral stattrs and susceptibility to
3-nxthykholanthrene carcinogenesis. All mice were observed for evidence of
.~.
wL.
c
t
6brosarcornas at the site of inoculatirw over a IO-month pcriud. In order to
.pccilically address thc quLstion of Ihe rok of X-Iropic virus cxpression on
susccptibility to chemical carcinogcneais, populations in which virus cxpressiun
aegrcgates were studied. Here, the careinogenicily of the chemical was dclcr-
minesf by obtaining a single value, the C1, which utilized both tumor incidence
and latency pcriod. After 3-rrrethykholanthrcne Ircatment, 42% of the virus-
positive mice devebped tumors as compared to 22% of thc vints-negativc
animals. However, the average latency period was much longcr for the virus-
positive mice, so that the resultant CI's for the two populations wcrc quite
similar. Overall, the results seen herc suggest that little, if any, correlation
exists between virus expression and 3-mcthylcholsnthrenc carcinugcncsis, and
that there is no demonstrable genetic linkage between the two.
Nayar, K. T., L.evy, J. A., O'NcDl, B., and Kouri, R. F. (Microbiological
Atsociatts, Inc. )
Cancer Rrisarcb 40:4364-4367, 1980.
From Geomet Technologies, Ine., and the Department of Biochemical On-
cology, Microbiological Associates. lrrc., Bethesda. Md.; and Canccr Rescarch
Irutitute, University of California School of Medicine, San Francisco.
COMPARATIVE EFFECTS OF INDOLE AND AMINOACLTONITRII.E
DERIVATIVES ON DIMETHYLNLTROSAMINE-DEMETHYI.ASE AND
ARYL HYDROCARBOIJ HYDROXYLASE ACTIVITIES
Certaiu substances such as the 3-substituted indole derivativcs found in
erueiferous vegetablq, including brussel sprouts, cabbage and cauliflower, alter
the biological responses to chemical cueirrogeas. Of these compounds, which
induce aryl hydrocarbon hydroaylase (AHH) and inhibit polycyclic hydro-
earboa-induced neoplasia, at least one, 3-indolymethanol, also irxhtces amino-
pyriac N-0emethylaae and /-nitroacisok O-0cmcthylase. indolc itself also in-
duces dirrscthylnitrosamioe (DMN)-demetAyWe I in the rat, as does trypto-
phan. Aminoacetottitrik, a mixed-function oxidase modifxr, intcr(eres with
DMN rsretabolism, inhibits DMN-induced mctby/ation of hepatic RNA and
breakage of DNA, and protects against DMN-produced injury to micrusomal
amino acid irrcorporatioa; it also ptotecta against DMN-induccd disorganiza-
lion o/ hepatic fine structure and DMN-induccd hcpatic carcinogcnesis. Itcre,
the eQata of indole and amfooacetonitrik derivatives on the two enzymic
forms of DMN-dcmethylase and on AHH were studied in vino. lndok, 3-in-
dolymethanol, 3-indolylacetonitrik, 3-iadolylacetone and L-tryptophan in-
creased AHH induction 3- to 6-fold, but P-3-irsdolykthanol had no e/fcct. In
tact, the latter decreased the tissue endopfasmic reticulum content (i.e., micro-
sonsal protein/uait weight) by 21%. Only L-Iryptophan induced DMN-dernc-
thylase I and only it and 3-indolyrnethanol induced DMN-demethylase !1,
about doubling the enzyme activity in all three instances. Aminoacetonitrik
strongly repressed DMN-deroetbylaae I. Substitution of the amino group
greatly decreased or abolished mixcd-function oxidase repressor activity. For
uampk, iminodiacetonitrile displayed only about one-fifth the repressor ac-
tivity of the puent eompound, while nitrilotriacetonitrik and dimethylamino-
autoaitrik aeemed to be inactive. Neither the derivatives studied nor the par-
eat compound, however, had any efieet on DMN-dcmethylasc II or Allti
activitics. Since these nwxcd-function oxidases represent critical atcps in the
metabolism uf DMN and polynuclear hydrocarbons, the modifying eRects of
indole and aminoacctunitrile and their derivatives demonstrate the potential
complexity of asscssing thc efTects of dietary constituents on the carcinogenic
responses. It is suggestcd that such constituents can generally alter susceptibility
to chemical carcinogens and in some instances, can further amplify the ear-
ciiwgenic responscs to wu or more combination of agents.
.1 rcns, J. C. rr a!.
Cancer Letters 9:161-167, 198U.
Other aupp.ut: lloRmann-La Roche, Inc.
From the Scanun's Mcmorial Research Laboratory, U. S. Public Health Service
Ilospital; and the Dcparlment of Medicine, Tulane University Medical Center,
New Urleans.
111G11-PRL:S5UR1: LIQUID CIIROMATOGRAPIIIC ANALYSIS OF
BL:NZU(a)PYRENE ME,I'ABOI.ISM BY HUMAN LYMPHOCYTES
FROM DONORS OF DIFFERENT ARYL HYDOCARBON HY-
DROXYLASE INDUCIBILITY AND ANTIPYRINE HALF-LIVES
I.ymphocytcs from six human donors were evaluated by means of high-
pressure liquid chromatography (HPLC) for their ability to mctabolize
benzu(u)pyrene (BP). In these subjects. the aryl hydrocarbon hydroxylase
(AHH) inducihility ratio ranged from 2.4 to 4.6 and the antipyrinc plasma
half-life from eight to 17 hours. While the results show that BP metabolizing
activity docs not differ qualitatively among human donors, there are quantita-
bve variations in the inducibility of BP metabolites, reflecting known individual
differences in AHH inducibility. Several BP metabolites were identifscd: 7,8-
dihydrudiol,, quinoncs, and 9-hydroxy and 3-hydroxy phenols. The HPLC
data for the induction of BP phenol production correlated well with the known
AHli' inducibility ratios for the donors, as determined by the conventional
Iluorometric AIiH assay. These studics also indicated that the induction of
bcnzo(n)pyrcne-7,8-dihydrodiul, proposed as the proximate carcinogenic form
of BP, dues not parallel BP phenol induction. In addition, there was a strong
ncgative eurrclation Ixtwcen Afllf irsducibility and measurements ol plasnu
antipyrine or urinary 4-hydroayantipyrine half-Ide. At best then. AHH in-
ducibility can be presunud to be an indcx of the capacity to metabolize BP
through major, it not all, pathways, auggesting unequal flux of BP through
the various routcs. 7 hc data also indicate that at least one activating inter-
mediate sy.tem, the formation of BP-7,8.fiol, is not directly proportional to
A)lH levels.
Gurroo, N. L., Vaught, J. B., Marinellu, A. J., Paigen, B., Gessner, T., and
Bolarwwska, W.
Cancer Rrseareh 40:1305-1`310, 1980
Othrr aupport: U. S. Public tlealth Service.
From thc Dcpartruent ol Eaperimental Therapeuties and Grace (-arxer Drug
C'enter, and the Departmcnt ul Molecular Biubgy, Roswell Park Mcrrrorial
)mtftute, Burtaln.
12 13
(:AK('IN((if:Nl('l1Y 01: BI:N'L()(a)PYRI:Nii AND'1'IIIK'1'1:I:N OF I'f:S
1)I:KIVA'1'IVI:S IN ('3II. I('uns MICE
17rc tunwrigcniciry of a sclccted nunncer u( hcozo()pyrcnc (IIP) Jc-
rivalivcs was invostil;ated in a(urrNN modlI eon.sisting ol 6hHlsarcumr Indnc-
IilNl in sulKlltanclNl.\Iy injeclcJ (',i11/fCurn mice. lhc 13 derivatives uscd
were sclccleJ un the hasis of their in rirro and in riro biulogic activity, as well
as of their potential for cltkidating Ihc :mportancc of fls'7,11-diul-'/.lt)clwxidc
in nrcdialing tumor /ormati.m following suhculancuus Ill' adminislraunn. '1 hc
rCSrdls xrrgges/ /hur urducrion of sulautaneuus librasattuaw'. /n 1111% rnau.c
suain ha% mtp.atant limitalions In apile of BI''s abdity to cau.c a high incir
dcr>Le of umu.rs. Mosl signilkanlly, the derivativcs' /wlaiity wppcars ru maik-
cdly altcr Ihcir biologic activity in Ihlt system. Ikcausc n><IaMili/cs of poly
cyclic hydnkarlxtns arc usually more polar than thcir parcnt compotmJ, it is
d,0icull to assign a particular onc to the status o( proximate or uhimatc car-
einngen. In aJJition, with any givcn compound, the tnmur incidcncc was
maahly aRecleJ by the nature of the snlvent. For example, ItP'% carcinogeni-
cily index decrcascd ahour SO-70"b whcn DMSQ was uscJ as the vchiclc rather
than Irioctanoin. On the other hand. othcr investigators have found that it
was almost completely abolished in a 1:1 trioctanoin and hccswaR mixturc.
BP-7,g Jinl-9,10-
According to some previous reports, tumorigcnicity of
epoaidc diastercomus on mouse skin also depends on the solvent empktycJ,
the highest irrcidence having heen observed with IctrahyJrofuran and with
acctone. Both of these, howevcr, proveJ to be toxic to micc. Additional re-
seareh may lead to the discovery of a solvent or solvent combination that mini-
mizes the eRecl of a compound's polarity in determining tumor response.
Ktwri, R. E. rr al. (MicroAioloxicd Associari, Inc.)
lourrrd oJ rhr Narionaf Cancer Irrrtirurr 64(3):617-623, 1980.
From the Departmcnt of Biochemistry and Drug Mctaholi.m, Hof(mann-l.a-
Roche, Ine., Nutky, NJ.; the Department of Biochemical Oncology. Micro-
biological Associates. Inc.; and the Section of Oxidation Mcchanisms, Laboratory
of Bioorganie Chemistry. Nuional Institute of Arthritis. Metabolism, and Digct-
tivc Diseasa, Bcthcsda, Md.
SECONDARY METABOUSM OF BENZO(a)PYRENE IN HUMAN CELLS
Whik many metabolites of benra(a)pyrcrre (BP) are known to form in
man, recent studies have shown that these primary metaM>aites are tnnsformed
further to conjugates of sulfate, glueuronide and gluthathionc. Here, human
lymphocytes and lung aucropiuges were used to study BP metabolism in
cancer and rroncarrcer patients. Results of these experiments showed a meta-
bolic profik similar to that reponed by others for human lymphocytes. After
hydrolysis of the fractiqu, the metabolic prohks were slightly altered. The
observed data suggest that during a short time of reaction where the substrate
concentration is not saturating the enzyme complea, a substantial amount of
conjugation occurs via glueuronide formation. The phenols are conjugated to
an equal extent with glucuronide and sulfate. Also, in lung macrophages the
extent of cunjudation wa% variable from pcr.on to person. A preliminary sur-
vcy of live non.rn,rkcr% indicatcJ Ihat the cxtent and sclccbvuv of mclahol-
isnm wa% variable a% well. Ihcre was no consi.tcnt pattern I.. the variation in
cunlug:uiun ot 111' metaMrlqe.. Overall the data presented in Ihit paper indi-
catc thal r:ulturrd humao lymphocylc, and pulmonary alvcular macrophages
have the capaaty to mctaholire BI' to several hydruxy and yuimme derivativa.
I he+c arc Iurthcr mclatwfizcd tu polar conjugates, including sullate and glu-
crutrnidcs. 'Ihc prvlwrtirrom ul tlrc varrouv primary mctabohtcs and conjugata
v,ny hctwccn indiv,Jual. and vary with Ihe time of incubation anJ I1P concen-
lu,uun in u smt;lc unDvnluut, Ibus incrcasmg and cumpnumhng the complexity
of 111' m.wbuthm in lwman tissucs.
C'unrrell, 1:. 'f: er ul.
Prrx'rrdinxs u( rhr Wrwrryi l'haruroculr.AY Sorierp 22:273-27h, 1979.
Other arr plrur(: U. S. 1'uhhc I Icallh Scrvicc.
From the North Icxas State Univer.ity Health Scicnces ('enter; College of
Osteopathic Mrdicine. 1`urt Worth. Tcc.; and M.D. Arnknon Hospital and
'funror Institute, IIuu.lun.
III?N'!.()/rvIPYRI:NI: M1:1'ABOI.ISM IN RAT FETAL HEPATOCYTES
('UI.TUKt. IMI'ROVI:D MI:l71ODOLOGY AND EFFECTOF
SUB.STKATIi C'ONCGNTRAI lON
l he exact ratc of henzollpyrenc (BP) metabolism in any living system
is important in that the balance between the various enzymatic reactions in-
vulvcd in this procc.s is highly significant in determining the intraccllular con-
centration of thc toxic intermediates. Presented here arc data on BP metabolism
in primary Ictal rat liver cell culture. The extent of in vivo 1sHIBP metabolism
was cslablishcJ by mcasuring all of the metabolites retained in the cell as well
a% tho.c cxcretcJ imu the culture medium. ihe extent of the conjugation and
thc nature of thc conjugatcs were determined and the metabolhe pattern was
analyzed by high pcrlurnrance liquid chromatography (HPLC). The fetal
hcpalucytes activcly nutaholize BP and readily excrete all the metaholites into
the culture medium as sullatcs and glucuronide conjugates. The relative pro-
portion of the laucr v.uic. dircctly as a function of the BP concentration. As
shown by the 111'I.(' analysis, BP-1,6-4uinonc and -3,6-quinune are the meta-
bohtes excretcJ in the largrst anrwrnt, suggesting the probaMe exictence of an
active G-hydruxyla.e rcactirm nkchanism in the felal hepatucytcs. Aryl hydro-
carhon hydroxyl.rsc :utivity mt>.htic% the overall rate of BP mctabolism Jn-
rnatically hut does nut allcct thc yua6tativc pallern of Ihe cxcreleJ metabolitcs
Van Cantforr, J.. Guujon, F. M. anJ Giclrn, /. E.
Chcnucu-Biuluyitrr! /nrrrucriuru _7i:147-/(r0 1979.
Front thc Lahnr;jtairc Jc Chimic McJicale, Institut de Pathologic, UniversitE
Jc Licbw, Licgc, Iklbwm.
14 1 t
G
0
PHAGOCYTOSIS OF ASBESTOS FIBERS BY HUMAN PULMONARY
ALVEOLAR MACROPHAGES
Although epidemiologic evidence supports a relationship between exposure
to asbcstor (AS) 6bcn and the incidence of cancer, the exact mechanism of
action on the human respiratory tract remains unknown. The pulmonary
alveolar macrophaga (PAMs), which ingest various foreign particles that
enter the distal tracheobrotschial tree, arc also the primary line of defense
against inhakd AS fibers, but because it is virtually indcstructible, this material
poses a unique problem tor PAM detoxification. Therc is cvidcnce, however,
that phagocytosis followed by coating of the particles with cell membranc
components, acid mucopolysaccharida and hcmosiderin convert it to a less
toxic form. The present study investigates some biological interactions buwccn
cultured human PAMs and amosite AS. Phagocytosis, cytotoxicily and ccll
surface changes were examined by scanning ekctron microscopy after the
cells' viability bad Arst been determined by the trypan blue dye exclusion
method.. Results show tbat low concentrations of amositc AS are only slightly
toxic to human PAMs in vitro. Higher coocentrations, however, cause significant
tosicity. Phagocytosis begins immediately upon contact with AS: the PAM
either wraps itself around the end of the fiber, endocytizing it by slowly moving
toward its opposite end, or it spreads toward each end from the midline, then
completely engulfs it. The macrophage membranes arc also aRectcd, as re-
tlectcd by an increase in cytoplasmic bkbbing known as zciosis that probably
results from the ccU's high metabolic activity, and by the appearance of a
fibrous-likc material in close approximation with the AS fibers in the arca of
the PAM membrane where the initial contact is made. The precise nature of
this cellular product is currently under study to determine its biochemical
structure. Further research into these biological interactions may prove valuable
in establishing the etiology of ASrctated lung disorders.
McLemore, T., Corson. M., Mace, M., Arnorr, M. S., Jenkins, T., Snodgrass,
D., Jlfarriw, R., Wray, N., and Brinkky, B. R.
Cancer L.rrcra 6:1i3-192, 3979.
Orbtr asrpport: Veterun Administration Hospital and the National Institutes
of Health.
From the Veterans Administration Hospital; the Department of Biology. Ttte
University of Texas System Cancer Center; M.D. Anderson Hospital and Tumor
Institute; and the Dcpartments of Medicine and Cell Biology, Baylor Collegc
of Medicine, Houstoa.
IN VITRO ACTIVATION OF CIGARETTE SMOKE CONDENSATE
MATERIALS TO THEIR MUTAGENIC FORMS
Accordin= to this report, both lAl and 2A1 reference cigarettes contain
subslrates for bepatic morrooxygenascs capable of generating metabolic inter-
rnediates that are mulasenic for S. rypbimuriwm tester strains TA1538 and
TA9E. Tbc latta is selectively more scnsitive to mutagcncsis induced by smoke
condensate. Thc most mutagcnic fractions, moreover, are not Ihe ones that
contain polycyclic aromatic hydrocarbons (PAH) but those suppoaedly con-
taining such hasesolublc chemicals as aromatic amines. The data suggest,
therefore, that most (about 5896 ) of the total mutagenk activity of these con-
dcnsatcs lies in the basic fractions and not in the ones containing the PAH.
In addition, mouse pulmonary tissues seem capable of activating certain PAH
and aromatic amincs but not others. Mouse, rat and human pulmonary tissues
arc currently being compared for their ability to metaboiically activate cigarette
smoke condensate material to biologically active forms.
Kouri, R. E. rr af. (Microbiofogica) AJSociarrr, Inc.) and B.nrdirt, W. F.
In: Water, M. D. rr at. (cds.): Applicarions o/ Stiorr-Tarm Bioauayi in r6r
Fractionation o/ Complrx Environmental Aliitwrrf, New York: Plenum Pub-
fishing Corp, 1979, pp. 497-512.
From the Department of Biochemical Onocology, Microbiological Associates,
Inc., Bcthesda, Md.; and Children's Hospital of Los Angeles, Los Angeles.
ORGAN SPECIFICITY OF INDUCTION OF ACTIVATING AND
INAC"1'IVA'fING LN"LYh1ES BY CIGAREITE SMOKE AND CIGARETTE
SMOKE CONDENSATE
The effccts of cigarette smoke and cigarette smoke condensate on the
activating and inactivating enzyme systems of the body were studied here by
in vivo and in ritro methods. In the rat, cigarette smoke inhalation selectively
induced lung and kidney aryl hydrocarbon hydroxylase (AHH) activity. On the
other hand, epoxide hydratasc (EH) and glutathione S-transterase were not
significantly modified in any tissues of the treated animals. Compared to the
kidney AH1f, the lung hydroxylase was three-four timcs more sensitive to small
concentrations of cigarette smoke and seemed to have a longer biological half-
life. In both tissues, the induced AHH presented the same in vitro sensitivity
to various inhibitors as a polycyclic hydrocarbon-induced AHH. In the in vitro
studies, cigarette smoke condensate fractions (CSCF) induced both AHH and
EH activity in primary (etal rat liver cell cultures. Neverthekss, the AHH
activity responded faster and to lower concentrations of CSCF than did the
F.Ff activity. A low concentration of bcnz(a)anthracene induced only the AHH
activity, while trunr-stilbcne oxide enhanced selectively the Eli activity.
Appropriate conccntrations of CSCF or of phenobarbital determined a parallel
induction of both enzymes. It seems, therefore, that the liver cell culture
constitutes a unique tool for a comparative study of the A111i and Eli in-
duction nxchanisms. The existence of coordinated or independent biochemical
control of AFtH and EH activity is discussed in this paper.
Gielrn. J. E. rr. al.
Arrhiwr o/ 'I'o.rirulu9y, Suppl. :(Mcchanism of Toxic Action on Some Target
Organs), 239-231, 1979.
Other aupport: Fonds National dc la Rcchcrche Scicntifiquc Mtdicak.
Front the l.atwratoirc de ('himie Mcdicale. Insurut dc Pathologic, Li2ge, Belgium.
17
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