Tobacco Documents Online

~ V Future Plans: The project plans to expand its activities in an effort to reach and influenc~ more dentists to assume their role as "educators for health." In addition, plans are to develop and implement a dental health education demonstration project with a dental society. Such a project would include a health educator working for the dental society, who would be responsible for coordinating the society's dental health program. This would include liaison and program develop- ment with other community organizations, schools, health organizations, etc. The health educator would also be responsible for organizing and conducting continuing education programs for dentists, dental hygienists, and dental assistants in the area of dental health education. Hopefully, such a project would serve as a model for other dental societies to incorporate into their ongoing programs. Project Dates: June 1967-1970. Source of Financial Support: HEW, PHS, NCSH (PH 86-67-242). Reference: (1) Weir, J. M., Dunn, J. E., Jr., et al. "Smoking and Oral Cancer: Epidemiological Data, Educational Responses." American Journal of Public Health 59(6), June 1969. 6. AMERICAN HEALTH FOUNDATION 180 East End Avenue New York, New York 10028 PrincipalInvestigators: Udo Wagner and T. Theis. Project Title: Physical Properties of Cigarettes and Chemical Composition of Smoke. Objective: To study relationships among leaf characteristics and smoke components. Methods or Approach: Using flue-cured tobacco samples from 20 stalk positions of four different varieties, cigarettes will be made and the physical properties of these cigarettes and chemical components of cigarette smoke determined. Determinations will be made on total particulate matter, nicotine, acetaldehyde, acrolein, formic acid, phenol, HCN, pyrene, benz(a)anthracene, and benzo(a)pyrene. These data will be subjected to a computer to evaluate the relationship between smoke constituents and leaf characteristics. Studies on leaf tobacco itself will be con- ducted by in-house research. Project Dates: June 1969-December 1971. Source of Financial Support: USDA, ARS, CRD (12-14-100-10283 [34] ). 7. AMERICAN HEALTH FOUNDATION Health Research Laboratory 180 East End Avenue New York, New York 10028 Principal Investigators: D. Hoffmann and P. Chan. Project Title: Identification of Tumor Initiators in Cigarette Smoke. Objective: To identify tumor initiators in cigarette smoke and conduct bioassays on mouse skin with fractions of the smoke condensate. Methods or Approach: The neutral fraction BI amounts to about 0.6 percent of cigarette "tar" and contains the majority of the tumor initiators from tobacco smoke (Science 162:862, 1968). 4

Subfractionations of BI led to several portions with tumor-initiating activity on mouse skin. The components in these fractions are at present isolated, identified, synthesized, and bioassayed on mouse skin for their overall contribution to the tumorigenicity of BI, the neutral portion of the "tar" and the whole "tar." I Results to Date: The following have been identified in BI: More than 30 polynuclear aromatic hydrocarbons, some of them carcinogens and/or tumor initiators; carbazoles and indoles; chlorinated hydrocarbon insecticides and some of their major pyrolysis products; esters of fatty acids; and quinones. Future Plans: Identification of mouse skin tests of newly identified BI constituents. Project Dates: January 1966-1973(?). Source of Financial Support: ACS. References: (1) Hoffmann, D. and Rathkamp, G. "Chemical Studies on Tobacco Smoke. V. Quantitative Determination of Chlorinated Hydrocarbon Insecticides in Cigarette Tobacco and Its Smoke." Beitrage zur Tabakforschung 4(5):201-214, July 1968. (2) Hoffmann, D., Rathkamp, G., et al. "Chemical Studies on Tobacco Smoke. VI. The Deter- mination of Carbazoles in Cigarette Smoke." Beitrage zur Tabakforschung 4(6):253-263, November 1968. (3) Hoffmann, D. and Rubin, J. "Chemical Studies on Tobacco Smoke. I. The Quantitative Determination of Indoles in Cigarette Smoke." Beitrage zur Tabakforschung 3(6):409-414, September 1966. (4) Wynder, E. L. and Hoffmann, D. "Experimental Tobacco Carcinogenesis." Science 162:862-887, November 22,1968. 8. AMERICAN HEALTH FOUNDA'I'ION Health Research Laboratory 180 East End Avenue New York, New York 10028 .PrincipalInvestigators: D. Hoffmann and P. Chan. Project Title: Tumorigenic N-Alkylated Heterocyclic Hydrocarbons. Objective: To identify tumorigenic N-alkylated heterocyclic hydrocarbons in the respiratory environment, and investigate the correlation between tumorigenic activity and chemical configura- tion of N-alkylated heterocyclic hydrocarbons. Methods orApproach: Methods include isolation of neutral N-alkylated heterocyclic hydrocarbons from cigarette smoke and organic air pollutants by chromatography on alumina, Sephadex, and gas chromatography; identification by ultraviolet spectra, infrared spectra, and mass spectra; and testing for tumorigenicity of identified agents on mouse skin and subcutaneous tissue of mice. Results to Date: Results show that cigarette smoke contains, in subfraction BI, the neutral components N-alkylindole and N-alkylcarbazoles. In addition, 1-methylindole has been found to be a tumor initiator and 9-methylcarbazole a tumor promoter: Future Plans: To test other N-methyl indoles and N-methylcarbazoles on mouse skin, and investi- gate reaction in tissue culture of 1-methylindole and 1-methylcarbazole, and the precursors for N-alkylated heterocyclic hydrocarbons in tobacco. Project Dates: July 1968-1972. 5

Source of Financial Support: American Health Foundation. Reference: (1) Hoffmann, D., Ratlikamp, G., et al. "Quantitative Determination of 9-Methylcarbazoles in Cigarette Smoke." Analytical Chemistry 41(10):1256-1259, August 1969. 9. AMERICAN HEALTH FOUNDATION Health Research Laboratory 180 East End Avenue New York, New York 10028 Principal Investigators: D. Hoffmann and E. L. Wynder. Project Title: Model Studies for the Reduction of the Tumorigenicity of Cigarette Smoke Con- densate. Objective: To reduce the tumorigenicity of the particulate matter of cigarette smoke, and explore mechanisms which lead to the reduction of tumor initiators and tumor promoters. Methods or Approach: Methods include (1) chemical-analytical studies and bioassays of the main- stream smoke of cigarettes made from different types and special varieties of tobacco, tobacco sheets, extracted tobacco, and tobaccos with additives; and (2) correlation between chemical- analytical data from the mainstream smoke, and tumorigenicity and tumor-promoting activity of the particulate matter with chemical-analytical data from-the tobacco. Results to Date: The tumorigenicity of tobacco smoke condensate can be reduced by selection of tobacco, selection of stalk position of tobacco leaves, use of tobacco ribs and stems, tobacco sheets and modifications in the tobacco sheet preparation, and use of additives. The nitrate of tobacco results in nitrogen oxides upon combustiori. These oxides can inhibit the formation of carcinogenic hydrocarbons under formation of nitroalkanes, nitrobenzenes, and other still un- identified components. Future Plans: To conduct detailed chemical studies on the inhibition of the pyrosynthesis of tumor initiators and tumor promoters in tobacco smoke; and bioassays on mouse skin of the mainstream smoke of cigarettes with modified tobacco. Project Dates: January 1961-1975. Source of Financial Support: American Health Foundation; USDA,ARS,CRD (12-14-100-10238 [381). References: (1) Hoffmann, D. and Rathkamp, G. "Chemical Studies on Tobacco Smoke. III. Primary and Secondary Nitroalkanes in Cigarette Smoke." Beitrage zur Tabakforschung 4(3):124-134, February 1968. (2) Hoffmann, D. and Wynder, E. L. `°The Reduction of the Tumorigenicity of Cigarette Smoke Condensate by Addition of Sodium Nitrate to Tobacco." Cancer Research 27:172-174, January 1967. (3) Wynder, E. L. and Hoffmann, D. "Present Status of Laboratory Studies on Tobacco Carcinogenesis." Acta Pathologica et Microbiologica Scandinavica 52(2):119-132, 1961. (4) Wynder, E. L. and Hoffmann, D. "Reduction of Tumorigenicity of Cigarette Smoke: An Experimental Approach." Journal of the American Medical Association 192:88-94, April 12, 1965. 6

10. 10. PrincipalInvestigators: E. L. Wynder and D. Hoffmann. •7 for the Carcinogenic and Tumor-promoting Activity of Cigarette Smoke ~ ject Tit e: -Bioassays f Objectfve:` To develop a time-saving standard method for the testing of tobacco "tar" and its fr tion$, and s.ubfractions for carcinogenicity and tumor-promoting activity; analyze "tars" and f~~ ;.:,, fr~ctio,ns for tumor. initiators and tumor promoters; and identify tumor promoters in neutral and a 'c~ic: fr~ctioiis, of .tobacco "tar." cf~4~.._,,.__. Nletfiods or` Approach: Tobacco "tars" and fractions are applied on the backs of ICR female mice ir~jX~riou~ .c~oses,. cycles, and frequencies for carcinogenicity and on mouse skin initiated with va~io,us doses ~of DMBA for tumor-promoting activity. Chemical analysis for tumorigenic agents is ._.. p~~£cl,rmed•,b-y chrorriatographic methods. evsults Tto Date.`• Tuiriorigenic responses in mouse skin can be accelerated by changes in dose and feq~uency of ;the_"tar',' application. The neutral and acidic fractions contain tumor promoters such a~~ .s .. IatBe plienols,, uonvolatile fatty acids, and alkylating agents- ~~~':..;: . ~ture`Pldns''To establish and define in detail an accelerated method for testing tobacco "tars" an r.utt~to £u}ther, identif.yy tumor promoters. : _ •.: ._- .. _.._ -. Project Date's:`January 1960=1975. ource o Financfal Support: Sloan-Kettering Institute for Cancer Research (until December 31, 1~69), HEW; I'HS, NIH, NCI_(CA-08748); ACS (E-231). ;~`:,.~_::.'.; .'.- . Re}'ererices: 1),W nder, E. L. and Hoffmann, D. "A Study of Tobacco Carcinogenesis. VIII. The Role of f.-.:~'.. • 1t~e~AGidic;Fractions as Promoters." Cancer 14(6):1306-1315, November-December 1961. W}~,nder,. E.*L, and Hoffmann, D. "A Study of Tobacco Carcinogenesis. X. Tumor Promoting 6 fAcfitnty ` Cancer 24(2):289-301, August 1969. 11. ll. AMERICAN HEALTH FOUNDATION Health Research Laboratory 180 East End Avenue New York, New York 10028 ANNA STATE HOSPITAL Behavior Research Laboratory - 1000 North Main Street Anna, Illinois 62906 PrincipalInvestigators: N. H. Azrin and J. Powell. , Objectivi 'e': 1fio~sdeferrmine' whether the behavioral engineering approach (specifically, use of an av~b&iye shock`technique or a conditioning apparatus) effectively helps reduce cigarette smoking. ~`'•,r.••:: .- M'etfiods or fI pproach: In one study, a special cigarette case that delivered aversive shock when opened was devised, and used with 20 male cigarette smoker volunteers. Consecutive procedural sfeps:included the subject's self-recording of amount of cigarettes smoked; subject's reading of lierature on .possible health hazards of smoking; wearing of the apparatus without shock punish- ent;,shock.;punishment for cigarette case opening and subsequent increases in shock intensity; ~,::., aI riall}i, withdrawal of shock punishment. In a second study, a cigarette case that automatically 1o,c,ked shut'for a period of time (ranging from 6 minutes to 65 minutes) after a cigarette was ~~tl: :..... , .. ..... .- l~~:i 7