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Anticarcinogenous Substances in Tobacco Smoke V. Fetvadiev, A. Sanev, St. Lazou, L. Pileva a Tobacco Research Institute, Plovdiv, Bulgaria Study of tobacco smoke as a cause or promoter of lung cancer shows that tobacco smoke contains typical carcinogenous substances such as polycyclic hydrocarbons, especially benzo(a)pyrene. Hoiko and Lain reported that: 3,4,8,9-dibenzpyrene; 1,2,3,4-dibenzpyrene 3,4 9,10-dibenzpyrene; 3-methyl-l,2-benzanthracene; 1,12-benzperylene; 5,6-cyclo- pentano-1,2«benzanthracene, if used in the absence of other compounds, are true carcinogenous substances. But so far nothing has been done about the relation between amount of benz(a)pyrene and other polycyclic hydrocarbons in tobacco smoke in connection with lung cancer. Research data clearly demonstrate that Oriental and air-cured tobacco, regard- less of amount of benz(a)pyrene, are not potentially as dangerous as fluepcured tobacco. Also, it is a known fact that tobacco smoke from cigarettes contains much more polycyclic hydrocarbons, particularly carcinogenic ones, than smoke of the same tobacco used in pipes. Pipe smoking is less dangerous than cigarettes. Content of carcinogenous substances in tobacco smoke and potential danger .,.of lung cancer depends on various circumstancial factors such as: (1) Degree of adsorbability of carcinogenic compounds from other particles in tobacco smoke; (2) Process of separation of polycyclic hydrocarbons -from smoke, depending on their size; (3) Protective ability of human organism, especially activity of (merzatelnogo) epithelium in respiratory system; (4) -Presence in tobacco smoke, compounds of importance in human metabolism; (5) Anticarcinogenous substances which are found in tobacco smoke. The most important from all factors, of course, are these anticarcinogenic compounds. The discovery of anticarcinogenic compounds not only provides the possibility of producing less harmful tobacco (cultivate proper tobacco types and using proper methods of curing) but also suggests that smoking tobacco with high level of anticarcinogenous substances may give protection against the carcinogenic compounds which occur in air. Depending of their action, anticarcinogenic substances could be divided on .two groups. I. Compounds which displace carcinogenous substances from organisms and therefore prevent development of tumors; II. Compounds which attack tumorous tissues and therefore inhibit growth or kill it. The action of Group I might be explained by the known fact that physiod logically active compounds could be inactivated by compounds close to them either by chemical structure of their derivatives. In other words, when the two compounds are simultaneously introduced, one will be absorbed and the other inhibited. As an example, if weak carcinogenic substances

2 or noncarcinogenic compounds, but by structure are close to strong carcinogens, get into an affected cell, the strong carcinogenous compound will be inhibited and as a result tumors will decrease or demolish (Kotin, Shainer, Kryabtrii). Dose of Inhibitor Carcinoa " genic in mg to carcinogen at ratio 15:1 completely protect organism from development of any tumor. Benz(a)anthracene dihydrobenz(ah) anthracene Dose of Inhibitor Ratio Inhibitor: Carcinogen % of Inhibition Tumors w inhibitor/ control 5000 250:1 70 11/28 450 15:1 100 0/7 Carcinogenous compound, dibenz(ah)anthracacene and its derivatives of different dosage were subcutaneously injected in mice. As we see, carcinogenous derivatives demonstrated different ability of inhibiting tumor growth. For instance: phenontrene to carcinogen at ration 48:1 decrease danager of cancer formation by 60%, but dihydrobenz(ah)anthracene -carcinogenous, others anticarcinogenous. Anti-carcinogenic substances in tobacco smoke are: benz(e)pyrene, anthracene, pyrene, perylene and others. Tobacco smoke condensate contains polycyclic hydrocarbons, some of them First quantitative analysis of anticarcinogenic and carcinogenic substances in tobacco smoke shows that quantity of anticarcinogenic compounds are much higher than carcinogenic at the ratio 10:1 and 150:1. The high proportion of anticarcinogenous substances occur in air-cured types and Oriental tobacco, in which processes of yellowing, drying and fermentation are natura- ily slow and complete. This is probably why considerably less cases of lung cancer occurred in countries where Oriental or air-cured tobacco is used, and on the other hand much more lung cancer cases in the countries using flue-cured tobacco. Flue-curing process differs with an air-curing process in that the

3 yellowing, drying and fermentation are not complete in the former case. Table 2 shows types of tobacco and cases of cancer in different countries. Country Type of tobacco used Cancer of respiratory system in cigarettes 100.000 people Men Women England Flue-cured 90.9 15.5 U. S. A. Flue-cured, air-cured, Oriental 39.9 6.9 U.S.S.R. Oriental, semi-Oriental 31.4 5.4 Summary from Original Paper Tobacco smoke contains both carcinogenous and anticarcinogenous substances. The potential danger which the smoke condensate represents in respect to causing of lung cancer does not account for the absolute contents of ?.carcinogenous substances, but it depends rather on the ratio between the -carcinogenous and anticarcinogenous components in it. Anticarcinogenous -,substances in significant quantities found in the tobacco smoke are: anthracene, pyrene, benz(e)pyrene, benzathracene and perylene. Anticarcinogenous substances are found in larger quantities and the ratio anticarcinogenous:carcinogenous is higher in tobacco which undergoes the processes of yellowing, curing and fermentation in higher degree and in deeper way. Such are the tobaccos: air cured, oriental and semiQoriental types. By increasing the amount of anticarcinogenous substances in tobaccq smoke add at the same time reducing the carcinogenous ones by means of selection work, curing, fermentation and manufacturing, there lies a possibility not only of eliminating a potential danger which the tobacco smoke presents as .causal factor in inducing of lung cancer in smokers of cigarettes, butt also of safeguarding them against the carcinogenous substances which are found in the air of big, industrial cities.