NICOTINE AND SOME CARCINOGENS IN SPECIAL REFERENCE TO THE HEPATIC DRUG-METABOLIZING ENZYMES

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In the past few years it has been found that various carcinogenic hydrocarbons (e.g. 3, 4-benzpyrene and 3-methylcholanthrene) and drugs (e.g. phenobarbital and aminopyrine) increase markedly the activity of the enzyme systems in liver microsomes which metabolize several foreign compounds (1). About 16 μg (average of 10 reports) of 3, 4benzpyrene has been reported to be contained in smoke of 1, 000 cigarettes (2), but studies on the relationship between nicotine and the carcinogens have not been done from the standpoint of drug metabolism. During the course of pharmacological investigations of nicotine in our laboratory (3-5), the effect of the carcinogens on nicotine metabolism and the converse, the effect of nicotine on the carcinogen metabolism were subjected to be investigated.<BR> Data presented in this paper indicates that 2-acetylaminofluorene, 3, 4-benzpyrene and 3-methylcholanthrene enhanced the activity of nicotine metabolizing enzyme and that nicotine also increased the activity of metabolizing enzymes toward 2-acetylaminofluorene and 3, 4-benzpyrene in rat liver microsomes.