Studies in tobacco carcinogenesis

Abstract

The vapour phase of freshly generated cigarette mainstream smoke, of sidestream smoke and of environmental tobacco smoke was analysed for such tumorigenic agents as benzene, 1,3-butadiene and acrolein with a newly developed, highly sensitive gas chromatography-mass selective detection method. The major carcinogen in tobacco smoke, catechol, was studied in regard to its specific action on the metabolism of benzo[a]pyrene in mouse lung and mouse skin. The major tobacco-specific carcinogens in tobacco and its smoke are the nicotine-derived N-nitrosamines, N'-nitrosonornicotine and 4-(nitroso-methylamino)-1-(3-pyridyl)-1-butanone. A third nitrosamine that can be formed in vitro by nitrosation of nicotine is 1-(nitrosomethylamino)-1-(3-pyridyl)butylaldehyde. This aldehyde is not present in tobacco products, but its noncarcinogenic oxidation product, 4-(nitrosomethylamino)-1-(3-pyridyl)butyric acid, was found in tobacco and can be formed from the major nicotine metabolite, cotinine. It is also likely that this acid can be formed by endogenous reactions.