Endogenous Formation of Nitrosamines and Oxidative DNA-Damaging Agents in Tobacco Users
Smokeless tobacco, most widely used in the form of chewing of betel quid (BQ) with tobacco, was shown to particularly enhance endogenous nitrosation in the oral cavity, a site where chewing habits are causally associated with cancer. Both in tobacco smoke and smokeless tobacco, carcinogenic N-nitroso compounds are implicated as DNA-damaging agents in cancers of the aerodigestive tract and the pancreas. When nicotine was given by infusion to volunteers, less than 1% of the alkaloid was converted into nornicotine via oxidative demethylation. Evidence is also accumulating for the endogenous synthesis of nitrosamines from nitric oxide-mediated reactions that are generated during inflammatory processes via nitric oxide synthase. Further evidence for the possible occurrence of endogenous formation of nitrosamines was obtained from in vitro studies by nitrosation of alkaloids present in tobacco and BQ. Epidemiological studies suggested that tobacco and other BQ ingredients could act synergistically in the causation of oral cancer.