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Mechanisms of chemical carcinogenesis.

Despite the seemingly disparate endpoints, there are similarities between many drugs and chemical carcinogens when viewed from the basis of pharmacological or toxicological principles. Various biochemical reactions or metabolic pathways of chemical carcinogens are the same as those of other xenobiotics. Similar enzyme systems operate in both cases. Certain biochemical pathways, once assumed to be manifest only in carcinogens, have been discovered from some drugs, where some of the toxic side effects may be due to these metabolic transformations (1-4). Another possibility is that drugs can themselves be carcinogenic; this is more likely to hold for those employed in the chemotherapeutic treatment of neoplastic disease (5-7). Finally, there are several reports that drugs that contain secondary or tertiary amine structures may react with nitrite, formed endogenously, to yield nitrosamines, many of which are potent carcinogens in most species (8). Against this background, it should be recognized that just as one drug can influence the metabolism of another (9, 10), likewise the effects of carcinogens can often be altered by other chemical entities. These topics are mentioned in the following sections.