Scientific challenges in environmental carcinogenesis.

We reviewed three of our ongoing interdisciplinary studies in environmental carcinogenesis. In the case of snuff dipping and cancer of the oral cavity our data strongly support the epidemiological findings. Bioassays have demonstrated that oral snuff induces cancer of the oral cavity of rats, that the major carcinogens in snuff are NNN and NNK and that swabbing of the mouth with a solution containing NNN and NNK induces tumors in rats at the site of application. Biochemical studies are currently underway to provide further documentation that oral snuff is a carcinogen in humans. The major leukemogenic agent in cigarette smoke is benzene. Biomarker studies with t,t-MA, a urinary metabolite of benzene, have shown significantly higher uptake of benzene by smokers than by nonsmokers and benzene uptake by smokers of the order found in the urine of workers with low occupational exposure to benzene. These studies are being continued. Laboratory studies have supported the concept that smokers of low-yield cigarettes are more likely to have higher risk for lung adenocarcinoma than smokers of high-yield cigarettes who were more likely to develop squamous cell carcinoma. Smokers of low-yield cigarettes smoke more intensely and inhale more deeply to satisfy a need for nicotine. These changes in smoking patterns lead to relatively greater exposure of the bronchioalveolar regions and smaller bronchi to lung carcinogens, some of which have organ specificity and may well be responsible for induction of adenoma or adenocarcinoma of the peripheral lung. Biomarker studies are in progress to verify this hypothesis.