Smokeless tobacco and cancer

Epidemiological data have demonstrated that smokeless tobacco users face an increased risk of cancer of the oral cavity. Bioassays for carcinogenicity of chewing tobacco and snuff in laboratory animals have thus far been inconclusive. Chemical studies have shown that nicotine and other Nicotiana alkaloids give rise to tobacco-specific N-nitrosamines (TSNA). Some of these TSNA are strongly carcinogenic in mice, rats, and hamsters. TSNA in chewing tobacco and especially in snuff amount to several parts per million and exceed by at least two orders of magnitude the levels of carcinogenic nitrosamines in other consumer products. Metabolic activation of TSNA leads to unstable electrophiles which alkylate DNA bases in those organs in which the TSNA induce tumors. The biochemistry of tumor induction by TSNA is now being studied. At this time, adducts of TSNA metabolites with globin are being utilized as biological markers for the uptake of tobacco carcinogens, and new techniques for the bioassay of smokeless tobacco and snuff are being explored.