Potential inhibitors of tobacco carcinogenesis.

Tobacco smoking is causally associated with cancer of the lung, upper aerodigestive tract, pancreas, renal pelvis and urinary bladder. Tobacco chewers and especially snuff dippers face an increased risk for cancer of the oral cavity and pharynx. Although cessation of the tobacco habits is the only sure way to avoid an increased risk of tobacco-related cancers, certain modified products should be available to lower the incidence rates for cancer among those tobacco chewers and smokers who are unable to give up their tobacco habits. The modified cigarette has been the first approach toward the reduction of cancer risk. In the case of cancer of the lung, the long-term smoker of low-yield filter cigarettes has a risk reduction of 30-50% over that of the smoker of nonfilter cigarettes; however, the risk of filter cigarette smokers for cancer of the lung and cancer at other sites is still many times higher than that of the nonsmoker. A second modality is the application of natural or synthetic chemopreventive agents. Clinical studies with tobacco users have been primarily limited to the application of beta-carotene and retinoids. Although the data appear encouraging in respect to reducing early lesions in the oral cavity of tobacco chewers and smokers and in respect to second primaries in smokers, the benefits of beta-carotene and retinoids are gradually reversed upon withholding these micronutrients. It is understandable that activities in respect to chemopreventive agents in clinical trials on smokers are limited, since cessation of smoking alone leads within only a few years to a significant reduction of the cancer risk. Another reason for the limited interest in clinical trials on smokers may relate to the lack of laboratory data on the actual effects of chemopreventive agents in animals induced with tobacco-specific carcinogens. However, during the last few years, a number of natural or synthetic chemopreventive agents in animals induced with tobacco-specific carcinogens. However, during the last few years, a number of natural or synthetic chemopreventive agents have been tested in mice and rats which were treated with carcinogenic, tobacco-specific N-nitrosamines (TSNA). The results appear most encouraging in respect to lung tumor reduction. It is hoped that this type of research will gain in interest. Human data suggest that the fat content of the diet influences the cancer risk of smokers.(ABSTRACT TRUNCATED AT 400 WORDS)