MOLECULAR EPIDEMIOLOGY OF LUNG-CANCER AND THE MODULATION OF MARKERS OF CHRONIC CARCINOGEN EXPOSURE BY CHEMOPREVENTIVE AGENTS

Chronic inhalation exposure to environmental carcinogens such as polyc yclic aromatic hydrocarbons (PAHs), cigarette smoke, 4-aminobiphenyl ( 4-ABP), ethylene oxide, and styrene is associated with elevations in b iomarkers such as DNA adducts, protein adducts, sister chromatid excha nges (SCEs), chromosomal aberrations, gene mutation, and/or oncogene a ctivation. These biomarkers indicate an increased cancer risk for the exposed population, although quantitative estimates cannot be made wit h certainty. There is convincing epidemiological evidence that the ant ioxidant and free radical-scavenging vitamins C and E and beta-caroten e (beta-C) protect against cancer of the lung and other epithelial tis sues, with somewhat weaker evidence for retinol. Experimental studies demonstrate that these micronutrients are capable of blocking or reduc ing tumor formation caused by diverse carcinogens. A variety of mechan isms appear to be involved, including suppression of carcinogen activa tion, enhancement of carcinogen detoxification, induction of cellular differentiation, inhibition of mutagenesis, enhancement of immunologic function, and/or reduction of the formation of carcinogen-DNA adducts , SCEs, micronuclei, and other markers of genotoxic damage. Therefore, we have recently investigated the possible modifying effect of serum vitamins C and E, beta-C, and retinol on a number of such biomarkers i n a case-control study of lung cancer, and in a cross-sectional study of heavy smokers. Preliminary results indicate an inhibitory effect of certain vitamins on DNA adduct formation. A significant number of hum an intervention trials are ongoing involving these vitamins. It appear s that biomarkers can provide useful intermediate endpoints for assess ment of both the mechanisms and the efficacy of chemopreventive agents . (C) 1993 Wiley-Liss, Inc.