METABOLIC POLYMORPHISMS AND CARCINOGEN-DNA ADDUCT FORMATION IN HUMAN-POPULATIONS

Metabolic polymorphisms have long been recognized as important determi nants of carcinogen susceptibility and recent efforts have shown that interindividual differences in specific cytochromes P450, acetyltransf erases, sulfotransferases and glutathione S-transferases are often dis proportionately represented in epidemiological studies between cancer cases and controls. Concomitantly, biomonitoring of carcinogen-DNA add ucts in human tissues using immunochemical, (32)p-postlabelling, fluor escence, and mass spectrometric methods have recently provided direct evidence of human exposure to genotoxic aromatic and heterocyclic amin es, polycyclic hydrocarbons, alkylating agents, and endogenous product s. However, a combined approach is now needed in order to assess the r elevance of these findings to cancer etiology, to identify high-risk i ndividuals, and to provide better health monitoring, earlier diagnosis , and cancer prevention. Using this paradigm, results are presented th at implicate specific aromatic amines, heterocyclic amines, and polycy clic aromatic hydrocarbons in the etiology of human urinary bladder, c olon, and laryngeal cancers.