ALCOHOL-RELATED CANCER RISK - A TOXICOKINETIC HYPOTHESIS

Consumption of alcoholic beverages is an accepted social custom world- wide. This makes its involvement in events contributing to human cance r risk very important. Although it is neither tumorigenic nor genotoxi c in animals, ethanol can potentiate the carcinogenic risk associated with certain environmentally present agents. The reasons for such a sy nergistic action are speculative, but among theories postulated may be ethanol's ability to modify the toxicokinetics/dynamics of carcinogen metabolism. Experiments conducted with rodents and primates support t his hypothesis, demonstrating increased exposure of posthepatic organs to nitrosamines when given in combination with ethanol, followed by e nhancement of DNA adduct formation and, at least in rodents, of tumor development. In addition, ethanol may induce enzymes responsible for c arcinogen activation, including hepatic cytochrome P450 2E1 in rodents and humans, and in lung, kidney, and brain in rodents. Studies have a lso shown that these effects can extend to the next generation via mat ernal and in utero fetal exposure. What impact such ethanol-induced mo dulations have on tumorigenesis during childhood and later stages of l ife needs to be investigated further.