title: Alcohol-related cancer risk: a toxicokinetic hypothesis.
abstract: Consumption of alcoholic beverages is an accepted social custom world-wide. This makes its involvement in events contributing to human cancer risk very important. Although it is neither tumorigenic nor genotoxic in animals, ethanol can potentiate the carcinogenic risk associated with certain environmentally present agents. The reasons for such a synergistic 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 this hypothesis, demonstrating increased exposure of posthepatic organs to nitrosamines when given in combination with ethanol, followed by enhancement of DNA adduct formation and, at least in rodents, of tumor development. In addition, ethanol may induce enzymes responsible for carcinogen activation, including hepatic cytochrome P450 2E1 in rodents and humans, and in lung, kidney, and brain in rodents. Studies have also shown that these effects can extend to the next generation via maternal and in utero fetal exposure. What impact such ethanol-induced modulations have on tumorigenesis during childhood and later stages of life needs to be investigated further.
authors.affiliation: Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Anderson
authors.forename: S K
authors.initials: SK
authors.lastname: Chhabra
authors.forename: P V
authors.initials: PV
authors.lastname: Nerurkar
authors.forename: V L
authors.initials: VL
authors.lastname: Souliotis
authors.forename: S A
authors.initials: SA
authors.lastname: Kyrtopoulos
mesh_terms: D000818:Animals; D000431:Ethanol / Q000009:adverse effects*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology*; D012307:Risk Factors
chemical_list: D000431:Ethanol