title: Potentiation of dimethylnitrosamine genotoxicity in rat hepatocytes isolated following ethanol treatment in vivo.
abstract: Unscheduled DNA synthesis (UDS), following exposure to dimethylnitrosamine (DMN), was potentiated in cultured hepatocytes isolated following treatment of rats for 14 or 28 days with 20% ethanol/5% sucrose solution. Ethanol treatment was associated with increased UDS, a concomitant increase in hepatic microsomal protein concentration and DMN N-demethylase activity. Increased aniline hydroxylase activity of hepatic microsomes from ethanol-treated rats preceded the measured increase in microsomal protein content or DMN metabolism. The increase in metabolism of DMN in vitro and potentiation of DMN-induced UDS associated with ethanol treatment may contribute to a synergistic effect of ethanol on DMN hepatotoxicity and carcinogenicity. In contrast, ethanol pretreatment did not increase the cytotoxicity of DMN as characterized by enzyme release.
mesh_terms: D000632:Aminopyrine / Q000378:metabolism; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D004260:DNA Repair / Q000187:drug effects; D003640:Dealkylation; D004128:Dimethylnitrosamine / Q000378:metabolism / Q000633:toxicity*; D004357:Drug Synergism; D000431:Ethanol / Q000633:toxicity*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009153:Mutagens; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000814:Aniline Compounds; D009153:Mutagens; D000632:Aminopyrine; D000431:Ethanol; D007770:L-Lactate Dehydrogenase; D004128:Dimethylnitrosamine; C023650:aniline