Potentiation of dimethylnitrosamine genotoxicity in rat hepatocytes isolated following ethanol treatment in vivo |
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| Authors: | Michael J. Olson Joel G. Pounds Daniel A. Casciano |
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| Affiliation: | 1. Division of Interdisciplinary Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 U.S.A.;2. Department of Health and Human Services, Food and Drug Administration, National Center for Toxicological Research, Jefferson, AR 72079 U.S.A. |
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| 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. |
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| Keywords: | Unscheduled DNA synthesis Dimethylnitrosamine Cultured hepatocytes Ethanol treatment |
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