title: Mutagenicity and DNA-excision repair induced by isoniazid after metabolic activation by isolated human and rat hepatocytes.
abstract: The mutagenic potency of isoniazid (INH) (a widely used antitubercular drug) towards Salmonella typhimurium strain hisG46 was studied in the Salmonella/hepatocyte suspension-assay, comprising isolated human or rat hepatocytes as metabolic system. The potency of INH to induce DNA-excision repair in these hepatocytes was also measured. With rat hepatocytes, INH appeared to be only weakly mutagenic and did not induce significant increases in hepatocellular DNA-excision repair. With isolated hepatocytes of two human subjects, INH appeared also only weakly mutagenic. However, with hepatocytes of two other human subjects, INH was found to be highly mutagenic. Comparable results were obtained for the induction of hepatocellular DNA-excision repair.
mesh_terms: D000107:Acetylation; D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D007538:Isoniazid / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens; D051381:Rats; D012486:Salmonella typhimurium / Q000235:genetics
chemical_list: D009153:Mutagens; D003577:Cytochrome P-450 Enzyme System; D007538:Isoniazid