title: Genotoxicity, toxicity, and carcinogenicity of the antihistamine methapyrilene.
abstract: The antihistamine methapyrilene hydrochloride (MP) has been shown to be a potent hepatocarcinogen in rats, but not in hamsters or guinea pigs. This finding is in contrast to the relative nongenotoxicity of this compound. MP has been evaluated for genotoxicity in a wide variety of short-term tests and has generally demonstrated little genotoxic activity. One exception to this is the mouse lymphoma L5178Y mutagenesis assay, in which MP produced a very significant increase in small colony mutants with concomitant chromosomal damage in these cells. MP also induced positive responses in several cell transformation assays. One potentially very significant effect of MP is that it induces a large increase in hepatic cell proliferation coupled with mitochondrial proliferation in the livers of treated animals. This effect is discussed as a possible mechanism of liver tumor induction in rats.
mesh_terms: D000631:Aminopyridines / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D002273:Carcinogens; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D008701:Methapyrilene / Q000633:toxicity*; D051379:Mice; D009154:Mutation / Q000187:drug effects; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects
chemical_list: D000631:Aminopyridines; D002273:Carcinogens; D008701:Methapyrilene