title: The potent hepatocarcinogen methapyrilene does not form DNA adducts in livers of Fischer 344 rats.
abstract: The antihistamine methapyrilene hydrochloride has been shown to be a potent hepatocarcinogen in Fischer 344 rats. It has also been evaluated in a number of short-term in vitro genotoxicity assays resulting in conflicting reports. Short-term in vivo assays suggest that it may act as a promoter. We studied its ability to form DNA adducts in the target organ using the highly sensitive 32P-postlabeling technique. Methapyrilene failed to induce formation of DNA adducts in hepatocellular DNA at doses which induced S-phase DNA synthesis. These data suggest that methapyrilene does not induce the carcinogenesis process through a direct genotoxic mechanism.
authors.affiliation: National Center for Toxicological Research, Division of Genetic Toxicology, Jefferson, AR 72079.
authors.forename: D A
authors.initials: DA
authors.lastname: Casciano
authors.forename: J G
authors.initials: JG
authors.lastname: Shaddock
authors.forename: G
authors.initials: G
authors.lastname: Talaska
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D002273:Carcinogens; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D007399:Interphase; D008099:Liver / Q000187:drug effects; D008115:Liver Regeneration / Q000187:drug effects; D008701:Methapyrilene / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000631:Aminopyridines; D002273:Carcinogens; D004247:DNA; D008701:Methapyrilene