The potent hepatocarcinogen methapyrilene does not form DNA adducts in livers of Fischer 344 rats.
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.
Casciano
D A
DA
National Center for Toxicological Research, Division of Genetic Toxicology, Jefferson, AR 72079.
Shaddock
J G
JG
Talaska
G
G
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
D000631:Aminopyridines; D002273:Carcinogens; D004247:DNA; D008701:Methapyrilene