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: D A Casciano, J G Shaddock, G Talaska
• Journal: Mutation research (Mutat Res) Vol. 208 Issue 3-4 Pg. 129-35 (Jul 1988) ISSN: 0027-5107 [Print] Netherlands
• PMID: 3398863 (Publication Type: Journal Article)

Chemical References

• Aminopyridines
• Carcinogens
• DNA
• Methapyrilene

Topics

• Aminopyridines (pharmacology)
• Animals
• Carcinogens
• DNA (drug effects)
• DNA Damage
• DNA Repair
• DNA Replication
• Interphase
• Liver (drug effects)
• Liver Regeneration (drug effects)
• Methapyrilene (pharmacology)
• Rats
• Rats, Inbred F344