DNA strand breaks and mutations caused by penbutolol, a beta blocker.
Sixteen beta-adrenergic receptor blockers were screened for their mutagenic potential using Salmonella typhimurium strains TA98 and TA100. All except penbutolol were found to be nonmutagenic. Penbutolol was cytotoxic to human fibroblasts and Chinese hamster V79 cells. These effects could be due to its ability to induce DNA-strand breaks detected by hydroxyapatite chromatography, which remained unrepaired within 1 h of incubation. Under the same conditions strand-breaking activity of propranolol, timolol and indenolol could not be detected. Three potential impurities of penbutolol were ineffective in causing DNA-strand breakage and one metabolite of this drug was found to be nonmutagenic.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects*; D010394:Penbutolol / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D010394:Penbutolol