Studies on the mutagenic activity of hydralazine and dihydralazine in Salmonella typhimurium strains differing in expression of antioxidant genes.
The mutagenic activity of two antihypertensive drugs, hydralazine and dihydralazine was investigated in oxyR- proficient (TA104) and -deficient (TA4125) Salmonella typhimurium strains showing different ability to induce proteins involved in protection of the cells against oxidative damage. The results of the Ames test demonstrated that dihydralazine, in contrast to hydralazine, was mutagenic for oxyR- strain at concentrations that were nonmutagenic for oxyR+ strain. The scavenger of superoxide anion, superoxide dismutase decreased in both strains the number of revertants induced by dihydralazine but not by hydralazine. The results may suggest that active oxygen species generated by dihydralazine contribute to its mutagenicity.
Chłopkiewicz
B
B
Drug Institute, Warsaw, Poland. chlopkie@il.waw.pl
D000959:Antihypertensive Agents / Q000633:toxicity*; D004249:DNA Damage; D004268:DNA-Binding Proteins; D004078:Dihydralazine / Q000633:toxicity*; D006830:Hydralazine / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*; D018384:Oxidative Stress; D012097:Repressor Proteins / Q000235:genetics*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*
D000959:Antihypertensive Agents; D004268:DNA-Binding Proteins; D009153:Mutagens; D012097:Repressor Proteins; D014157:Transcription Factors; D013481:Superoxides; D006830:Hydralazine; D004078:Dihydralazine