Influence of metabolic activation on the induction of micronuclei by antihypertensive drugs in L929 cells.
The influence of metabolic activation on the genotoxic activity of the antihypertensive drugs hydralazine and dihydralazine was investigated. An in vitro micronucleus test for estimating the genotoxic activity of these drugs was used. The results obtained indicated that hydralazine and dihydralazine induce micronuclei formation in L929 cells. When L929 cell cultures were treated with drugs together with liver membrane fraction (S9 fraction) from polychlorinated biphenyl (Aroclor 1254) induced rat liver, the number of micronucleated cells decrease, however, almost to the level found in control cultures. The experiments with modified S9 mix allow the conclusion that the antioxidant enzymes catalase and superoxide dismutase present in S9 liver fraction play a role in the protection of cells from the genotoxic action of hydralazine and dihydralazine.
Chłopkiewicz
B
B
Drug Institute, Warsaw, Poland. chlopkie@il.waw.pl
D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism / Q000633:toxicity*; D001140:Aroclors / Q000494:pharmacology; D001711:Biotransformation; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D003238:Connective Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004078:Dihydralazine / Q000378:metabolism / Q000633:toxicity*; D004789:Enzyme Activation; D006358:Hot Temperature; D006830:Hydralazine / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism
D000959:Antihypertensive Agents; D001140:Aroclors; D009153:Mutagens; D006830:Hydralazine; D002374:Catalase; D013482:Superoxide Dismutase; D004078:Dihydralazine