A comparative study of genotoxic effects of anti-topoisomerase II drugs ICRF-193 and bufalin in Chinese hamster ovary cells.
With the ultimate purpose of testing the existence of possible differences in the effectiveness of the topoisomerase II catalytic inhibitor ICRF-193 (a bisdioxopiperazine) and the enzyme suppressor bufalin (a bufadienolide from toad venom) we have carried out a series of experiments aimed at inducing cytotoxicity as well as DNA and chromosome damage in transformed CHO cells. In order to assess any possible influence of DNA repair capacity of the treated cells on the final outcome, we have made use of the repair-defective CHO mutant EM9, which shows a defect in DNA single- and double-strand breaks repair for comparison with its repair-proficient parental line AA8. Our results seem to indicate that, while both ICRF-193 and bufalin suppress cell growth and result in a clear inhibition of topoisomerase II catalytic activity, only ICRF-193 has been shown as able to induce both chromosome and DNA damage, with a more pronounced effect in the CHO mutant EM9 than in the repair-proficient line AA8.
Pastor
Nuria
N
Department of Cellular Biology, Faculty of Biology, University of Seville, Avda. Reina Mercedes No. 6, 41012, Seville, Spain.
Domínguez
Inmaculada
I
Mateos
Santiago
S
Cortés
Felipe
F
D000818:Animals; D002018:Bufanolides / Q000633:toxicity*; D016466:CHO Cells / Q000187:drug effects*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D002875:Chromosomes / Q000187:drug effects*; D020552:Comet Assay; D006224:Cricetinae; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000633:toxicity*; D009152:Mutagenicity Tests; D009154:Mutation; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D059005:Topoisomerase II Inhibitors
D002018:Bufanolides; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D000254:Sodium-Potassium-Exchanging ATPase; C022777:bufalin