The in vitro study of influence of antioxidant enzymes level and repair capacity on cytotoxic bleomycin activity in human and mouse cells.
Bleomycin, an antitumour antibiotic was used to study the possible relationship between DNA single strand breaks repair capacity, antioxidant enzymes level and cytotoxic activity of the drug in mouse cells: AKR and BALB/c and in human cells: CRL 2088 and CRL 1307 (xeroderma pigmentosum). The BALB/c and CRL 1307 cells were used because of having defects in DNA repair capacity. A positive correlation was shown to exist between IC50 values and repair ability which suggested that DNA single strand breaks could be responsible for cytotoxic effects of bleomycin in human and mouse cells. Also antioxidant enzymes level have occurred as, at least partly, participating in bleomycin cytotoxic efficiency. About 10-fold higher resistance of AKR cells to bleomycin in comparison with the other cells, as appeared here, did not exhibit the straight correlation with antioxidant status of the cells. It prompts participation of the other mechanism in bleomycin cytotoxic action than that based on free radical generation. Also drug distribution and metabolism should be considered as a possible factor needed in bleomycin efficacy evaluation.
Gruber
B M
BM
Drug Institute, Warsaw, Poland.
Anuszewska
E L
EL
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000187:drug effects; D006801:Humans; D051379:Mice; D013482:Superoxide Dismutase / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D001761:Bleomycin; D002374:Catalase; D013482:Superoxide Dismutase