Studies on the mechanisms of an H2O2 adaptive dose on DNA damage in human neoplastic cells treated with adriamycin.
The possible influence of a hydrogen peroxide adaptive dose on DNA damage induced by adriamycin treatment in human melanoma cells, sensitive (ME18) and resistant (ME18/R) to adriamycin was investigated. In our earlier work, it was shown that the human melanoma resistant subline exhibited, in contrast to the parental cell line, the capacity to evoke an adaptive response provoked by low doses of hydrogen peroxide. This was observed as a diminished cytotoxic effect of adriamycin used at a toxic dose. The current work showed that an adaptive dose of hydrogen peroxide (2 microM) reduced DNA--single strand breaks, generated by a challenging dose of adriamycin in both, sensitive and resistant human melanoma cells. For better understanding of the adaptive response mechanism, exogenous free radical scavengers were used. In this study, it was shown that superoxide dismutase used at a concentration of 200 u/ml and mannitol at concentration of 100 mM modulated adriamycin--generated DNA--single strand breaks in parental melanoma cells. None of the exogenous scavengers, used in this study, influenced the cytotoxic effects of adriamycin either in sensitive or in resistant melanoma cells.
Gruber
B M
BM
Department of Vitamin Drugs, Drug Institute, 30/34 Chełmska Str., 00-725 Warsaw, Poland.
Anuszewska
E L
EL
D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D004317:Doxorubicin / Q000633:toxicity*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D016877:Oxidants; D004317:Doxorubicin; D006861:Hydrogen Peroxide