Protective action of vitamin C against DNA damage induced by selenium-cisplatin conjugate.
Genotoxicity of anticancer drugs is of a special interest due to the risk of inducing secondary malignancies. Vitamin C (ascorbic acid) is a recognized antioxidant and, since human diet can be easily supplemented with vitamin C, it seems reasonable to check whether it can protect against DNA-damaging effects of antitumor drugs. In the present work the ability of vitamin C to modulate cytotoxic and genotoxic effects of a cisplatin analog, conjugate (NH3)2Pt(SeO3), in terms of cell viability, DNA damage and repair in human lymphocytes was examined using the trypan blue exclusion test and the alkaline comet assay, respectively. The conjugate evoked a concentration-dependent decrease in the cell viability, reaching nearly 50% at 250 microM. (NH3)2Pt(SeO3) at 1, 10 and 30 microM caused DNA strand breaks, measured as the increase in the comet tail moment of the lymphocytes. The treated cells were able to recover within a 30-min incubation in a drug-free medium at 37 degrees C. Vitamin C at 10 and 50 microM diminished the extent of DNA damage evoked by (NH3)2Pt(SeO3) but had no effect on the kinetics of DNA repair. The vitamin did not directly inactivate the conjugate. Lymphocytes treated with endonuclease III, which recognises oxidised pyrimidines, displayed a greater tail moment than those untreated with the enzyme, suggesting that the damages induced by the drug have, at least in part, an oxidative origin. Vitamin C can be considered a potential protective agent against side effects of antitumor drugs, but further research with both normal and cancer cells are needed to clarify this point.
Błasiak
J
J
Department of Molecular Genetics, University of Lódź, Poland. januszb@taxus.biol.uni.lodz.pl
Kowalik
J
J
D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology*; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004305:Dose-Response Relationship, Drug; D004706:Endodeoxyribonucleases / Q000494:pharmacology; D029968:Escherichia coli Proteins; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D011487:Protein Conformation; D012643:Selenium / Q000494:pharmacology*; D013997:Time Factors
D000970:Antineoplastic Agents; D000975:Antioxidants; D029968:Escherichia coli Proteins; D004706:Endodeoxyribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer); C106403:NTH protein, E coli; D012643:Selenium; D001205:Ascorbic Acid; D002945:Cisplatin