Vanadyl sulfate can differentially damage DNA in human lymphocytes and HeLa cells.
Using the comet assay, we showed that vanadyl sulfate induced DNA damage in human normal lymphocytes and in HeLa cells. Vanadyl at 0.5 and 1 mM produced DNA single- and double-strand breaks (SSBs and DSBs) in lymphocytes, whereas in HeLa cells we observed only SSBs. Post-treatment of vanadyl-damaged DNA from lymphocytes with formamidopyrimidine-DNA glycosylase (Fpg), an enzyme recognizing oxidized purines, gave rise to a significant increase in the extent of DNA damage. A similar effect was observed in HeLa cells, but, using endonuclease III, we also detected oxidized pyrimidines in DNA of these cells. There were no differences in the extent of DNA damage in the lymphocytes and HeLa cells in the pH >13 and pH 12.1 conditions of the comet assay, which indicates that strand breaks, and not alkali-labile sites, contributed to the measured DNA damage. Study of DNA repair, determined in the comet assay as an ability of cells to decrease of DNA damage, revealed that HeLa cells retained the ability to repair vanadyl-damaged DNA induced at a ten-fold higher concentration than that in lymphocytes. Incubation of the cells with nitrone spin traps DMPO, POBN and PBN decreased the extent of DNA damage, which might follow from the production of free radicals by vanadyl sulfate. The presence of vitamins A, C or E caused an increase of DNA damage in HeLa cells whereas in lymphocytes such an increase was observed only for vitamin C. Our data indicate that vanadyl sulfate can be genotoxic for normal and cancer cells. It seems to have a higher genotoxic potential for cancer cells than for normal lymphocytes. Vitamins A, C and E can increase this potential.
D001205:Ascorbic Acid / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D043382:DNA-Formamidopyrimidine Glycosylase / Q000494:pharmacology; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D029968:Escherichia coli Proteins / Q000494:pharmacology; D006367:HeLa Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology; D009153:Mutagens / Q000633:toxicity*; D019097:Spin Trapping; D017968:Vanadium Compounds / Q000633:toxicity*
D004338:Drug Combinations; D029968:Escherichia coli Proteins; D007004:Hypoglycemic Agents; D009153:Mutagens; D017968:Vanadium Compounds; C034028:vanadyl sulfate; D004247:DNA; D043224:Deoxyribonuclease (Pyrimidine Dimer); C106403:NTH protein, E coli; D043382:DNA-Formamidopyrimidine Glycosylase; D001205:Ascorbic Acid