Effects of vitamins on chromium(VI)-induced damage.
The effects of vitamin E and vitamin B2 on DNA damage and cellular reduction of chromium(VI) were investigated using Chinese hamster V-79 cells. Pretreatment with alpha-tocopherol succinate (vitamin E) resulted in a decrease of DNA single-strand breaks produced by Na2CrO4, while similar treatment with riboflavin (vitamin B2) enhanced levels of DNA breaks. In contrast, levels of DNA-protein crosslinks induced by Na2CrO4 were unaffected by these vitamins. Electron spin resonance (ESR) studies showed that incubation of cells with Na2CrO4 resulted in the formation of both chromium(V) and chromium(III) complexes, and cellular pretreatment with vitamin E reduced the level of the chromium(V) complex, whereas pretreatment with vitamin B2 enhanced the level of this intermediate. However, the levels of chromium(III) were unchanged by these vitamins. The uptake of chromate was not affected by vitamin E or vitamin B2, nor were the levels of glutathione or glutathione reductase activity, which are both capable of reducing chromate. ESR studies demonstrated that a chromium(V) species was formed by the reaction of Na2CrO4 with vitamin B2 and that vitamin B2 enhanced the formation of hydroxyl radicals during the reaction of Na2CrO4 and hydrogen peroxide. Treatment cells with Na2CrO4 resulted in a decrease of glutathione reductase activity, and pretreatment with vitamin E restored the enzyme activity suppressed by this metal. However, pretreatment with vitamin B2 enhanced the inhibition of this enzyme by Na2CrO4. Using a colony-forming assay, pretreatment with vitamin E dramatically decreased the cytotoxicity of Na2CrO4, while pretreatment with vitamin B2 was found to result in only a decrease of cell lethality of this metal.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medical Biochemistry, Kurume University School of Medicine, Japan.
M
M
Sugiyama
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002857:Chromium / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D006224:Cricetinae; D004249:DNA Damage; D004347:Drug Interactions; D005609:Free Radicals; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction; D012256:Riboflavin / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology*
D005609:Free Radicals; D002857:Chromium; D014810:Vitamin E; D005980:Glutathione Reductase; D012256:Riboflavin