The effects of α-tocopheryl succinate (Toc-suc), riboflavin (RF) and ascorbic acid (AsA) on chromate-caused DNA damage, enzyme inhibition and cellular reduction of chromium (VI) were investigated using Chinese hamster V-79 cells. Pretreatment with Toc-suc or AsA resulted in a decrease of DNA single strand breaks or alkali-labile sites produced by Na_2CrO_4, while similar pretreatment with RF enhanced levels of both DNA damages. In contrast, levels of DNA-protein crosslinks caused by Na_2CrO_4 were unaffected by Toc-suc or RF, but the levels were increased by AsA. Pretreatment with Toc-suc or AsA restored glutathione reductase activity suppressed by Na_2CrO_4, however, RF pretreatment enhanced the inhibition of this enzyme by this metal. Using a colony-forming assay, pretreatment with Toc-suc dramatically decreased the cytotoxicity of Na_2CrO_4, and similar treatment with RF was found to result in only a decrease of cell lethality of this metal, while the cytotoxicity of chromate was enhanced by AsA. The uptake of chromate was not affected by Toc-suc or RF, but increased by AsA pretreatment. Electron spin resonance (ESR) studies showed that pretreatment with Toc-suc or AsA reduced the level of chromium (V) complex in cells, whereas RF pretreatment enhanced the level of this intermediate. With respect to chromium (III), AsA pretreatment was found to increase, but Toc-suc or RF did not. These results indicate that vitamins are capable of altering the biological effects of carcinogenic chromium (VI) compounds, possibly through their abilities to modify levels of paramagnetic chromium in cells. the importance of the role of vitamins in chromium (VI)-induced carcinogenicity and toxicity is discussed.
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