Comparative studies of tri- and hexavalent chromium cytotoxicity and their effects on oxidative state of Saccharomyces cerevisiae cells.

Chromium is a significant mutagen and carcinogen in environment. We compared the effects of tri- and hexavalent chromium on cytotoxicity and oxidative stress in yeast. Cell growth was inhibited by Cr(3+) or Cr(6+), and Cr(6+) significantly increased the lethal rate compared with Cr(3+). Both Cr(3+) and Cr(6+) can enter into the yeast cells. The percent of propidium iodide permeable cells treated with Cr(3+) is almost five times as that treated with the same concentration of Cr(6+). Levels of TBARS, O2 (-), and carbonyl protein were significantly increased in both Cr(6+)- and Cr(3+)-treated cells in a concentration- and time-dependent manner. Moreover, the accumulation of these stress markers in Cr(6+)-treated cells was over the Cr(3+)-treated ones. The decreased GSH level and increased activity of GPx were observed after 300 μM Cr(6+)-exposure compared with the untreated control, whereas there was no other change of GSH content in cells treated with Cr(3+) even at very high concentration. Exposure to both Cr(3+) and Cr(6+) resulted in the decrease of activities of SOD and catalase. Furthermore, the effect of Cr(6+) is stronger than that of Cr(3+). Null mutation sensitivity assay demonstrated that the gsh1 mutant was sensitive to Cr(6+) other than Cr(3+), the apn1 mutant is more sensitive to Cr(6+) than Cr(3+), and the rad1 mutant is sensitive to both Cr(6+) and Cr(3+). Therefore, Cr(3+) can be concluded to inhibit cell growth probably due to the damage of plasma membrane integrality in yeast. Although both tri- and hexavalent chromium can induce cytotoxicity and oxidative stress, the action mode of Cr(3+) is different from that of Cr(6+), and serious membrane damage caused by Cr(3+) is not the direct consequence of the increase of lipid peroxidation.