Comparative Studies of Tri- and Hexavalent Chromium Cytotoxicity and Their Effects on Oxidative State of Saccharomyces cerevisiae Cells

Abstract

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 Cr³⁺ or Cr⁶⁺, and Cr⁶⁺ significantly increased the lethal rate compared with Cr³⁺. Both Cr³⁺ and Cr⁶⁺ can enter into the yeast cells. The percent of propidium iodide permeable cells treated with Cr³⁺ is almost five times as that treated with the same concentration of Cr⁶⁺. Levels of TBARS, O₂ ⁻, and carbonyl protein were significantly increased in both Cr⁶⁺- and Cr³⁺-treated cells in a concentration- and time-dependent manner. Moreover, the accumulation of these stress markers in Cr⁶⁺-treated cells was over the Cr³⁺-treated ones. The decreased GSH level and increased activity of GPx were observed after 300 μM Cr⁶⁺-exposure compared with the untreated control, whereas there was no other change of GSH content in cells treated with Cr³⁺ even at very high concentration. Exposure to both Cr³⁺ and Cr⁶⁺ resulted in the decrease of activities of SOD and catalase. Furthermore, the effect of Cr⁶⁺ is stronger than that of Cr³⁺. Null mutation sensitivity assay demonstrated that the gsh1 mutant was sensitive to Cr⁶⁺ other than Cr³⁺, the apn1 mutant is more sensitive to Cr⁶⁺ than Cr³⁺, and the rad1 mutant is sensitive to both Cr⁶⁺ and Cr³⁺. Therefore, Cr³⁺ 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 Cr³⁺ is different from that of Cr⁶⁺, and serious membrane damage caused by Cr³⁺ is not the direct consequence of the increase of lipid peroxidation.