Carcinogenic chromium(VI)‐induced protein oxidation and lipid peroxidation: implications in DNA–protein crosslinking

Abstract

Hexavalent chromium [Cr(VI)] compounds are Group-I human carcinogens. Cr(VI)-induced DNA-protein crosslinks (DPCs) have been implicated in the mutagenic and carcinogenic effects of Cr(VI). Although multiple mechanisms have been suggested for Cr(VI)-induced DNA-protein crosslinking, the mechanism of formation of DNA-protein crosslinks is not well understood. In this study, we explored the hypothesis that Cr(VI)-induced DPCs could be formed via generation of protein carbonyls and malonaldehyde (MDA) through protein oxidation and lipid peroxidation, respectively. Treatment of human leukemic T-lymphocyte MOLT4 cells with potassium chromate induced the formation of protein carbonyls and DPCs within 2 h, but increased the level of MDA only after 4 h, in a dose-dependent manner. Chromate treatment of MOLT4 cell homogenates also resulted in increased formation of MDA and protein carbonyls in a dose-dependent manner. EPR spectrometry in combination with spin trapping techniques revealed that reaction of Cr(VI) with biological reductants such as NADPH, glutathione reductase or H(2)O(2) generates Cr(V) and (*)OH radicals. Pretreatment of cells with antioxidants such as alpha-tocopherol or Tiron inhibited chromate-induced increase in formation of protein carbonyls, MDA and DPCs, but pretreatment of cells with riboflavin or 3-aminotriazole, a catalase inhibitor, had the opposite effect. Our results, for the first time, demonstrate that Cr(VI) exposure increases the cellular level of protein carbonyls and that Cr(VI)-induced DPCs may be formed, at least in part, via generation of protein carbonyls.

Studies on the genotoxic effect of chromium oxide (Cr VI): Interaction with deoxyribonucleic acid in solution

“…However the precise mechanism of chromium carcinogenicity remains unclear. It has been suggested that Cr (VI) mediates a majority of its cytotoxic and genotoxic effects by interacting with DNA and inhibiting replication and transcription [26,27]. The present study describes an attempt to characterize the interaction of chromium oxide with DNA molecule in solution to elucidate genotoxicity of this metal.…”

Chromium(III) oxide nanoparticles induced remarkable oxidative stress and apoptosis on culture cells

“…The reduction of hexavalent chromium to trivalent chromium produces reactive oxygen species (ROS), resulting in oxidization of lipids and proteins. The lipid peroxide and oxidized proteins induce metabolic dysfunction and chromosomal variation (Bagchi et al,2002; Mattagajasingh et al,2008). Compared with hexavalent chromium, the cellular influences of trivalent chromium are less significant because trivalent chromium is more chemically stable than hexavalent chromium.…”

Linking protein oxidation to environmental pollutants: Redox proteomic approaches

“…Additionally, Mattagajasingh et al pointed out an enhanced protein carbonylation upon Cr(VI) treatment of human leukemic T-lymphocytes and suggested that such a phenomenon may contribute to Cr(VI)-induced DNA-protein crosslinking [55].…”