Molecular mechanisms of Cr(VI)-induced carcinogenesis.
Although Cr(VI)-containing compounds are well documented carcinogens, their mechanism of action is still not well understood. Recent studies have suggested that reduction of Cr(VI) to its lower oxidation states and related free radical reactions play an important role in Cr(VI)-induced carcinogenesis. This article summarizes recent studies from our laboratory on (a) the reduction of Cr(VI) by ascorbate, diol- and thiol-containing molecules, certain flavoenzymes, cell organelles, intact cells, and whole animals; (b) free radical production in both non-cellular and cellular systems; and (c) Cr(VI)-induced DNA damage, activation of nuclear transcription factor KB (NF-kappaB), activator protein-1, p53, hypoxia-inducible factor-1, vascular endothelial growth factor, tyrosine phosphorylation, apoptosis, cell growth arrest, and gene expression profile.
Ding
Min
M
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA.
Shi
Xianglin
X
D000818:Animals; D002273:Carcinogens / Q000378:metabolism / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002857:Chromium / Q000378:metabolism / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D005609:Free Radicals / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D010084:Oxidation-Reduction
D002273:Carcinogens; D005609:Free Radicals; D002857:Chromium; C074702:chromium hexavalent ion