Hexavalent chromium combines with glutathione in chloride intracellular channel carrier to form tetravalent and pentavalent chromium in plasma and organelle membranes. It also combines with NADH/NADPH to form pentavalent chromium in mitochondria. Tetravalent- and pentavalent- chromium (directly and indirectly) mediated DNA double strand breaks activate DNA damage signaling sensors: DNA-dependent-protein-kinase signals p53-dependent intrinsic mitochondrial apoptosis, and ataxia-telangiectasia-mutated and ataxia-telangiectasia-Rad3-related signal cell-arrest for DNA repair. Tetravalent chromium may be the most potent species since it causes DNA breaks and somatic recombination, but not apoptosis. Upon further failure of apoptosis and senescence/DNA-repair, damaged cells may become immortal with loss-of-heterozygosity and genetic plasticity.
|Number of pages||43|
|Journal||Journal of Environmental Science and Health - Part C Environmental Carcinogenesis and Ecotoxicology Reviews|
|State||Published - Jul 2010|
Bibliographical noteFunding Information:
All the authors with to acknowledge the support of their respective institutions. Dr. Xianglin Shi wishes especially to acknowledge the generous support of NIH grant 1R01CA116697.
- chloride intracellular channel carrier
- genomic plasticity
- pentavalent chromium
- somatic recombination
- tetravalent chromium
ASJC Scopus subject areas
- Health, Toxicology and Mutagenesis
- Cancer Research