title: Review of chromium (VI) apoptosis, cell-cycle-arrest, and carcinogenesis.
abstract: 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.
authors.affiliation: National Center for Environmental Assessment DC, US Environmental Protection Agency, Washington, DC 20460, USA. Chiu.Arthur@epa.gov
authors.forename: A
authors.initials: A
authors.lastname: Chiu
authors.forename: X L
authors.initials: XL
authors.lastname: Shi
authors.forename: W K P
authors.initials: WK
authors.lastname: Lee
authors.forename: R
authors.initials: R
authors.lastname: Hill
authors.forename: T P
authors.initials: TP
authors.lastname: Wakeman
authors.forename: A
authors.initials: A
authors.lastname: Katz
authors.forename: B
authors.initials: B
authors.lastname: Xu
authors.forename: N S
authors.initials: NS
authors.lastname: Dalal
authors.forename: J D
authors.initials: JD
authors.lastname: Robertson
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.forename: N
authors.initials: N
authors.lastname: Chiu
authors.forename: L
authors.initials: L
authors.lastname: Donehower
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002857:Chromium / Q000633:toxicity*; D006801:Humans
chemical_list: D002857:Chromium