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