Review of chromium (VI) apoptosis, cell-cycle-arrest, and carcinogenesis

A. Chiu, X. L. Shi, W. K.P. Lee, R. Hill, T. P. Wakeman, A. Katz, B. Xu, N. S. Dalal, J. D. Robertson, C. Chen, N. Chiu, L. Donehower

Research output: Contribution to journalReview articlepeer-review

79 Scopus citations


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.

Original languageEnglish
Pages (from-to)188-230
Number of pages43
JournalJournal of Environmental Science and Health - Part C Environmental Carcinogenesis and Ecotoxicology Reviews
Issue number3
StatePublished - Jul 2010

Bibliographical note

Funding 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.


  • apoptosis
  • chloride intracellular channel carrier
  • genomic plasticity
  • pentavalent chromium
  • senescence
  • somatic recombination
  • tetravalent chromium

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Cancer Research


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