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Complexities of chromium carcinogenesis: role of cellular response, repair and recovery mechanisms.

Publication ,  Journal Article
O'Brien, TJ; Ceryak, S; Patierno, SR
Published in: Mutat Res
December 10, 2003

Certain hexavalent chromium (Cr(VI))-containing compounds are recognized occupational human lung carcinogens and may pose an environmental health risk. The carcinogenicity of Cr(VI) is targeted to particulate forms of moderate to low solubility. Soluble Cr(VI) oxyanions in the immediate cellular microenvironment traverse the cell membrane by non-specific anionic transporters. Cr(VI) is reductively metabolized within cells by agents including ascorbic acid (Asc), glutathione (GSH) and cysteine (Cys). During Cr(VI) reduction, a diverse range of genetic lesions are generated including Cr-DNA binary (mono) adducts, Cr-DNA ternary adducts, DNA protein crosslinks (DPCs), bi-functional (DNA interstrand crosslinks (ICLs)) adducts, single-strand breaks (SSBs) and oxidized bases. Some forms of Cr damage, such as ICLs, present physical barriers to DNA replication/transcription and, thus, likely promote a terminal cell fate such as apoptosis or terminal growth arrest. Other lesions, such as ternary DNA adducts, are potentially pre-mutagenic. Cr(VI) exposure elicits a classical DNA damage response within cells including activation of the p53 signaling pathway and cell cycle arrest or apoptosis. Moreover, Cr(VI) also induces the ATM-dependent DNA damage response pathway which is paradoxically required for both apoptosis and survival after Cr(VI) insult. In yeast, moderately cytotoxic concentrations of Cr(VI) result in an initial G1 arrest and delayed S phase progression, whereas less toxic levels of Cr(VI) induce G2 arrest, which requires homologous recombination for exit and survival. The past several years has witnessed many important advances in our understanding of the genetic/cellular damage produced by exposure to Cr(VI). Further information is needed regarding the potential involvement of oxygen radicals in Cr genotoxicity, the specific DNA repair pathways activated by Cr and the complex signaling mechanisms involved in the cellular response to Cr(VI). These pertinent issues must be considered in relation to the potential role that each plays in the induction of human respiratory tract cancer by particulate Cr(VI) compounds.

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Published In

Mutat Res

DOI

ISSN

0027-5107

Publication Date

December 10, 2003

Volume

533

Issue

1-2

Start / End Page

3 / 36

Location

Netherlands

Related Subject Headings

  • Oncology & Carcinogenesis
  • Mutagens
  • Humans
  • DNA Replication
  • DNA Repair
  • DNA Damage
  • Chromium Compounds
  • Chromium
  • Carcinogens, Environmental
  • Air Pollutants, Occupational
 

Citation

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O’Brien, T. J., Ceryak, S., & Patierno, S. R. (2003). Complexities of chromium carcinogenesis: role of cellular response, repair and recovery mechanisms. Mutat Res, 533(1–2), 3–36. https://doi.org/10.1016/j.mrfmmm.2003.09.006
O’Brien, Travis J., Susan Ceryak, and Steven R. Patierno. “Complexities of chromium carcinogenesis: role of cellular response, repair and recovery mechanisms.Mutat Res 533, no. 1–2 (December 10, 2003): 3–36. https://doi.org/10.1016/j.mrfmmm.2003.09.006.
O’Brien TJ, Ceryak S, Patierno SR. Complexities of chromium carcinogenesis: role of cellular response, repair and recovery mechanisms. Mutat Res. 2003 Dec 10;533(1–2):3–36.
O’Brien, Travis J., et al. “Complexities of chromium carcinogenesis: role of cellular response, repair and recovery mechanisms.Mutat Res, vol. 533, no. 1–2, Dec. 2003, pp. 3–36. Pubmed, doi:10.1016/j.mrfmmm.2003.09.006.
O’Brien TJ, Ceryak S, Patierno SR. Complexities of chromium carcinogenesis: role of cellular response, repair and recovery mechanisms. Mutat Res. 2003 Dec 10;533(1–2):3–36.
Journal cover image

Published In

Mutat Res

DOI

ISSN

0027-5107

Publication Date

December 10, 2003

Volume

533

Issue

1-2

Start / End Page

3 / 36

Location

Netherlands

Related Subject Headings

  • Oncology & Carcinogenesis
  • Mutagens
  • Humans
  • DNA Replication
  • DNA Repair
  • DNA Damage
  • Chromium Compounds
  • Chromium
  • Carcinogens, Environmental
  • Air Pollutants, Occupational