Role of the Fancg gene in protecting cells from particulate chromate-induced chromosome instability

Laura C. Savery, Eliza Grlickova-Duzevik, Sandra S. Wise, W. Douglas Thompson, John M. Hinz, Larry H. Thompson, John Pierce Wise

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Particulate hexavalent chromium (Cr(VI)) is a known human lung carcinogen. Cr(VI)-induced tumors exhibit chromosome instability (CIN), but the mechanisms underlying these effects are unknown. We investigated a possible role for the Fanconi anemia (FA) pathway in particulate Cr(VI)-induced chromosomal damage by focusing on the Fancg gene, which plays an important role in cellular resistance to DNA interstrand crosslinks. We used the isogenic Chinese hamster ovary (CHO) KO40 fancg mutant compared with parental and gene-complemented cells. We found that fancg cells treated with lead chromate had lower intracellular Cr ion levels than control cell lines. Accounting for differences of Cr ion levels between cell lines, we discovered that fancg cells treated with lead chromate had increased cytotoxicity and chromosomal aberrations, which was not observed after restoring the Fancg gene. Chromosomal damage was manifest as increased total chromosome damage and percent metaphases with damage, specifically an increase in chromatid and isochromatid breaks. We conclude that Fancg protects cells from particulate Cr(VI)-induced cytotoxicity and chromosome damage, which is consistent with the known sensitivity of fancg cells to crosslinking damage and the ability of Cr(VI) to produce crosslinks.

Original languageEnglish (US)
Pages (from-to)120-127
Number of pages8
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume626
Issue number1-2
DOIs
StatePublished - Jan 10 2007
Externally publishedYes

Keywords

  • Chromosome instability (CIN)
  • FANCG
  • Fanconi anemia pathway
  • Hexavalent chromium (Cr(VI))
  • Lead chromate

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Genetics

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  • Cite this

    Savery, L. C., Grlickova-Duzevik, E., Wise, S. S., Thompson, W. D., Hinz, J. M., Thompson, L. H., & Wise, J. P. (2007). Role of the Fancg gene in protecting cells from particulate chromate-induced chromosome instability. Mutation Research - Genetic Toxicology and Environmental Mutagenesis, 626(1-2), 120-127. https://doi.org/10.1016/j.mrgentox.2006.09.005