Fanconi anemia complementation group A cells are hypersensitive to chromium(VI)-induced toxicity.

Published

Journal Article

Fanconi anemia (FA) is an autosomal recessive disorder characterized by diverse developmental abnormalities, progressive bone marrow failure, and a markedly increased incidence of malignancy. FA cells are hypersensitive to DNA cross-linking agents, suggesting a general defect in the repair of DNA cross-links. Some forms of hexavalent chromium [Cr(VI)] are implicated as respiratory carcinogens and induce several types of DNA lesions, including ternary DNA-Cr-DNA interstrand cross-links (Cr-DDC). We hypothesized that human FA complementation group A (FA-A) cells would be hypersensitive to Cr(VI) and Cr(VI)-induced apoptosis. Using phosphatidylserine translocation and caspase-3 activation, human FA-A fibroblasts were found to be markedly hypersensitive to chromium-induced apoptosis compared with CRL-1634 cells, which are normal human foreskin fibroblasts (CRL). The clonogenicity of FA-A cells was also significantly decreased compared with CRL cells after Cr(VI) treatment. There was no significant difference in either Cr(VI) uptake or Cr-DNA adduct formation between FA-A and CRL cells. These results show that FA-A cells are hypersensitive to Cr(VI) and Cr-induced apoptosis and that this hypersensitivity is not due to increased Cr(VI) uptake or increased Cr-DNA adduct formation. The results also suggest that Cr-DDC may be proapoptotic lesions. These results are the first to show that FA cells are hypersensitive to an environmentally relevant DNA cross-linking agent.

Full Text

Duke Authors

Cited Authors

  • Vilcheck, SK; O'Brien, TJ; Pritchard, DE; Ha, L; Ceryak, S; Fornsaglio, JL; Patierno, SR

Published Date

  • October 2002

Published In

Volume / Issue

  • 110 Suppl 5 /

Start / End Page

  • 773 - 777

PubMed ID

  • 12426130

Pubmed Central ID

  • 12426130

International Standard Serial Number (ISSN)

  • 0091-6765

Digital Object Identifier (DOI)

  • 10.1289/ehp.02110s5773

Language

  • eng

Conference Location

  • United States