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

Environ Health Perspect. 2002 Oct;110 Suppl 5(Suppl 5):773-7. doi: 10.1289/ehp.02110s5773.


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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis
  • Carcinogens, Environmental / toxicity*
  • Caspase 3
  • Caspases / pharmacology
  • Cell Culture Techniques
  • Chromium / toxicity*
  • Cross-Linking Reagents
  • DNA Adducts*
  • DNA Repair*
  • Fanconi Anemia / genetics*
  • Fanconi Anemia / physiopathology*
  • Fibroblasts / physiology
  • Humans
  • Male
  • Penis / cytology
  • Phosphotransferases / pharmacology


  • Carcinogens, Environmental
  • Cross-Linking Reagents
  • DNA Adducts
  • Chromium
  • chromium hexavalent ion
  • Phosphotransferases
  • CASP3 protein, human
  • Caspase 3
  • Caspases