Fanconi anemia complementation group A cells are hypersensitive to chromium(VI)-induced toxicity
| Autor: | Steven R. Patierno, Travis J. O’Brien, Jamie L. Fornsaglio, Susan Ceryak, Linan Ha, Daryl E. Pritchard, Susan K. Vilcheck |
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| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
Chromium
Male DNA Repair DNA repair Health Toxicology and Mutagenesis Cell Culture Techniques Caspase 3 Apoptosis DNA Adducts Fanconi anemia medicine Humans Caspase Carcinogen biology Phosphotransferases Public Health Environmental and Occupational Health Bone marrow failure Fibroblasts medicine.disease Molecular biology Carcinogens Environmental Cross-Linking Reagents Fanconi Anemia Biochemistry Cell culture Caspases biology.protein Research Article Penis |
| Zdroj: | Environmental Health Perspectives |
| ISSN: | 0091-6765 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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