Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde.
Cancer Res
; 67(23): 11117-22, 2007 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-18056434
ABSTRACT
Formaldehyde is an aliphatic monoaldehyde and is a highly reactive environmental human carcinogen. Whereas humans are continuously exposed to exogenous formaldehyde, this reactive aldehyde is a naturally occurring biological compound that is present in human plasma at concentrations ranging from 13 to 97 micromol/L. It has been well documented that DNA-protein crosslinks (DPC) likely play an important role with regard to the genotoxicity and carcinogenicity of formaldehyde. However, little is known about which DNA damage response pathways are essential for cells to counteract formaldehyde. In the present study, we first assessed the DNA damage response to plasma levels of formaldehyde using chicken DT40 cells with targeted mutations in various DNA repair genes. Here, we show that the hypersensitivity to formaldehyde is detected in DT40 mutants deficient in the BRCA/FANC pathway, homologous recombination, or translesion DNA synthesis. In addition, FANCD2-deficient DT40 cells are hypersensitive to acetaldehyde, but not to acrolein, crotonaldehyde, glyoxal, and methylglyoxal. Human cells deficient in FANCC and FANCG are also hypersensitive to plasma levels of formaldehyde. These results indicate that the BRCA/FANC pathway is essential to counteract DPCs caused by aliphatic monoaldehydes. Based on the results obtained in the present study, we are currently proposing that endogenous formaldehyde might have an effect on highly proliferating cells, such as bone marrow cells, as well as an etiology of cancer in Fanconi anemia patients.
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Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
Proteína BRCA1
/
Reagentes de Ligações Cruzadas
/
Desinfetantes
/
Proteína do Grupo de Complementação D2 da Anemia de Fanconi
/
Formaldeído
Limite:
Animals
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos