Deficient repair of particulate hexavalent chromium-induced DNA double strand breaks leads to neoplastic transformation.
Mutat Res
; 649(1-2): 230-8, 2008 Jan 08.
Article
en En
| MEDLINE
| ID: mdl-18023605
ABSTRACT
Hexavalent chromium (Cr(VI)) is a potent respiratory toxicant and carcinogen. The most carcinogenic forms of Cr(VI) are the particulate salts such as lead chromate, which deposit and persist in the respiratory tract after inhalation. We demonstrate here that particulate chromate induces DNA double strand breaks in human lung cells with 0.1, 0.5, and 1 microg/cm(2) lead chromate inducing 1.5, 2, and 5 relative increases in the percent of DNA in the comet tail, respectively. These lesions are repaired within 24 h and require Mre11 expression for their repair. Particulate chromate also caused Mre11 to co-localize with gamma-H2A.X and ATM. Failure to repair these breaks with Mre11-induced neoplastic transformation including loss of cell contact inhibition and anchorage-independent growth. A 5-day exposure to lead chromate induced loss of cell contact inhibition in a concentration-dependent manner with 0, 0.1, 0.5, and 1 microg/cm(2) lead chromate inducing 1, 78, and 103 foci in 20 dishes, respectively. These data indicate that Mre11 is critical to repairing particulate Cr(VI)-induced double strand breaks and preventing Cr(VI)-induced neoplastic transformation.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transformación Celular Neoplásica
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Cromo
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Reparación del ADN
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Roturas del ADN de Doble Cadena
Límite:
Humans
Idioma:
En
Revista:
Mutat Res
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos