Arsenite enhances the benzo[a]pyrene diol epoxide (BPDE)-induced mutagenesis with no marked effect on repair of BPDE-DNA adducts in human lung cells.
Toxicol In Vitro
; 23(5): 897-905, 2009 Aug.
Article
en En
| MEDLINE
| ID: mdl-19470404
Arsenite effects on the benzo[a]pyrene diol epoxide (BPDE)-DNA adduct-induced mutation were evaluated in three human lung cell-lines--A549 (wild-type p53), WI38-VA13 (p53 inhibited by SV40 large-T antigen), and H1299 (p53-null)--by using the pSP189 shuttle vector, which carries a mutation target supF gene. Arsenite alone had no significant effect on the spontaneous supF mutation. BPDE modification of pSP189 enhanced the mutation rates of supF 4.37-fold, 2.96-fold, and 1.95-fold for A549, WI38-VA13, and H1299, respectively. Arsenite potentiated the BPDE-induced mutation rates of supF 2.30-fold, 2.31-fold, and 2.35-fold in A549, WI38-VA13, and H1299, respectively. These results suggest that arsenite potentiates the BPDE-induced supF mutation via a p53-independent mechanism. By using the host cell reactivation assay, we evaluated arsenite effect on repair of BPDE-DNA adducts. We found that the arsenite treatments resulting in relative survival rates 65% had no significant effect on repair of BPDE-DNA adducts, indicating that p53 status did not significantly affect the repair of BPDE-DNA adducts. This study reveals that arsenite enhances the BPDE-DNA adduct-induced mutagenesis with no marked effect on repair of BPDE-DNA adducts, suggesting that arsenic may act as a co-mutagen to promote the development of human lung cancer.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
7,8-Dihidro-7,8-dihidroxibenzo(a)pireno 9,10-óxido
/
Compuestos de Sodio
/
Arsenitos
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Aductos de ADN
Límite:
Humans
Idioma:
En
Revista:
Toxicol In Vitro
Asunto de la revista:
TOXICOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Taiwán
Pais de publicación:
Reino Unido