Excision of tamoxifen-DNA adducts by the human nucleotide excision repair system.
Cancer Res
; 60(10): 2607-10, 2000 May 15.
Article
en En
| MEDLINE
| ID: mdl-10825130
The antiestrogen tamoxifen is used in the treatment of breast cancer and has recently been recommended as a chemopreventive drug for women at high risk for breast cancer. However, women treated with the drug have an increased incidence of endometrial cancer. It has been suggested that this endometrial cancer might result from mutagenic DNA adducts, which are formed by electrophilic tamoxifen species generated by metabolic activation of the drug. Because the frequency of damage-induced mutations is strongly dependent on the repairability of the lesion, we investigated the repair of the major tamoxifen-DNA adducts by the human nucleotide excision repair system. Using the reconstituted human excision repair system and synthetic DNA substrates, we found that the four types of tamoxifen-DNA adducts detected in the endometrium were repaired with moderate to poor efficiency by nucleotide excision repair. It is concluded that individual variations in repair capacity may play a role in the development of tamoxifen-induced endometrial cancer.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tamoxifeno
/
Aductos de ADN
/
Antineoplásicos Hormonales
/
Reparación del ADN
Límite:
Female
/
Humans
Idioma:
En
Revista:
Cancer Res
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos