Expression of cytochrome P450 genes encoding enzymes active in the metabolism of tamoxifen in human uterine endometrium.
Pharmacol Toxicol
; 82(2): 93-7, 1998 Feb.
Article
em En
| MEDLINE
| ID: mdl-9498238
ABSTRACT
Long-term tamoxifen therapy is associated with increased risk of uterine endometrial cancer and benign alterations. Tamoxifen is metabolized to reactive intermediates by endometrial tissue, and tamoxifen therapy-induced DNA adducts have been found in human endometrium. Since metabolic activation is often catalyzed by cytochrome P450 (CYP) enzymes, the expression profile of individual xenobiotic-metabolizing CYP genes was studied in human uterine endometrium by reverse transcriptase-polymerase chain reaction. The following CYP mRNAs were detected CYP2B6, CYP2C, CYP2E1, CYP3A4, CYP3A5, CYP4B1, and CYP11A. Amplification of CYP1A1, CYP1A2, CYP2A6, CYP2D6, CYP2F1, CYP3A7, and CYP19 was not found. CYP3A5 and CYP4B1 transcripts were found only in samples from premenopausal women. These data suggest that the human endometrial epithelium has the potential of producing CYP enzymes known to generate genotoxic intermediates from tamoxifen and metabolites that affect oestrogen receptors.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Tamoxifeno
/
Antineoplásicos Hormonais
/
Sistema Enzimático do Citocromo P-450
/
Endométrio
/
Antagonistas de Estrogênios
Idioma:
En
Ano de publicação:
1998
Tipo de documento:
Article