EXPRESSION OF CYTOCHROME-P450 GENES ENCODING ENZYMES ACTIVE IN THE METABOLISM OF TAMOXIFEN IN HUMAN UTERINE ENDOMETRIUM

Long-term tamoxifen therapy is associated with increased risk of uteri ne endometrial cancer and benign alterations. Tamoxifen is metabolized to reactive intermediates by endometrial tissue, and tamoxifen therap y-induced DNA adducts have been found in human endometrium. Since meta bolic 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-pol ymerase chain reaction. The following CYP mRNAs were detected: CYP2B6, CYP2C, CYP2E1, CYP3A4, CYP3A5, CYP4B1, and CYP11A. Amplification of C YP1A1, CYP1A2, CYP2A6, CYP2D6, CYP2F1, CYP3A7, and CYP19 was not found . CYP3A5 and CYP4B1 transcripts were found only in samples from premen opausal women. These data suggest that the human endometrial epitheliu m has the potential of producing CYP enzymes known to generate genotox ic intermediates from tamoxifen and metabolites that affect oestrogen receptors.