| Autor: |
Shibutani, S, Shaw, PM, Suzuki, N, Dasaradhi, L, Duffel, MW, Terashima, I |
| Zdroj: |
Carcinogenesis; Nov1998, Vol. 19 Issue 11, p2007-2011, 5p |
| Abstrakt: |
The formation of tamoxifen (TAM)-derived DNA adducts was investigated by incubation of DNA with (E)-α-hydroxytamoxifen [(E)-α-OHTAM], 3′-phosphoadenosine 5′-phosphosulfate (PAPS), and human recombinant sulfotransferase. Using 32P-post-labeling and HPLC analysis, two TAM-DNA adducts were detected in incubations that included the human hydroxysteroid sulfotransferase SULT2A1 (hHST). When compared with standards of stereoisomers of α-(N2-deoxyguanosinyl)tamoxifen 3′-monophosphate (dG3′p-N2-TAM), the major adduct was identified chromatographically as an epimer of the trans-form of dG-N2-TAM, and the minor adduct was identified as an epimer of the cis-form. The amount of TAM adducts formed by hHST was approximately three times less than that formed by an equivalent amount of rat hydroxysteroid (alcohol) sulfotransferase a. These results indicate that sulfation of α-OHTAM catalyzed by hHST results in the formation of dG-N2-TAMs, highly miscoding lesions, in human tissues. [ABSTRACT FROM PUBLISHER] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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