Journal article
Sulfation of alpha-hydroxytamoxifen catalyzed by human hydroxysteroid sulfotransferase results in tamoxifen-DNA adducts
Carcinogenesis (New York), Vol.19(11), pp.2007-2011
11/1998
DOI: 10.1093/carcin/19.11.2007
PMID: 9855017
Abstract
The formation of tamoxifen (TAM)-derived DNA adducts was investigated by incubation of DNA with (E)-alpha-hydroxytamoxifen [(E)-alpha-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 alpha-(N2-deoxyguanosinyl)tamoxifen 3'-monophosphate (dG3'P-N2-TAM), the major adduct was identified chromatographically as an epimer of the transform 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 alpha-OHTAM catalyzed by hHST results in the formation of dG-N2-TAMs, highly miscoding lesions, in human tissues.
Details
- Title: Subtitle
- Sulfation of alpha-hydroxytamoxifen catalyzed by human hydroxysteroid sulfotransferase results in tamoxifen-DNA adducts
- Creators
- S Shibutani - Stony Brook UniversityP M ShawN SuzukiL DasaradhiM W DuffelI Terashima
- Resource Type
- Journal article
- Publication Details
- Carcinogenesis (New York), Vol.19(11), pp.2007-2011
- DOI
- 10.1093/carcin/19.11.2007
- PMID
- 9855017
- NLM abbreviation
- Carcinogenesis
- ISSN
- 0143-3334
- eISSN
- 1460-2180
- Grant note
- R01 CA038683 / NCI NIH HHS ES09418 / NIEHS NIH HHS CA38683 / NCI NIH HHS
- Language
- English
- Date published
- 11/1998
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984303161902771
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