Abstract
Our previous study has shown that chronic exposure to tamoxifen (TAM) induced formation of high levels of DNA adducts in the liver, the target tissue of TAM-induced carcinogenesis in rats. One of the major DNA adducts (spot 1), as detected by 32P-postlabeling, accounted for 53% of the total adducts. To characterize this major adduct, the current study has compared spot 1 with two previously identified TAM-DNA adducts, i.e. α-TAM- N 2-deoxyguanine (α-TAM- N 2-dG) and α- N-desmethyl TAM- N 2-deoxyguanine (α- N-dmTAM- N 2-dG) by various rechromatography methods. It was found that spot 1 was further resolved into two fractions during rechromatography analysis, one fraction co-migrated with the α-TAM- N 2-dG and the other fraction co-migrated with the α- N-dmTAM- N 2–dG. These findings have demonstrated that chronic exposure to tamoxifen induced the same major DNA adducts, i.e. α-TAM- N 2-dG and α- N-dmTAM- N 2-dG as those detected in acutely exposed rats.
Published Version
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