Characterization of the major DNA adducts in the liver of rats chronically exposed to tamoxifen for 18 months

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 P-32-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. alpha-TAM-N-2-deoxyguanine (alpha-TAM-N-2-dG) and alpha-N-desmethyl TAM-N-2-deoxyguanine (alpha-N-dm-TAM-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 alpha-TAM-N-2-dG and the other fraction co-migrated with the alpha-N-dmTAM-N-2-dG. These findings have demonstrated that chronic exposure to tamoxifen induced the same major DNA adducts. i.e. alpha-TAM-N-2-dG and alpha-N-dmTAM-N-2-dG as those detected in acutely exposed rats. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.