title: Characterization of the major DNA adducts in the liver of rats chronically exposed to tamoxifen for 18 months.
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. alpha-TAM-N2-deoxyguanine (alpha-TAM-N2-dG) and alpha-N-desmethyl TAM-N2-deoxyguanine (alpha-N-dmTAM-N2-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-N2-dG and the other fraction co-migrated with the alpha-N-dmTAM-N2-dG. These findings have demonstrated that chronic exposure to tamoxifen induced the same major DNA adducts, i.e. alpha-TAM-N2-dG and alpha-N-dmTAM-N2-dG as those detected in acutely exposed rats.
authors.affiliation: Department of Gastrointestinal Oncology and Digestive Diseases, The University of Texas, MD Anderson Cancer Center, Houston 77030, USA.
authors.forename: P F
authors.initials: PF
authors.lastname: Firozi
authors.forename: S V
authors.initials: SV
authors.lastname: Vulimiri
authors.forename: H
authors.initials: H
authors.lastname: Rajaniemi
authors.forename: K
authors.initials: K
authors.lastname: Hemminki
authors.forename: Y
authors.initials: Y
authors.lastname: Dragan
authors.forename: H C
authors.initials: HC
authors.lastname: Pitot
authors.forename: J
authors.initials: J
authors.lastname: DiGiovanni
authors.forename: Y H
authors.initials: YH
authors.lastname: Zhu
authors.forename: D
authors.initials: D
authors.lastname: Li
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000378:metabolism / Q000633:toxicity*; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D018736:DNA Adducts / Q000032:analysis*; D005260:Female; D008099:Liver / Q000737:chemistry / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000378:metabolism / Q000633:toxicity*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D002273:Carcinogens; D018736:DNA Adducts; D013629:Tamoxifen