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Carcinogenesis, Vol. 20, No. 2, 305-309, February 1999
© 1999 Oxford University Press

Identification of the major tamoxifen–DNA adducts in rat liver by mass spectroscopy

Heli Rajaniemi3, Ilpo Rasanen1, Pertti Koivisto2, Kimmo Peltonen2 and Kari Hemminki

Department of Biosciences at Novum, Karolinska Institute, Novum 141 57 Huddinge, Sweden,
1 University of Helsinki, Department of Forensic Medicine, FIN-00014 Helsinki and
2 Institute of Occupational Health, Topeliuksenkatu 41 aA, FIN-00250 Helsinki, Finland

We present here the first mass spectroscopic (MS) identification of the main tamoxifen-induced DNA adducts in rat liver. The two main adducts were isolated by high-performance liquid chromatography (HPLC) and identified by MS, MS–MS and ultraviolet spectroscopy. Adduct 1 was the N-desmethyltamoxifen–deoxyguanosine adduct in which the {alpha}-position of the metabolite N-desmethyltamoxifen is linked covalently to the amino group of deoxyguanosine. Adduct 2 was confirmed to be the trans isomer of {alpha}-(N2-deoxyguanosinyl)tamoxifen, as previously suggested by co-chromatography.

Abbreviations: dGMP, deoxyguanosine 5'-monophosphate; HPLC, high-performance liquid chromatography; MS, mass spectroscopy; NP1, nuclease P1.

3 To whom correspondence should be addressed Email: heli.rajaniemi{at}cnt.ki.se


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