TY - JOUR
T1 - Characterization of the major DNA adducts in the liver of rats chronically exposed to tamoxifen for 18 months
AU - Firoz Firozi, Pervez
AU - Vulimiri, Suryanarayana V.
AU - Rajaniemi, Heli
AU - Hemminki, Kari
AU - Dragan, Yvonne
AU - Pitot, Henry C.
AU - Digiovanni, John
AU - Zhu, Yong Hong
AU - Li, Donghui
PY - 2000/4/14
Y1 - 2000/4/14
N2 - 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-N2-deoxyguanine (α-TAM-N2-dG) and α-N-desmethyl TAM-N2-deoxyguanine (α-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 α-TAM-N2-dG and the other fraction co-migrated with the α-N-dmTAM-N2-dG. These findings have demonstrated that chronic exposure to tamoxifen induced the same major DNA adducts, i.e. α-TAM-N2-dG and α-N-dmTAM-N2-dG as those detected in acutely exposed rats. Copyright (C) 2000 Elsevier Science Ireland Ltd.
AB - 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-N2-deoxyguanine (α-TAM-N2-dG) and α-N-desmethyl TAM-N2-deoxyguanine (α-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 α-TAM-N2-dG and the other fraction co-migrated with the α-N-dmTAM-N2-dG. These findings have demonstrated that chronic exposure to tamoxifen induced the same major DNA adducts, i.e. α-TAM-N2-dG and α-N-dmTAM-N2-dG as those detected in acutely exposed rats. Copyright (C) 2000 Elsevier Science Ireland Ltd.
KW - Chronic exposure
KW - DNA adducts
KW - Rat liver
KW - Tamoxifen
KW - α-N-desmethyl TAM-N-deoxyguanine
KW - α-TAM-N-deoxyguanine
UR - http://www.scopus.com/inward/record.url?scp=0034647097&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034647097&partnerID=8YFLogxK
U2 - 10.1016/S0009-2797(00)00151-4
DO - 10.1016/S0009-2797(00)00151-4
M3 - Article
C2 - 10826652
AN - SCOPUS:0034647097
SN - 0009-2797
VL - 126
SP - 33
EP - 43
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
IS - 1
ER -