Lack of evidence for tamoxifen- and toremifene-DNA adducts in lymphocytes of treated patients

被引:22
作者
Bartsch, H
Phillips, DH
Nair, J
Hewer, A
Meyberg-Solomeyer, G
Grischke, EM
机构
[1] German Canc Res Ctr, DKFZ, Div Toxicol & Canc Risk Factors, D-69120 Heidelberg, Germany
[2] Inst Canc Res, Haddow Labs, Sutton, Surrey, England
[3] Univ Heidelberg, Frauenklin, D-6900 Heidelberg, Germany
关键词
D O I
10.1093/carcin/21.4.845
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Tamoxifen (TAM) is used for the adjuvant treatment of women with breast cancer and has also been recommended as a chemopreventive agent. Among unwanted side effects, TAM was shown to increase endometrial cancer in treated women by mechanisms that are not yet clearly understood. We studied DNA adducts in lymphocytes of female breast cancer patients treated with TAR;I or toremifene (TOR), a TAM analogue and compared them with adducts formed by TAM in rat liver, where the drug induces tumours. DNA adducts mere measured by TLC-P-32-post-labelling assays. After TLC, all DNA samples including DNA from untreated healthy women showed a faint radioactive zone, where the positive control DNA adducts isolated from the liver of rats treated with TAM migrated. The relative adduct levels were calculated from the radioactivity present in this zone. Means +/- SD of adduct levels per 10(8) nucleotides (associated,vith this area) were for untreated volunteers (control) 1.83 +/- 1.41 (n = 13), for TAM treatment 2.17 +/- 3.04(n = 25) and for TOR treatment 1.18 +/- 1.05 (n = 8), Most of the human samples were further analysed by HPLC after labelling with P-32 in order to compare adducts in human DNA with those in liver DNA isolated from TAM-treated rats. None of the human samples showed any peaks at retention times where putative TAM-DNA adducts were eluted, In conclusion, lymphocyte DNA from female patients treated at therapeutic levels did not show evidence of the formation of TAM- or TOR-DNA adducts.
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页码:845 / 847
页数:3
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