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Carcinogenesis, Vol. 21, No. 4, 845-847, April 2000
© 2000 Oxford University Press

Short Communications

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

Helmut Bartsch3, David H. Phillips1, Jagadeesan Nair, Alan Hewer1, Gabriele Meyberg-Solomeyer2 and Eva-Maria Grischke2

Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany,
1 Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, UK and
2 Frauenklinik, Ruprecht-Karls-Universität, Heidelberg, Germany

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 TAM or toremifene (TOR), a TAM analogue and compared them with adducts formed by TAM in rat liver, where the drug induces tumours. DNA adducts were measured by TLC-32P-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 108 nucleotides (associated with 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 32P 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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