VI.4 Identification of Tamoxifen-DNA Adducts

Abstract We have developed a high performance liquid chromatography (HPLC) technique which separates tamoxifen-DNA adducts in rat liver into 12 peaks. Our results suggest that α-hydroxylation is the major route of activation in rat liver, whereas 4-hydroxylation represents a minor pathway. In humans, adducts are absent or at low levels making detection a problem. Using HPLC, no tamoxifen adducts have been detected in human uterus and to improve sensitivity we are using [ 14 C]tamoxifen and accelerator mass spectrometry to detect adducts. Before surgery, patients take a capsule containing [ 14 C]tamoxifen and the DNA in excised tissues is analysed for [ 14 C], to assess the irreversible binding.