IDENTIFICATION OF TAMOXIFEN-DNA ADDUCTS

We have developed a high performance liquid chromatography (HPLC) tech nique which separates tamoxifen-DNA adducts in rat liver into 12 peaks . Our results suggest that alpha-hydroxylation is the major route of a ctivation in rat Liver, whereas 4-hydroxylation represents a minor pat hway. In humans, adducts are absent or at low levels making detection a problem. Using HPLC, no tamoxifen adducts have been detected in huma n uterus and to improve sensitivity we are using [C-14]tamoxifen and a ccelerator mass spectrometry to detect adducts. Before surgery, patien ts take a capsule containing [C-14]tamoxifen and the DNA in excised ti ssues is analysed for [C-14], to assess the irreversible binding. (C) 1998 Elsevier Science Ltd; All rights reserved.