Lack of evidence from HPLC P-32-post-labelling for tamoxifen-DNA adducts in the human endometrium

Tamoxifen is associated with an increased incidence of endometrial cancer i n women. It is also a potent carcinogen in rat liver and forms covalent DNA adducts in this tissue. A previous study exploring DNA adducts in human en dometria, utilizing thin layer chromatography P-32-post-labelling, found no evidence for adducts in tamoxifen-treated women [Carmichael,P.L., Ugwumadu ,A.H.N., Neven,P., Hewer,A,J,, Poon,G,K, and Phillips,D.H. (1996) Cancel Re s., 56, 1475-1479]. However, subsequent work utilizing HPLC P-32-post-label ling [Hemminki,K., Ranjaniemi,H., Lindahl,B, and Moberger,B, (1996) Cancer Res., 56, 4374-4377] suggested that very low levels could be detected. We h ave sought to investigate this question further by reproducing the HPLC met hodology at two centres, and analysing endometrial DNA from 20 patients tre ated with 20 mg/day tamoxifen for between 22 and 65 months. Liver DNA isola ted from tamoxifen-treated rats was used as a positive control. We found no convincing evidence for tamoxifen-derived DNA adducts in human endometrium , HPLC elution profiles of post-labelled DNA from tamoxifen-treated women w ere indistinguishable from those obtained with DNA from 14 untreated women and from six women taking toremifene, an analogue of tamoxifen.