Carcinogenesis, Vol. 20, No. 2, 339-342,
February 1999
© 1999 Oxford University Press
Short Communications |
Lack of evidence from HPLC 32P-post-labelling for tamoxifen–DNA adducts in the human endometrium
Imperial College School of Medicine, Division of Biomedical Sciences, Molecular Toxicology, London SW7 2AZ, UK,
1 Kliniek St Jan, Broekstraat 114, 1000 Brussels, Belgium,
2 St George's Hospital, Tooting SW17 0QT, UK,
3 Oulu University Hospital, 90220 Oulu, Finland,
4 Sahlgrenska Hospital, S-41345 Gothenburg, Sweden and
5 Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Belmont, Sutton, Surrey SM2 5NG, UK
Tamoxifen is associated with an increased incidence of endometrial cancer in 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 endometria, utilizing thin layer chromatography 32P-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) Cancer Res., 56, 1475–1479]. However, subsequent work utilizing HPLC 32P-post-labelling [Hemminki,K., Ranjaniemi,H., Lindahl,B. and Moberger,B. (1996) Cancer Res., 56, 4374–4377] suggested that very low levels could be detected. We have sought to investigate this question further by reproducing the HPLC methodology at two centres, and analysing endometrial DNA from 20 patients treated with 20 mg/day tamoxifen for between 22 and 65 months. Liver DNA isolated 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 were indistinguishable from those obtained with DNA from 14 untreated women and from six women taking toremifene, an analogue of tamoxifen.
Abbreviations: HPLC, high performance liquid chromatography; TLC, thin layer chromatography.
6 To whom correspondence should be addressed Email: p.carmichael{at}ic.ac.uk
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