Journal Article

Lack of evidence from HPLC <sup>32</sup>P-post-labelling for tamoxifen–DNA adducts in the human endometrium

Paul L. Carmichael, Shahida Sardar, Neil Crooks, Patrick Neven, Ingrid Van Hoof, Austin Ugwumadu, Tom Bourne, Eija Tomas, Pär Hellberg, Alan J. Hewer and David H. Phillips

in Carcinogenesis

Volume 20, issue 2, pages 339-342
Published in print February 1999 | ISSN: 0143-3334
Published online February 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.2.339
Lack of evidence from HPLC 32P-post-labelling for tamoxifen–DNA adducts in the human endometrium

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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.

Keywords: HPLC, high performance liquid chromatography; TLC, thin layer chromatography.

Journal Article.  2303 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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