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Title: Is tamoxifen a genotoxic carcinogen in women?
Authors: Brown, Karen
First Published: 7-Jun-2009
Publisher: Oxford University Press (OUP)
Citation: Mutagenesis, 2009, 24 (5), pp. 391-404.
Abstract: The anti-oestrogen tamoxifen, which is widely used in the treatment of breast cancer and is also approved for the prevention of this disease, causes an increased incidence of endometrial cancer in women. The ability of tamoxifen to induce endometrial tumours and the underlying carcinogenic mechanisms have been a subject of intense interest over the last ∼20 years. They are central to the assessment of risks versus benefits for the drug, especially in a chemopreventive context. This review outlines the clinical justification for using tamoxifen as a chemopreventive agent and describes the genotoxic mechanisms considered responsible for tamoxifen-induced tumours in rat liver and how these might relate to women. In rat hepatic tissue, tamoxifen is metabolically activated via α-hydroxylation and sulphate conjugation to give a reactive species that binds to DNA predominantly at the N2-position of guanine, producing pro-mutagenic lesions. Whether tamoxifen–DNA adducts contribute similarly to the development of cancers in women depends on whether they can be formed in human tissues and the type of specific molecular and cellular responses they induce, if present. This review discusses the current data relating to these issues and highlights areas where further research is needed.
ISSN: 0267-8357
Type: Article
Description: This paper was published as Mutagenesis, 2009, 24 (5), pp. 391-404. It is available from or from the journal website at DOI: 10.1093/mutage/gep022
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Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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