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dc.contributor.authorPrins, Gail S.
dc.contributor.authorTang, Wan-Yee
dc.contributor.authorBelmonte, Jessica
dc.contributor.authorHo, Shuk-Mei
dc.date.accessioned2009-08-08T16:01:34Z
dc.date.available2009-08-08T16:01:34Z
dc.date.issued2008-01
dc.identifier.bibliographicCitationGail S. Prins, Wan-Yee Tang, Jessica Belmonte, Shuk-Mei Ho (2008) Perinatal Exposure to Oestradiol and Bisphenol A Alters the Prostate Epigenome and Increases Susceptibility to Carcinogenesis Basic & Clinical Pharmacology & Toxicology 102 (2) , 134–138en
dc.identifier.issn1742-7843
dc.identifier.otherdoi:10.1111/j.1742-7843.2007.00166.x
dc.identifier.urihttp://hdl.handle.net/10027/6205
dc.descriptionThe definitive version is available at www.blackwell-synergy.com. Publisher's copyright: http://www.blackwell-synergy.com/help?context=terms_and_conditionsen
dc.description.abstractAn important and controversial health concern is whether low-dose exposures to hormonally active environmental oestrogens such as bisphenol A can promote human diseases including prostate cancer. Our studies in rats have shown that pharmacological doses of oestradiol administered during the critical window of prostate development result in marked prostate pathology in adulthood that progress to neoplastic lesions with ageing. Our recent studies have also demonstrated that transient developmental exposure of rats to low, environmentally relevant doses of bisphenol A or oestradiol increases prostate gland susceptibility to adult-onset precancerous lesions and hormonal carcinogenesis. These findings indicate that a wide range of oestrogenic exposures during development can predispose to prostatic neoplasia that suggests a potential developmental basis for this adult disease. To identify a molecular basis for oestrogen imprinting, we screened for DNA methylation changes over time in the exposed prostate glands. We found permanent alterations in DNA methylation patterns of multiple cell signalling genes suggesting an epigenetic mechanism of action. For phosphodiesterase type 4 variant 4 (PDE4D4), an enzyme responsible for intracellular cyclic adenosine monophosphate breakdown, a specific methylation cluster was identified in the 5'-flanking CpG island that was gradually hypermethylated with ageing in normal prostates resulting in loss of gene expression. However, in prostates exposed to neonatal oestradiol or bisphenol A, this region became hypomethylated with ageing resulting in persistent and elevated PDE4D4 expression. In total, these findings indicate that low-dose exposures to ubiquitous environmental oestrogens impact the prostate epigenome during development and in so doing, promote prostate disease with ageing.en
dc.language.isoen_USen
dc.publisherBlackwell Synergyen
dc.subjectdisease susceptibilityen
dc.subjectestradiolen
dc.titlePerinatal exposure to estradiol and bisphenol A alters the prostate epigenome and increases susceptibility to carcinogenesisen
dc.title.alternativePerinatal exposure to oestradiol and bisphenol A alters the prostate epigenome and increases susceptibility to carcinogenesisen
dc.typeArticleen


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