In an article published on November 2, 2018, in the peer-reviewed journal Environmental Health Perspectives, Gail Prins and colleagues from the Department of Urology, University of Illinois at Chicago, U.S., reported on the effects of bisphenol A (BPA, CAS 80-05-7) exposure on prostate cancer risk. Developmental exposures of male rats to 2.5-25,000 µg/kg-bw by oral gavage were performed within the CLARITY-BPA consortium, a big study combining the established regulatory testing procedures with investigative approaches currently used by academic scientists (FPF reported).
The research by Prins and colleagues builds on an earlier work that “determined that early life exposure to low-dose BPA increased rat prostate cancer risk” (FPF reported). The specific goal of the current study was to “reassess whether a range of BPA exposures drives prostate pathology and/or alters prostatic susceptibility to hormonal carcinogenesis.” To study the latter, one group of BPA-exposed rats was additionally “given testosterone plus estradiol (T+E) implants at day 90 to promote carcinogenesis with aging.” Rats exposed to BPA alone did not show any prostate pathology. However, BPA-exposed animals had a “greater severity of lateral prostate intraepithelial neoplasia” when they were subjected to hormonal carcinogenesis. The researchers also observed various effects caused by different BPA doses in the “epithelial stem and progenitor cells” isolated from the prostates of BPA-exposed rats.
The authors concluded that their results “confirm and extend previous evidence using a rat model and human prostate epithelial cells that low-dose BPA augments cancer susceptibility and alters adult prostate stem cell homeostasis.” They “propose that BPA exposures may contribute to the increased carcinogenic risk in humans that occurs with aging.”
Prins, G.S., et al. (2018). “Evaluation of bisphenol A (BPA) exposures on prostate stem cell homeostasis and prostate cancer risk in the NCTR-Sprague-Dawley rat: An NIEHS/FDA CLARITY-BPA consortium study.” Environmental Health Perspectives 126:117001.
Prins, G.S., et al. (2017). “Prostate cancer risk and DNA methylation signatures in aging rats following developmental BPA exposure: A dose-response analysis.” Environmental Health Perspectives 125:077007.
Cheong, A., et al. (2016). “DNA methylome changes by estradiol benzoate and bisphenol A links early-life environmental exposures to prostate cancer risk.” Epigenetics 11:674-689.
Wong, R.L.Y., et al. (2015). “Identification of Secretaglobin Scgb2a1 as a target for developmental reprogramming by BPA in the rat prostate.” Epigenetics 10:127-134.
Prins, G.S., et al. (2014). “Bisphenol A promotes human prostate stem-progenitor self-renewal and increases in vivo carcinogenesis in human prostate epithelium.” Endocrinology 155:805-817.
Tang, W., et al. (2012). “Neonatal exposure to estradiol/bisphenol A alters promoter methylation and expression of Nsbp1 and Hpcal1 genes and transcriptional programs of Dnmt3a/b and Mbd2/4 in the rat prostate gland throughout life.” Endocrinology 153:42-55.
Prins, G.S., et al. (2011). “Serum bisphenol A pharmacokinetics and prostate neoplastic responses following oral and subcutaneous exposures in neonatal Sprague-Dawley rats.” Reproductive Toxicology 31:1-9.
Ho, S.-M., et al. (2006). “Developmental exposure to estradiol and bisphenol A increases susceptibility to prostate carcinogenesis and epigenetically regulates phosphodiesterase type 4 variant.” Cancer Research 66:5624-5632.