Further Development 23.7: BPA and Cancer Susceptibility

Development in Health and Disease: Birth Defects, Endocrine Disruptors, and Cancer

Experimental studies in rodents suggest that in utero exposure to BPA may predispose women to breast cancer later in life. Fetal mammary glands from BPA-exposed mice displayed many developmental alterations, including altered extracellular matrices, earlier differentiation of adipocytes (fat cells), increased epithelial area, and smaller lumens, as well as extensive changes in the stromal and epithelial transcriptomes (Wadia et al. 2013). Moreover, exposure of female monkey fetuses to low (and environmentally relevant) doses of BPA caused changes in mammary development comparable to those seen in BPA-exposed mice (Figure 1). In rats, fetal exposure to BPA, followed at puberty by a “subcarcinogenic dose” of a chemical carcinogen, resulted in the formation of tumors only in those animals that had been first exposed to BPA as fetuses (Durando et al. 2007). In the above experiments, BPA was shown to be a factor that predisposed the rats to develop a cancer when they encountered chemical carcinogens later in life. In other rat studies, fetal exposure to low BPA levels caused the development of early-stage cancer in the mammary glands of one-third of the rats later in life (Murray et al. 2006). None of the control rats developed such cancers. Additionally, studies with a different strain of rats have shown that when rat embryos are exposed to BPA (at levels considered safe by the U.S. EPA), they can develop palpable postnatal tumors without having exposure to a chemical carcinogen or a second BPA experience later in life. Acevedo and colleagues (2013) conclude that “BPA may act as a complete mammary gland carcinogen.”

Figure 1 Bisphenol A induces altered mammary gland development. (A,B) Whole mount stained preparation of mammary glands from newborn female rhesus monkeys. (A) Control mammary gland. (B) Mammary gland from a fetus exposed in utero to BPA. Twice as many buds (incipient branches) are seen in the BPA-exposed tissue. (C) The percentage of mouse mammary glands showing intraductal hyperplasia (a cancer-prone state) is significantly increased at postnatal day (PND) 50 in BPA-exposed animals. (A and B from A. P. Tharp et al. 2012. Proc Natl Acad Sci USA 109: 8190-8195; C after T. J. Murray et al. 2007. Reprod Toxicol 23: 383–390.)

Literature Cited

Acevedo, N., B. Davis, C. M. Schaeberle, C. Sonnenschein and A. M. Soto. 2013. Perinatally administered bisphenol A as a potential mammary gland carcinogen in rats. Environ. Health Perspect. 121: 1040–1046.
PubMed Link

Durando, M., L. Kass, J. Piva, C. Sonnenschein, A. M. Soto, E. H. Luque and M. Muñoz-de-Toro. 2007. Prenatal bisphenol A exposure induces preneoplastic lesions in the mammary gland in Wistar rats. Environ. Health Perspect. 115: 80–86.
PubMed Link

Murray, T. J., M. V. Maffini, A. A. Ucci, C. Sonnenschein and A. M. Soto. 2006. Induction of mammary gland ductal hyperplasias and carcinoma in situ following fetal bisphenol A exposure. Reprod. Toxicol. 23: 383–390.
PubMed Link

Tharp, A.P., M. V. Maffini, P. A. Hunt, C. A. VandeVoort, C. Sonnenschein and A. M. Soto. 2012. Bisphenol A alters the development of the rhesus monkey mammary gland. Proc. Natl. Acad. Sci. USA 109: 8190–8195.
PubMed Link

Wadia, P. R., N. J. Cabaton, M. D. Borrero, B. S. Rubin, C. Sonnenschein, T. Shioda and A. M. Soto. 2013. Low-dose BPA exposure alters the mesenchymal and epithelial transcriptomes of the mouse fetal mammary gland. PLOS ONE 8: e63902.

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