Oral Exposure to Bisphenol A Increases Dimethylbenzanthracene-Induced Mammary Cancer in Rats

Abstract

BackgroundBisphenol A (BPA) is widely used in the manufacture of polycarbonate plastics, including infant formula bottles.ObjectivesBased on the reported endocrine disruptor activity of this polyphenol, we hypothesized that exposure to BPA early in life would elicit developmental changes in the mammary tissue and cause a predisposition for mammary cancer.MethodsWe exposed neonatal/prepubertal rats to BPA via lactation from nursing dams treated orally with 0, 25, and 250 μg BPA/kg body weight/day. For tumorigenesis studies, female offspring were exposed to 30 mg dimethylbenzanthracene (DMBA)/kg body weight at 50 days of age.ResultsThe combination of DMBA treatment with lactational exposure to BPA demonstrated a dose-dependent increase in mammary tumor multiplicity and reduced tumor latency compared with controls. In the absence of DMBA treatment, lactational BPA exposure resulted in increased cell proliferation and decreased apoptosis at 50 but not 21 days postpartum (shortly after last BPA treatment). Using Western blot analysis, we determined that steroid receptor coactivators (SRCs) 1–3, Akt, phosphorylated Akt, progesterone receptor A (PR-A), and erbB3 proteins were significantly up-regulated at 50 days of age.ConclusionsThe data presented here provide the first evidence that maternal exposure to BPA during lactation increases mammary carcinogenesis in a DMBA-induced model of rodent mammary cancer. Changes in PR-A, SRC 1–3, erbB3, and Akt activity are consistent with increased cell proliferation and decreased apoptosis playing a role in mammary cancer susceptibility. These alterations provide an explanation of enhanced mammary carcinogenesis after lactational BPA exposure.

Low dose effects of bisphenol A

“…4B). [137][138][139]250 The consistency of these results across laboratories is indicative of a highly reproducible low dose effect and provides strong evidence for adverse effects of BPA on this organ. Example 5: Low dose effects of BPA on the ovary Oogenesis begins in the fetal ovary with the entry of germ cells into meiosis and the subsequent formation of follicles (an oocyte surrounded by somatic cells).…”

“…[137][138][139] Another recent study revealed the presence of carcinomas in the mammary glands of rats exposed to low doses of BPA only during early development in the absence of any additional carcinogen treatment, providing further evidence that the mammary gland is affected by BPA. 140 A recent weight-ofevidence analysis found strong support for low dose effects and high levels of consistency between studies for both endpoints; 5 low doses were found to alter mammary gland morphology at many life stages, and numerous studies reported that low doses increase the incidence of preneoplastic and neoplastic lesions, as well as increase the response to chemical carcinogens.…”

Bisphenol A alters the development of the rhesus monkey mammary gland

“…Furthermore, rats exposed to BPA in utero developed precancerous and cancerous lesions (32). Also, perinatal exposure increased rodents' sensitivity to chemical carcinogens (33)(34)(35)(36). Although a small human study found no association between To whom correspondence should be addressed.…”

Impact of Environmental Contaminants on Breast Cancer / Wpływ Zanieczyszczenia Środowiska Na Raka Piersi

“…Moreover, developmental exposure to environmentally relevant levels of BPA during gestation and lactation induced mammary gland neoplasms in rats in the absence of any additional carcinogenic treatment indicating that BPA may act as a complete mammary gland carcinogen [137]. On the other hand, in rats maternal exposure to BPA during lactation was found to increase DMBA-induced mammary carcinogenesis in female offspring [138].…”