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Jenkins S , Raghuraman N , Eltoum I , Carpenter M , Russo J , Lamartiniere CA
Oral Exposure to Bisphenol A Increases Dimethylbenzanthracene-Induced Mammary Cancer in Rats
Environmental Health Perspectives. 2009 Jun;117(6) :910-915
PMCID: PMC2702405   
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BACKGROUND: Bisphenol A (BPA) is widely used in the manufacture of polycarbonate plastics, including infant formula bottles. OBJECTIVES: Based 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. METHODS: We exposed neonatal/prepubertal rats to BPA via lactation from nursing dams treated orally with 0, 25, and 250 mu g BPA/kg body weight/day. For turmorigenesis studies, female offspring were exposed to 30 mg dimethylbenzanthracene (DMBA)/kg body weight at 50 days of age. RESULTS: The 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. CONCLUSIONS: The 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.
Jenkins, Sarah Raghuraman, Nandini Eltoum, Isam Carpenter, Mark Russo, Jose Lamartiniere, Coral A. US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE 451HZ