Oral exposure to bisphenol a increases dimethylbenzanthracene-induced mammary cancer in rats.
BACKGROUND
Bisphenol A (BPA) is widely used in the manufacture of polycarbonate plastics, including infant formula bottles.


OBJECTIVE
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 mug 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.


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
S
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Raghuraman
Nandini
N
Eltoum
Isam
I
Carpenter
Mark
M
Russo
Jose
J
Lamartiniere
Coral A
CA
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D001559:Benzhydryl Compounds; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D007774:Lactation; D008321:Mammary Glands, Animal / Q000187:drug effects*; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced*; D018811:Maternal Exposure / Q000009:adverse effects; D010636:Phenols / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000098826:Bisphenol A Compounds
D015127:9,10-Dimethyl-1,2-benzanthracene; D001559:Benzhydryl Compounds; D002273:Carcinogens; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds