Low-dose BPA exposure increased prostate cancer risk in stem cells

SAN FRANCISCO — In vivo evidence shows that developmental exposure to bisphenol A significantly increases the carcinogenic susceptibility of the human prostate epithelium, according to data presented here at ENDO13.

“Our new findings provide the first direct in vivo evidence that early life exposure to BPA [bisphenol A] at levels found every day in humans increases cancer susceptibility in the human prostate epithelium,” Gail S. Prins, PhD, Michael Reese professor of urology in the departments of urology and physiology and biophysics at the University of Illinois at Chicago, said during a press conference here.

In a rodent study published in 2007, Prins and colleagues demonstrated that brief exposure to low doses of BPA early in life reprogrammed the prostate gland and enhanced the carcinogenic potential when exposed to elevated adult estrogen levels, as seen in aging men.

In the current study, Prins and colleagues tested the effects of BPA in an in vivo chimeric prostate model of human prostate epithelial stem-progenitor cells cultured from primary prostate epithelial cells of healthy donors.

They exposed host mice to daily oral low doses of BPA (100 mcg/kg of body weight [BW], n=15; 250 mcg/kg of body weight [BW], n=27) or vehicle (n=34) during the first 2 weeks of tissue formation in vivo.

At day 7, serum BPA levels were 0.16 ng/mL free-BPA and 0.47 ng/mL free-BPA for the 100 mcg/kg BW and 250 mcg/kg BW groups, respectively.

One month after the graft, mice were administered testosterone plus estradiol (T+E) pellets and researchers monitored carcinogensis over a 4-month period.

Among controls with T+E alone, the incidence rate for high grade prostate intraepithelial neoplasia and prostate adenocarcinoma was 12%; 26% of grafts demonstrated normal histology.

During tissue development, treatment with either BPA dose significantly increased intraepithelial neoplasia and prostate adenocarcinoma, with an incidence of 33% (P<.05); the remainder had benign lesions with no grafts demonstrating normal histology.

An additional group (n=42) was given 200 nM BPA during prostasphere culture, followed by 250 mcg/kg BW in vivo during tissue formation to model continuous developmental exposure. Among this group, incidence of intraepithelial neoplasia and prostate adenocarcinoma increased to 45% (P<.01).

For more information:

Prins G. #OR38-1. Presented at: The Endocrine Society Annual Meeting and Expo; June 15-18, 2013; San Francisco.