Neonatal Estrogen Exposure Leads to Prostate Cancer in Rats

CHICAGO, June 1 ? It's a complicated trail twixt man and rats, but neonatal environmental estrogen exposure in the rodents appears to predispose them to prostate cancer as adults.

The finding is the first clear evidence that, for rats, exposure of the prostate during development to low doses of estrogen-like substances in the environment has long-term effects on cancer risk, according to Gail Prins, Ph.D., of the University of Illinois at Chicago.

In the June 1 issue of Cancer Research, Dr. Prins and colleagues also reported that exposure to estrogens in rats causes permanent alterations in the DNA methylation patterns of several cell signaling genes, suggesting a mechanism that may explain the later predisposition, or at the least serve as a marker for risk.

While the implication is that similar effects might be seen in humans, the researchers cautioned that more study is needed. "These findings are true for an animal model, and application to human prostate disease will await future studies," they said.

The study compared the effects of neonatal administration of a corn-oil placebo to high-dose estradiol, low-dose estradiol, and an "environmentally relevant" dose of bisphenol A (BPA), an estrogenic compound used in the manufacture of plastics. Unlike humans, the key period for development of the prostate in rats is shortly after birth, rather than in the second and third trimester of pregnancy.

The researchers noted that BPA is found in human serum, with higher concentrations in placental and fetal tissue.

In the study, both doses of estradiol led to an increased incidence of prostatic intraepithelial neoplasia, but BPA did not, the researchers found.

However, when the rats reached adult age and were exposed to a mixture of estradiol and testosterone (intended to mimic the hormonal changes that naturally occur in the aging male), all three estrogenic compounds led to an increased incidence of prostatic intraepithelial neoplasia, the researchers said.

Specifically:

• In the control rats, adult testosterone and estradiol exposure increased the incidence of prostatic intraepithelial neoplasia to 40%.
• Low-dose early estradiol, followed by testosterone and estradiol, did not increase prostatic intraepithelial neoplasia lesions more than the testosterone and estradiol combination or neonatal low-estradiol exposures alone.
• However, early exposure to high-dose estradiol followed by testosterone and estradiol further increased prostatic intraepithelial neoplasia incidence, to 100%.
• And strikingly, neonatal exposure to low-dose BPA, followed by adult exposure to testosterone and estradiol, also increased prostatic intraepithelial neoplasia incidence to 100%. The difference, compared to controls, was statistically significant at P