Exposure to low levels of bisphenol A during development may make men more susceptible to prostate cancer later in life, according to a new study published Tuesday.
The study, which uses a new model of implanting human stem cells into mice, is the first to link early-life BPA exposure to human prostate cancer. It adds to a growing body of research that suggests exposure to low doses of the chemical alters cells and can lead to diseases later in life.
"Overall I think this is some of the strongest and most convincing evidence to date linking early-life BPA exposure and cancer," said Heather Patisaul, a researcher at North Carolina State University who was not involved in the study. "They were careful to make the exposures human relevant, used cells derived from healthy humans and replicated physiological conditions seen in aging men."
Prostate cancer is the second leading cause of cancer-related death in U.S. men. About 15 percent of men will be diagnosed with prostate cancer in their lifetime, according to the National Cancer Institute.
BPA is used to make polycarbonate plastics and is found in in some paper receipts, liners of some food cans and dental sealants. More than 90 percent of Americans have traces in their bodies and previous studies suggest there is "universal fetal exposure."
Researchers led by a team from the University of Illinois at Chicago implanted prostate stem cells from deceased young men into mice. When the mice were fed BPA by mouth for the first two weeks of life, 33 percent of the stem cells had cancerous or precancerous lesions later in life. Forty-five percent of the cells that were exposed to BPA before and after mice implantation developed precancerous or cancerous lesions later. In comparison, only 12 percent of the mice not exposed to BPA during development had cancer or precancerous lesions later in life.
BPA acts as an estrogen and previous research has linked elevated estrogen levels during pregnancy to increased risk of prostate cancer in males.
"We know that stem cells help replenish our organs throughout life. We propose that if there is exposure early in life to an estrogenic compound – such as BPA – it reprograms our stem cells," said Gail Prins, a University of Illinois at Chicago researcher and lead author of the study, which was published in the journal Endocrinology.
Although the cells were from deceased adults, by using regenerative stem cells that produce prostate tissues, the researchers said they were able to simulate developmental exposure. It is the latest addition to a growing body of research – called epigenetics – that has linked some chemicals to altered DNA sequencing in fetuses that can lead to diseases later in life.
Patisaul said the new model cannot "perfectly replicate human physiology," but is advantageous because they're exploring "the impact of BPA ... on human cells in a whole animal instead of a dish."
Rising estrogen levels
However, a representative of the chemical industry said that the model of implanting the stem cells into mice has not been established to be valid. The study has "very limited relevance to real-life human exposures to BPA," Steve Hentges, a representative of the American Chemistry Council, said in a prepared statement.
"The [BPA] levels tested are more than 1,000 times higher than typical human exposures," he said.
Prins said "that's just not true."
"Twenty minutes after exposure the levels of BPA measured in the blood of the animals that were the hosts bearing the transplants were exactly what we're seeing measured in the umbilical cord fluid of women," Prins said, citing a 2013 study on California women.
In addition to the BPA, all the mice were given an estrogen to simulate human male aging. As men age their estrogen levels rise.
Men's rising levels of estrogen are at least partly responsible for prostate cancer. Prins said the early-life exposure to BPA is sensitizing the prostate stem cells to estrogen, and the stem cells pass along this estrogen sensitivity to prostate tissues later in life.
Prins' earlier work found that rats exposed to BPA at human-relevant doses had adult prostates that were more sensitive to developing cancer.
Also, developmental BPA exposure was linked to breast cancer in rats last year by Tufts University researchers, but the data did not reach statistical significance, said Nicole Acevedo, a postdoctoral researcher at Tufts University and lead author of the study. Some rats exposed to low doses of BPA developed malignant tumors while none of the non-exposed did. [Editor's Note 1/8: Changed to reflect it was some rats not all].