Plastics Chemical Might Promote Breast Cancer

Scientists spot mechanism allowing bisphenol-A to concentrate in tumor cells

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By E.J. Mundell
HealthDay Reporter

FRIDAY, Aug. 25, 2006 (HealthDay News) -- A chemical found in the harder plastics that make up CD cases, water-cooler jugs and other objects people handle might help promote breast cancer, researchers say.

The chemical -- a "pseudo-estrogen" called bisphenol-A -- appears to be preferentially absorbed by breast tumor cells, according to a new study published in the Aug. 28 issue of Chemistry & Biology.

While the new research doesn't give any definitive answer on BPA's potential role in breast cancer, American researchers say they have uncovered a biological mechanism that allows the compound to concentrate in tumor cells.

Healthy cells don't readily absorb bisphenol sulfate, one of the body's metabolized forms of BPA. So, many experts have assumed the chemical might be harmless.

However, "it turns out that breast tumor cells are different than normal cells," lead researcher Theodore Widlanski of Indiana University, said. "We showed that breast tumor cells actually convert bisphenol sulfate back into bisphenol-A, which can then be taken up into tumor cells."

"These guys were aiming at what I'd say was the 'missing link,'" added Patricia Hunt, a molecular bioscience professor at Washington State University who has conducted her own studies suggesting a link between BPA and birth defects in mice. "This is a first step, and a really important first step," she said.

The effects of BPA on human health -- if any -- have been hotly debated. Previous studies have linked even small exposures to prostate abnormalities in mice that suggest -- but do not prove -- a link between the plastics chemical and human prostate cancer.

Other studies, including Hunt's, have theorized that embryonic and fetal exposures to BPA might trigger chromosomal changes that, in turn, could raise risks for mental retardation and birth defects.

BPA is a raw material used in the manufacture of hard, clear plastic products -- everything from electronics parts to food-storage containers and baby bottles. It is not found in softer, more flexible products such as single-serving water bottles.

The chemical is known a "pseudo-estrogen" because it is one of a number of natural or synthetic materials that can be taken into human cells and trigger estrogenic effects. But unlike estrogen, BPA undergoes chemical modifications as it enters the body, which makes its absorption by healthy human cells nearly impossible.

Specifically, the addition of a sulfate molecule to BPA keeps it from permeating the healthy cell's outer membrane. But would the same phenomenon hold true for malignant cells, researchers wondered?

In a laboratory study using human breast cancer cell lines, the Indiana researchers, along with scientists from the University of California at Berkley, found that BPA appeared to concentrate in tumor cells.

"We found no BPA in the medium the cells were grown in," Widlanski noted.

The key, according to Widlanski, is that the breast tumor cell carries an enzyme on its surface that strips sulfate molecules away from BPA. "Healthy cells don't have this property," he said. Once inside the tumor cell, BPA might encourage the cell's survival and proliferation, in the same way that estrogen does.

Widlanski cautioned, however, that his team's study had only uncovered a potential mechanism linking BPA to the promotion of breast cancer. Whether this mechanism actually occurs in real life is tough to prove, he said, as is the notion that BPA exposure plays a significant role in breast cancer.

The bottom line, according to Widlanski: "If you weren't alarmed yesterday about BPA, then you shouldn't be alarmed today. Nothing we have shown changes the innate danger. We have just reported a mechanism."

The plastics industry strongly defended its products.

"BPA has been extensively studied for its potential to cause cancer, including lifetime studies in rats and mice," said Steven Hentges, executive director of the Polycarbonate Business Unit at the American Plastics Council, which represents the industry.

He added that governments around the world have also commissioned their own studies on BPA, "and, in every case, have concluded that BPA is not likely to pose a carcinogenic risk to humans."

Hentges said the study also has serious flaws.

"First of all, it's an in vitro study," he said. "You can't extrapolate from a cell culture and say much of anything about breast cancer." And, he said, tests conducted recently by the U.S. Centers for Disease Control and Prevention (CDC) found average levels of BPA in human urine to be infinitesimally small -- about one part per billion.

Widlanski agreed that short-term, in vitro studies can never fully explain human disease. He also agreed that urine and blood concentrations of BPA metabolites in humans are much, much smaller than exposures used in this study.

"Unfortunately, we simply can't mimic long-term exposure to bisphenol A," he said, since it's unethical to give human test volunteers any chemical with an unproven safety record, especially over the long term.

"So, we have to use a larger concentration to mimic the effects of long-term exposure," he said. "No one knows if that's a valid way to do that or not." Animal studies are a logical next step, he said, but they can never fully replicate potential effects in humans.

"The real crux of the matter is that we are surrounded in our environment by chemicals that are pseudo-estrogenic, not just BPA," Widlanski added. "It's the cumulative effect of all of these compounds together that one needs to worry about."

Hunt said the new study does provide "badly needed mechanistic data" on a suspect compound.

"There's a body of data that's out there suggesting [BPA] exerts a pretty powerful effect on a number of different tissues," she said. "There have been studies of the developing embryo, and studies looking at the development of prostate tissue. This provides a way of understanding how this chemical may exert its effect."

More information

For more on breast cancer, head to the American Cancer Society.

SOURCES: Patricia Hunt, Ph.D., Meyer Distinguished Professor, School of Molecular Biosciences, Washington State University, Seattle; Steven Hentges, Ph.D., executive director, Polycarbonate Business Unit, American Plastics Council; Theodore Widlanski, Ph.D., professor, chemistry, Indiana University, Bloomington; Aug. 28, 2006, Chemistry & Biology

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