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Plastic Tied to Chromosome Damage in Mice

Study on chemical could be an insight into birth defects

MONDAY, March 31, 2003 (HealthDayNews) -- The inadvertent use of the wrong detergent in a Cleveland laboratory has led scientists to serendipitous insights on what may be behind many cases of mental retardation and birth defects in humans.

In this purely coincidental scenario, the detergent apparently damaged the plastic cages, causing them to leach bisphenol A (BPA), a compound that has hormone-like properties. This in turn appears to have led to chromosomal abnormalities in the mice. Although this was an extreme circumstance, scientists have since shown that even normal wear-and-tear to common plastic items can cause the same problem.

While not discounting the results of the research, a spokesman for the plastics industry says the research is incomplete and the compound has been safe in people.

A few years ago, Patricia Hunt, a geneticist at Case Western Reserve University in Cleveland, was conducting an experiment to see if hormone changes in women during their last decade of reproductive life resulted in aneuploidy, or an abnormal number of chromosomes in the egg.

An estimated 10 percent to 25 percent of fertilized human eggs are aneuploid, or have an abnormal number of chromosomes. Aneuploidy is consequently the leading cause of mental retardation and birth defects in humans, including Down syndrome.

Hunt's study was going well and producing the results she wanted when, almost overnight, the rate of chromosomal abnormalities in the control mice jumped from under 2 percent to 40 percent.

Researchers conducting an unrelated experiment in a different lab in the same department reported the same thing at exactly the same time.

Hunt initially thought it was the animals themselves, or perhaps an environmental cue coming in through an air duct. Then she and her colleagues noticed the mouse cages were deteriorating. "They were going from clear plastic to hazy, then some stress cracks appeared, then they got bubbly and sticky and really nasty," she recalls. This happened over a period of many weeks, even after the cages were repeatedly washed with normal detergent.

A little detective work revealed that a temporary building worker had used the wrong detergent to wash the mouse cages. That detergent had apparently damaged the plastic, causing BPA to leach from the polycarbonate material used to make the cages and water bottles.

BPA is used widely by the plastics industry to make common plastic food and beverage containers as well as baby bottles. Although it is manmade, BPA has been shown to mimic the effects of estrogen. Its effect on reproduction is controversial, Hunt says.

Hunt decided to take another, methodical look at the problem and discovered that extremely low levels of BPA -- daily doses of 20 parts per billion over five to seven days -- interfered with the cell division in the eggs of female mice. This study, which is reported in the April 1 issue of Current Biology, is the first time scientists have shown that environmental exposure to BPA affects the eggs in such a way.

A looming, unanswered question, of course, is whether environmental exposure to BPA can cause the same problem in humans. "It's always hard to know how to extrapolate to humans," Hunt says. "We use the mouse under the assumption that the basic process of cell division is really well conserved between mammals and, for the most part, that's true. If it's true for something like this, we have no way of knowing."

While an extra-strong detergent caused the mouse cages to leach quickly and dramatically, normal wear and tear can have the same effect over time, Hunt says. "It just depends on what levels are sufficient to do bad things, and we don't really have any idea," she says. One concern is the levels that caused harm to mice are within the realm of what humans are normally exposed to.

"The more I read, the more I'm concerned that there are some significant reproductive effects of this and they have been dismissed," Hunt says. The effects being seen here are different than in the past. "Unlike previously reported effects that lead to alterations in the reproductive tract, the effect we are reporting would influence the next generation."

"Nobody really knows how to interpret these results," says Steven Hentges, executive director of the polycarbonate business unit of the American Plastics Council. "It's only an indicator that more research is needed to see if the technique is valuable. She also makes a point that the relevance to humans isn't known that ties into the technique she's using -- whether it really has predictive value, is it repeatable."

While Hunt and her colleagues looked at chromosomal abnormalities, they did not actually look at whether the mice had reproductive or birth defects, Hentges says.

A number of previous studies essentially absolved BPA of harmful effects in these areas. "If you look at that full weight of evidence, studies that actually look at health outcomes, reproductive success or congenital defects or any other kind of developmental issues, you don't actually find them," Hentges says.

More information

For more information on bisphenol A (BPA), visit the American Plastics Council. For a more critical look at the possible effects of BPA on humans, go to Our Stolen Future.

SOURCES: Patricia Hunt, Ph.D., associate professor, department of genetics, Case Western Reserve University School of Medicine, Cleveland; Steven Hentges, Ph.D., executive director, polycarbonate business unit, American Plastics Council, Arlington, Va.; April 1, 2003, Current Biology
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