4 April 2003
Accident Reveals Potential Health Risks of Common Compound
August 1998, geneticist Patricia Hunt noticed a bizarre change in
the eggs of the female mice she was studying. For some inexplicable
reason, the chromosomes in 40% of the eggs looked abnormal--a wild
jump from the 1% to 2% abnormality her lab typically observes. Something
seemed to have gone terribly wrong with meiosis, the process that
separates chromosomes during reproduction so that when egg and sperm
come together, they each contribute half the genetic material to
an embryo. Hunt, whose lab at Case Western Reserve University in
Cleveland, Ohio, specializes in problems with meiosis--which in
humans causes more birth defects, mental retardation, and miscarriage
than any other factor--had her lab workers redo the study twice,
yielding the same baffling results each time.
mess. Chromosomes (red) should neatly line up on spindle (green),
but BPA wreaks havoc (bottom) in mouse eggs.
P. A. HUNT ET AL., CURRENT BIOLOGY 13, 546 (2003)
first clue came that fall, when Hunt noticed that her mouse cages,
made of a plastic called polycarbonate, appeared to be melting.
She found that a lab worker had mistakenly washed the cages with
a highly alkaline detergent. "He was a temporary worker who
made a lasting impression," Hunt says. Hunt, Terry Hassold,
and their colleagues eventually pinned the meiotic abnormalities
on a chemical called bisphenol A (BPA) leaching from the damaged
plastic. Although several labs have shown that BPA, a compound widely
used in plastics manufacturing, can disrupt the reproductive system
of rodents, none had previously shown an effect on meiosis.
detective work, described in a paper in the 1 April issue of Current
Biology, has thrust Hunt's lab into the middle of the controversial
field of endocrine disrupters. Some researchers and environmentalists
have argued that low levels of certain synthetic chemicals in the
environment are causing reproductive problems in wildlife and perhaps
humans. BPA, which weakly mimics the effects of estrogen has been
among the suspects.
from diverse disciplines say the work deserves serious attention.
"It's fascinating," says Charles Epstein, a developmental
biologist at the University of California, San Francisco, who studies
chromosomal imbalances in mice. Even Stephen Safe of Texas A&M
University in College Station, a leading skeptic of evidence linking
endocrine disruptors to health problems, says, "I think their
data are very interesting." Leading proponents of BPA's harmful
effects predictably have stronger words: "I look at this as
a watershed paper," says reproductive biologist Frederick vom
Saal of the University of Missouri, Columbia, whose lab has published
several studies of BPA's impact on mouse reproductive development.
and co-workers first noticed problems when they took a routine "snapshot"
of the meiotic process in their mice. They found that 40% of the
mouse eggs failed to assemble their chromosomes neatly on the spindle
apparatus, a step that must occur for separation to take place properly.
They also found abnormal numbers of chromosomes, an aberration called
aneuploidy, in about 12% of the eggs. "When I read that I said,
'Zowee, that's really out of sight,' " says John Eppig, a reproduction
biologist at the Jackson Laboratory in Bar Harbor, Maine.
they suspected BPA, Hunt and co-workers recreated the accident.
They intentionally damaged polycarbonate cages and water bottles
with detergent and compared the mice in those cages with animals
kept in undamaged cages with glass bottles. They found the same
levels of meiotic error in the mice kept in the damaged cages. They
then showed that BPA was the culprit by adding the chemical to mouse
water; it caused chromosomal problems, though not as severe. "It's
probably the only convincing demonstration of an environmental effect
on the frequency of aneuploidy," says Dorothy Warburton, a
cytogeneticist at Columbia University in New York City who has studied
aneuploidy extensively. "It's a little scary."
Hunt stresses that no data clearly link BPA to human aneuploidy,
she thinks the question deserves study because the compound is so
widely used: Plastics that contain it are made into baby bottles,
the liners of food cans, dental sealants, and many other common
products. More immediately, she says her finding should cause researchers
to consider retiring their polycarbonate cages, which naturally
degrade over time. And for her own research, this serendipitous
finding provides a powerful new tool to create and study aneuploidy