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A largely ignored contaminant doesn’t just resemble bisphenol A, thechemical found to leach out of hard plastic water bottles. It’s BPA’sfluorinated twin — on steroids.
New laboratory studies in Japanindicate that the twin, called bisphenol AF, or BPAF, may be even morepotent than BPA in altering the effects of steroid hormones such asestrogens in the body.
The unusual way that BPAF blocks someestrogen actions and fosters others “could make this a viciouscompound, a very toxic compound,” says Jan-Åke Gustafsson, a molecularendocrinologist at the University of Houston. The chemical is aningredient of many plastics, electronic devices, optical fibers andmore.
The last letter in bisphenol AF’s name denotes thesubstitution of fluorine atoms for six hydrogens and explains why thecompound is sometimes referred to as hexafluoro-BPA. These fluorinesalso make BPAF behave differently than BPA in the body, biochemistYasuyuki Shimohigashi of Kyushu University in Fukuoka, Japan, and hiscolleagues report online April 28 in Environmental Health Perspectives.
Bothchemicals act on estrogen receptors, molecular locks found in cellsthroughout the body. Estrogen hormones serve as their keys, turning ongenes that control time-sensitive activities such as ovulation in youngwomen. Certain contaminants, such as BPA and BPAF, can mimic those keys.
Butsome mimics are better than others and may even, like skeleton keys,act on a variety of locks. Most of BPA’s estrogen-mimicking effect,Shimohigashi’s group found in 2006, comes from activating a cellularswitch known as human estrogen-related receptor gamma, or ERR-gamma. It’s an “orphan” receptor, meaning a lock with no known natural key.
Inits latest study, the Japanese group performed tests in isolated cellsand receptor proteins. And BPAF, the researchers now report, all butignores ERR-gamma. Instead, the chemical’s fluorine atoms appear togive it a strong affinity for the two best-studied estrogen receptors,ER-alpha and ER-beta. Indeed, the fluorines bind to ER-alpha some 20time more effectively than BPA does, and to ER-beta almost 50 timesmore effectively.
After binding, BPAF proved a potent activatorof ER-alpha, unleashing its actions just as the body’s own estrogenwould. The big surprise, Shimohigashi says, was finding that despiteBPAF’s even stronger affinity for ER-beta, it elicited no activity fromthis lock. The chemical enters the receptor and then just sits therelike a dud. In so doing, it blocks the receptor’s access to the body’sown estrogen — preventing it from unlocking any of the myriadoperations normally controlled via this important receptor.
WhereER-alpha can promote reproductive cancers, actions triggered throughER-beta tend to inhibit cancer development and foster health in a rangeof tissues throughout the body. “So simplistically speaking,”Gustafsson says, “ER-alpha is the bad guy and ER-beta is the good one.”Generally, he says, their actions tend to balance one another.
Andthat’s what appears to make BPAF such a “double-edged sword,” hecontends. By increasing ER-alpha activity and shutting down ER-beta’scountervailing functions, BPAF appears to shift endocrine action towardgreater toxicity, he says.
Early hints of BPAF’s hormonal alterego prompted the National Toxicology Program in late 2008 to target itfor federal toxicity testing in rodents. Shimohigashi says his teamwill soon begin similar studies to investigate how the newly unveiledendocrine effects play out in whole animals.
Little is knownabout the quantity of BPAF produced each year or likely humanexposures. One federal study conducted nearly three decades agoestimated that some 4,400 U.S. workers likely encountered the chemicalat the time, according to a brief online report by the NationalToxicology Program. That report also notes that the contaminant hasbeen detected in women’s fat — a sign that it could, duringbreastfeeding, be passed along to a baby.
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Post time 17-5-2010 04:31 PM
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