SCIENCE & TECHNOLOGY cells. Methylmercury enters the kidney and the liver and avidly accumulates in growing hair. Hair is often used as a biological marker for mercury exposure. Methylmercury also crosses the bloodbrain barrier. Actually, it is carried across in an intriguing example of molecular mimicry Methylmercury easily complexes with free L-cysteine. A certain amino acid carrier, mistaking the complex for L-methioLOUISA WRAY DALTON, C&EN WASHINGTON nine, carries the mercury into the tightly packed endothelial cells that make up the blood-brain barrier. Inside the endothelial and forms "partly covalent/partly ionic UMANS ARE EXPOSED TO MORE cells, glutathione—a tripeptide made of bonds that are strong but reversible," says mercury from eating fish, macysteine, glutamic acid, and glycine—picks Thomas W Clarkson, professor of envirine mammals, and crustaceans up methylmercury (Glutathione is found ronmental medicine at the University of than from any other source, acin higher concentration inside the cell than Rochester. Clarkson emphasizes that cording to the Food & Drug Adfree cysteine.) "Glutathione can be methylmercury is not lipid-soluble like ministration and the Environmental Propumped out of the cell on a glutathione polychlorinated biphenyls (PCBs) and othtection Agency Last month, they issued a carrier," Clarkson says. "So this is a twoer organochlorine contaminants. Clarkson joint draft advisory about fish consumpstep transport system for the blood-brain writes in a review that "methylmercury is tion to women who are or might become barrier. [Mercury] goes into the cell on the present in the body as water-soluble compregnant, and they plan to issue a new genblood side as methylmercury-cysteine, and plexes mainly, if not exclusively, attached to eral consumer advisory in the coming it comes out into the extracellular fluid of the sulfur atom of thiol ligands" {Environ. months. According to the December adHealth Perspect, 110,11 (2002)]. And that the brain as methylmercury-glutathione." visory, nearly all fish contain at least traces Methylmercury easily crosses the plaoften means it follows protein pathways, of methylmercury, although the amount cental barrier as well, and the same twoas opposed to lipid pathways, in the body of mercury can vary considerably step transport likely occurs there. In fact, Last November, researchers reported an Methylmercury, a biologically active any cell that takes up L-methionine from X-ray absorption study in fish that revealed form of mercury, is derived from inorganthe extracellular matrix has a chance of methylmercury predominantly binds to ic mercury Elemental mercury vapor that cysteine thiols [Science, 301,1203 (2003)]. welcoming in methylmercury-cysteine occurs naturally in the environment and is instead. released by industrial plants is It is in the brain and central oxidized to Hg 2+ in the at- 1 nervous system where methylmosphere and returned to | mercury wreaks its greatest Earth's surface in rainwater. £ harm. Methylmercury's presInorganic mercury from both « ence leads to loss of nerve cells, natural and human sources is ° especially in pockets of the laid down in sediments in the ? cerebrum and cerebellum. The ocean and in bodies of fresh- 3 symptoms of mercury in water. Inorganic mercury is adults, Clarkson says, include converted to methylmercury numbness; difficulty in speakby aquatic bacteria. Plankton ing; and loss of coordination, take it up, fish eat the planksight, or hearing. ton, bigger fish eat the smaller fish, and methylmercury Yet how it damages nerve bioaccumulates up the food cells is still largely unknown. chain. According to Joy C. Some evidence suggests that Andrews, a professor of methylmercury may inhibit chemistry at California State protein synthesis in the brain, University, Hayward, the ac- QUICKSILVER This rendition of mercury's transformations Clarkson says. It is known that, cumulation can result in "mer- in the environment—from elemental (Hg°) to inorganic (Hg2+) in the brain, methylmercury cury levels 1 million times to methylmercury (MeHg)—was drawn by artist Helena King, demethylates slowly to inorhigher in fish than in the sur- wife of mercury researcher Clarkson. ganic mercury Inorganic merrounding waters. " ~~ cury builds up because it does not cross back through the blood-brain Why methylmercury accumulates so Yet because of its reversible binding, barrier. Whether inorganic mercury in the readily in living systems partly has to do methylmercury may not stay long with any brain contributes to mercury toxicity is an with its binding properties. "There is no one thiol, Clarkson says. It moves easily open question. methylmercury—unbound—once it gets throughout a system. Once inside the huinto an organism," says Rudolfs K. Zalups, man body, roughly 95% of fish-derived In addition, before the symptoms of toxprofessor of medicine at Mercer Universimethylmercury is absorbed from the gasicity set in, almost every victim of mercuty School of Medicine, Atlanta. In partictrointestinal tract and distributed widely ry poisoning goes through a symptomless ular, methylmercury commonly binds to About 1 to 10% can be found in the blood, latent period that can last from weeks to thiol groups. Methylmercury is a cation mostly bound to hemoglobin in red blood months. Scientists can't explain it, and
METHYLMERCURY TOXICOLOGY PROBED
Seafood contaminant moves through the body, often posturing as benign molecule
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Clarkson calls it one of the greatest mysteries of mercury toxicity One well-documented case of mercury poisoning involved a chemistry professor, Karen E. Wetterhahn, at Dartmouth College. She spilled a few drops of highly toxic dimethylmercury on her gloved hand in August, and her highest exposure level, according to testing of hair samples, was in August. Yet not until December did the symptoms of mercury toxicity appear. This latent time span is unpredictable and does not seem to be dependent on dose, Clarkson says. "It is as if it triggers somethingsome process that takes its own time," he adds. The extent to which methylmercury leaves the body plays a role in its toxicity Methylmercuiys exit from the body takes advantage of natural transport mechanisms. Only a small proportion of methylmercury leaves the body in urine because the kidney reabsorbs it. "Yet methylmercury that gets into liver cells is pumped out into the bile as methylmercury-glutathione, according to studies conducted by Ned Ballatori at the University of Rochester. As it passes down the biliary
tract, some of it converts back to methylmercury-cysteine and is reabsorbed. But some is also converted by the natural microflora in the gut to inorganic mercury, which is excreted, according to Ian Rowland, a professor at the University of Ulster, in Northern Ireland. Each day, an adult body releases about 1% of its total methylmercury burden. METHYLMERCURY'S continual release from the body means that a consistent, low dose of methylmercury, as long as it is under a certain threshold, does not build up to a toxic dose. For babies, the story is different. Studies in suckling rats and monkeys indicate that nursing infants may not be able to get rid of methylmercury in the same way because their microflora are not yet able to break down methylmercury. Indeed, whether infants even have a mechanism for removing methylmercury from the body is a major research question. In addition, the infant brain sustains a different, more extensive type of damage from mercury poisoning. In 1971-72, scientists had the opportunity to observe
many of the effects of mercury poisoning in both infants and adults when as many as 40,000 individuals in Iraq ate bread made from wheat treated with methylmercury as a fungicide. In children's brains, two major changes were observed: The cells appeared to stop dividing and migrating. Both of these changes caused widespread damage in the infant brains—unlike the pockets of damage observed in adult brains. Both cell division and cell migration depend on the microtubular system, Clarkson says. And methylmercury either destroys microtubules or blocks their assembly. "People argue that's why the developing brain is so sensitive to methylmercury," Clarkson says. Researchers don't yet know how methylmercury exerts these effects, but they expect that the sulfhydryl group on tubulin proteins may play a role. Especially in a developing body, methylmercury is an insidious toxicant. It masquerades so well as a useful biological molecule that the body accepts it and allows it to go where other foreign molecules are not allowed. Its very familiarity leads to its toxicity •
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