Research Interests - Toxicology
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Arsenic-Selenium Antagonism in Mammals
J. Gailer, G. N.
George, I. J. Pickering, R. C. Prince, S. C. Ringwald, J. E. Pemberton, R. S.
Glass, H. S. Younis, D. W. DeYoung and H. V. Aposhian,
"A Metabolic Link
Between Arsenite and Selenite: The Seleno-bis(S-glutathionyl) Arsinium
Ion",
Journal of the American Chemical Society, 122, 4637-4639 (2000)
It has been known for several decades that a surprising relationship exists between the toxic affects of arsenic and selenium upon mammals. Arsenite has been notorious as a poison since the Middle Ages. Selenium is an essential trace element but at elevated amounts it is also toxic, and selenite is about as toxic as arsenite. However, if equal (and in isolation lethal) quantities of arsenite and selenite are administered at the same time, their toxic properties are somehow cancelled out. Our group used X-ray absorption spectroscopy in combination with other techniques to investigate this antagonism. It was found that arsenic and selenium are excreted in the bile in a 1:1 molar ratio and they form the chemically unusual seleno-bis(S-glutathionyl) arsinium ion which contains arsenic bound to two sulfurs from glutathione, and to a single selenium which has no other ligands. The fact that the selenium and arsenic chemistries are interlinked may have important implications for chronic arsenic poisoning such as is found in Bangladesh. Since the body's detoxification mechanisms excrete one selenium for each arsenic atom removed, this could lead to selenium-deficiency, especially if the diet is not selenium-rich. The symptoms of chronic arsenic toxicity and selenium deficiency show significant similarities. Hence, selenium supplements might be greatly beneficial in populations exposed to chronic levels of arsenic.
The Chemical Form of Mercury in Fish
H. H.
Harris,
“Brevia:
The chemical form of mercury in fish.”
Science, 301(5637), 1203 (2003)
The presence of "methyl mercury" in fish is well-known, but until this study the detailed chemical identity of the mercury had remained a mystery. Our group used X-ray absorption spectroscopy to show that the chemical form of mercury involves a single aliphatic sulfur atom (most likely from glutathione) in addition to the methyl group. The study presents significant new knowledge - because the toxic properties of mercury (or any element) are critically dependent upon its chemical form - and represents an important milestone in developing an understanding of how harmful mercury in fish might actually be. The study was carried out at the Stanford Synchrotron Radiation Laboratory using structural molecular biology beam line 9-3. The very high flux, excellent beam stability and state-of-the-art detector technology allowed us to measure samples of fish containing micromolar levels of mercury, much lower than had previously been possible. This opens up the possibility for future studies of mercury in situ and in vivo at physiologically relevant concentrations.
Funding for this research was provided by the U.S. Department of Energy, Office of Biological and Environmental Research and by the U.S. National Institutes of Health, National Center for Research Resources, Biomedical Technology Program.
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Last Modified April 23, 2004