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Gut bacteria transform inorganic arsenate leading to more toxic arsenic species

(02.08.2010)


Background:
Arsenic pollution is a serious global health problem. It is driven by exposure to naturally-occurring sources – especially groundwater and food – and human activities associated with smelting and mining that create dust or liberate the metal from the soil.

High levels of arsenic occur naturally in India, Pakistan, parts of the United States and other hot spots around the world. Exposure to excess arsenic can lead to cancers of the lung, liver, bladder and kidney.

The toxicity of arsenic compounds differ by orders of magnitude depending on the oxidation state of arsenic and the grade of methylation with methylated trivalent species—monomethylarsonous acid (MMAIII), dimethylarsinous acid (DMAIII), and arsenous acid (iAsIII)—being two orders of magnitude more cytotoxic than As acid (iAsV).


The new study:
 
Fig.1: Human gastrointestinal tract
An international research group now found that bacteria living in human intestines can change arsenic's chemistry, in some cases producing a more toxic form that is linked to cancer. While similar results have been found already in animal studies, this is the first report of arsenic becoming more harmful as it passes through the human digestive tract.

In this study, bacteria from a human intestine were cultured in a specialized system that simulates the digestive system, including the stomach, small intestine and colon. Researchers added either inorganic arsenic or four types of soils with arsenic naturally present. After incubation, the resulting mixtures were analyzed by arsenic speciation analysis using by LC-ICP-MS to determine the arsenic species being present.

They found that the bacteria altered a significant portion of the initial inorganic arsenic through methylation. In addition to the formation of monomethylarsonic acid, they detected the highly toxic monomethylarsonous acid. In this way, the microbes changed the arsenic from a less toxic form to a more toxic variety. The toxic varieties were formed from both pure inorganic arsenic and from inorganic arsenic present in soils, suggesting that this process occurs even with arsenic that adheres to soil particles.

These unexpected results highlight concern about increasing arsenic's toxicity when it is transformed in the gut and suggest that regulators may need to take into account the way exposures occur when determining the health risks associated with arsenic.


The new study

Tom Van de Wiele, Christina M. Gallawa, Kevin M. Kubachka, John T. Creed, Nicholas Basta, Elizabeth A. Dayton, Shane Whitacre, Gijs Du Laing, Karen Bradham, Arsenic Metabolism by Human Gut Microbiota upon in Vitro Digestion of Contaminated Soils, Environ. Health Perspect., 118/7 (2010) 1004-1009. doi:10.1289/ehp.0901794


Related studies

K.M. Kubachka, M.C. Kohan, S.D. Conklin, K. Herbin-Davis, J.T. Creed, D.J. Thomas, In vitro biotransformation of dimethylarsinic acid and trimethylarsine oxide by anaerobic microflora of mouse cecum analyzed by HPLC-ICP-MS and HPLC-ESI-MS, J. Anal. At. Spectrom., 24 (2009) 1062–1068. doi: 10.1039/b817820h

K.M. Kubachka, M.C. Kohan, K. Herbin-Davis, J.T. Creed, D.J. Thomas, Exploring the in vitro formation of trimethylarsine sulfide from dimethylthioarsinic acid in anaerobic microflora of mouse cecum using HPLC–ICP-MS and HPLC–ESI-MS, Toxicol. Appl. Pharmacol., 239/2 (2009) 137–143. doi: 10.1016/j.taap.2008.12.008

J. Meyer, K. Michalke, T. Kouril, R. Hensel, Volatilisation of metals and metalloids: an inherent feature of methanoarchaea?, Syst. Appl. Microbiol., 31 (2008) 81–87. doi: 10.1128/AEM.02933-07

M.J. Herbel, J.S. Blum, S.E. Hoeft, S.M. Cohen, L.L. Arnold, J. Lisak, et al., Dissimilatory arsenate reductase activity and arsenate-respiring bacteria in bovine rumen fluid, hamster feces, and the termite hindgut, FEMS Microbiol. Ecol., 41 (2002) 59–67. doi: 10.1111/j.1574-6941.2002.tb00966.x

L.L. Hall, S.E. George, M.J. Kohan, M. Styblo, D.J. Thomas, In vitro methylation of inorganic arsenic in mouse intestinal cecum, Toxicol. Appl. Pharmacol.,  147 (1997) 101–109. doi: 10.1016/taap.1997.8269


Related EVISA Resources

 EVISA brief summary: ICP-MS: A versatile detection system for speciation analysis

 EVISA brief summary: LC-ICP-MS: The most often used hyphenated system for speciation analysis
 EVISA Link database: Toxicity of arsenic species
 EVISA Brief summary: Speciation and Toxicity


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last time modified: August 3, 2010



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