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Environmental problems - Chemical approaches

Commonalities in Metabolism of Arsenicals

Blakely M. Adair A , Stephen B. Waters B , Vicenta Devesa C , Zuzana Drobna D , Miroslav Styblo C D and David J. Thomas A E

A Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.

B Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC 27599, USA.

C Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina, Chapel Hill, NC 27599, USA.

D Department of Nutrition, School of Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.

E Corresponding author. Email: thomas.david@epamail.epa.gov

Blakely M. Adair received a Ph.D. in environmental toxicology from Texas Tech University in 2002. Since then she has been a postdoctoral fellow at the U.S. Environmental Protection Agency working with David Thomas. Her research focuses on the environmental analytical chemistry of toxicologically relevant contaminants, including method development for quantification of arsenicals in biological samples.

Stephen B. Waters received a Ph.D. in molecular biology from Wake Forest University School of Medicine in 2001. He was a postdoctoral fellow in the Curriculum in Toxicology at the University of North Carolina-Chapel Hill from 2001 until 2004 and worked with David Thomas. He is currently studying TAT-mediated protein transduction in the Department of Cardiology at the University of Illinois-Chicago.

Vicenta Devesa received a Ph.D. in analytical chemistry in 2002 from the University of Valencia. From 2003 to 2005 she held a MECD/Fulbright Postdoctoral Fellowship at the University of North Carolina at Chapel Hill and worked with Miroslav Styblo. Her research interests include speciation of arsenicals in biological samples. She is currently affiliated with the Institute of Agrochemistry and Food Technology, Burjassot, Valencia, Spain.

Zuzana Drobna received a Ph.D. in biochemistry from Slovak Academy of Sciences in Bratislava in 1997. During graduate studies she worked at the Max Delbruck Institute in Berlin. She has been a postdoctoral fellow with Miroslav Styblo since 2001. Her research investigates the role of arsenic methylation in modulation of its toxic and cancer promoting effects in mammalian cells.

Miroslav Styblo is Research Associate Professor in the Department of Nutrition, University of North Carolina at Chapel Hill. His background and interests are in biochemical toxicology and nutritional biochemistry. Current research focuses on the metabolism and molecular toxicity of arsenic, on identification of biomarkers for exposure and chronic toxicity of arsenic, and on interactions between arsenic and essential metals and metalloids.

David J. Thomas is Research Toxicologist in the Experimental Toxicology Division of the National Health and Environmental Effects Research Laboratory of the U.S. Environmental Protection Agency. He is interested in the metabolism of metals and metalloids and in development of novel methods to identify metals and metalloids in biological matrices.

Environmental Chemistry 2(3) 161-166 http://dx.doi.org/10.1071/EN05054
Submitted: 7 July 2005  Accepted: 19 August 2005   Published: 27 September 2005

Environmental Context. Health effects associated with inorganic arsenic include various cancers and increased risk of diabetes. Millions of people in Bangladesh and India are at risk through use of contaminated drinking water. When humans ingest inorganic arsenic, it is rapidly converted to methylated metabolites. Although this methylation process is largely understood, the metabolism of other arsenicals (e.g. arsenosugars to dimethylarsenic) is very unclear. Connections among pathways for metabolism of various arsenicals are now being elucidated. Commonalities and differences in these pathways may be important determinants of the risk associated with exposure to these agents.

Abstract. Elucidating the pathway of inorganic arsenic metabolism shows that some of methylated arsenicals formed as intermediates and products are reactive and toxic species. Hence, methylated arsenicals likely mediate at least some of the toxic and carcinogenic effects associated with exposure to arsenic. Trimethylarsonium compounds and arsenosugars are two other classes of arsenicals to which humans are routinely exposed and there is evidence that both classes are metabolized to produce methylated arsenicals. Here, we review evidence for production of methylated metabolism and consider the challenges posed in unraveling a complex web for metabolism of arsenicals in humans.

Keywords. arsenic — bioavailability — contaminant uptake — metabolism-affecting agents


[1]  Yoshida T.Yamauchi H.Sun G. F.2004Toxicol. Appl. Pharmacol.198243doi:10.1016/J.TAAP.2003.10.022

[2]  Smith A. H.Lingas E. O.Rahman M.2000Bull. World Health Organ.781093

[3]  A. A. Maherg, Venomous Earth 2005 (Macmillan: New York, NY).

[4]  Nemeti B.Gregus Z.2005Toxicol. Sci.85847

[5]  Gregus Z.Nemeti B.2005Toxicol. Sci.85859doi:10.1093/TOXSCI/KFI158

[6]  Waters S. B.Devesa V.Del Razo L. M.Styblo M.Thomas D. J.2004Chem. Res. Toxicol.17404doi:10.1021/TX0342161

[7]  Waters S. B.Devesa V.Fricke M. W.Creed J. T.Styblo M.Thomas D. J.2004Chem. Res. Toxicol.171621doi:10.1021/TX0497853

[8]  Drobna Z.Waters S. B.Devesa V.Harmon A. W.Thomas D. J.2005Toxicol. Appl. Pharmacol.207147doi:10.1016/J.TAAP.2004.12.007

[9]  Wei M.Wanibuchi H.Yamamoto S.Li W.Fukushima S.1999Carcinogenesis201873doi:10.1093/CARCIN/20.9.1873

[10]  Shen J.Wanibuchi H.Salim E. I.Wei M.Kinoshita A.Yoshida K.Endo G.Fukushima S.2003Carcinogenesis241827doi:10.1093/CARCIN/BGG143

[11]  Thomas D. J.Styblo M.Lin S.2001Toxicol. Appl. Pharmacol.176127doi:10.1006/TAAP.2001.9258

[12]  Ritchie A. W.Edmonds J. S.Goessler W.Jenkins R. O.2004FEMS Microbiol. Lett.23595doi:10.1016/J.FEMSLE.2004.04.016

[13]  Fujihara J.Kunito T.Kubota R.Tanabe S.2003Comp. Biochem. Physiol C: Toxicol. Pharmacol.136287doi:10.1016/J.CCA.2003.10.001

[14]  Clowes L. A.Francesconi K. A.2004Comp. Biochem. Physiol. C: Toxicol. Pharmacol.13735doi:10.1016/J.CCA.2003.11.003

[15]  Jenkins R. O.Ritchie A. W.Edmonds J. S.Goessler W.Molenat N.Kuehnelt D.Harrington C. F.Sutton P. G.2003Arch. Microbiol.180142doi:10.1007/S00203-003-0569-9

[16]  Mann P. J. G.Woodward H. E.Quastel J. H.1938Biochem. J.321024

[17]  Vahter M.Marafante E.Dencker L.1983Sci. Total Environ.30197

[18]  Marafante E.Vahter M.Dencker L.1984Sci. Total Environ.34223doi:10.1016/0048-9697(84)90065-2

[19]  Heinrich-Ramm R.Mindt-Prufert S.Szadkowski D.2002J. Chromatogr.778263doi:10.1016/S0378-4347(01)00443-1

[20]  Christakopoulos A.Norin H.Sandstrom M.Thor H.Moldeus P.Ryhage R.1988J. Appl. Toxicol.8119

[21]  Chern M. K.Pietruszko R.1999Biochem. Cell Biol.77179

[22]  Andrewes P.Kitchin K. T.Wallace K.2003Chem. Res. Toxicol.16994doi:10.1021/TX034063H

[23]  Jukes T. H.Welch A. D.1942J. Biol. Chem.14619

[24]  Nørum U.Lai V. W.Pergantis S. A.Cullen W. R.2005J. Environ. Monit.7122

[25]  Yamauchi H.Takahashi K.Mashiko M.Saithoh J.Yamamura Y.1992Appl. Organometal. Chem.6383doi:10.1002/AOC.590060412

[26]  Le X. C.Cullen W. R.Reimer K. J.1994Clin. Chem.40617

[27]  Ma M.Le X. C.1998Clin. Chem.44539

[28]  Francesconi K. A.Tanggaar R.McKenzie C. J.Goessler W.2002Clin. Chem.4892

[29]  Feldmann J.John K.Pengprecha P.2000Fresenius J. Anal. Chem.368116

[30]  Hansen H. R.Raab A.Francesconi K. A.Feldmann J.2003Environ. Sci. Technol.37845doi:10.1021/ES026074N

[31]  Hansen H. R.Pickford R.Thomas-Oates J.Jaspers M.Feldmann J.2004Angew. Chem. Int. Ed.43337doi:10.1002/ANIE.200352740

[32]  Del Razo L. M.Styblo M.Cullen W. R.Thomas D. J.2001Toxicol. Appl. Pharmacol.174282doi:10.1006/TAAP.2001.9226

[33]  Devesa V.Del Razo L. M.Adair B.Drobna Z.Waters S. B.Hughes M. F.Styblo M.Thomas D. J.2004J. Anal. At. Spectrom.191460doi:10.1039/B407388F

[34]  Schmeisser E.Raml R.Francesconi K. A.Kuehnelt D.Lindberg A. L.Soros C.Goessler W.2004Chem. Commun.211824doi:10.1039/B406917J

[35]  Hansen H. R.Raab A.Jaspars M.Milne B. F.Feldmann J.2004Chem. Res. Toxicol.171086doi:10.1021/TX049978Q

[36]  Jay J. A.Blute N. K.Hemond H. F.Durant J. L.2004Water Res.381155doi:10.1016/J.WATRES.2003.11.014

[37]  Hansen H. R.Jaspars M.Feldmann J.2004Analyst1291058doi:10.1039/B409661B

[38]  Suzuki K. T.Mandal B. K.Katagiri A.Sakuma Y.Kawakami A.Ogra Y.Yamaguchi K.Sei Y.Yamanaka K.Anzai K.Ohmichi M.Takayama H.Aimi N.2004Chem. Res. Toxicol.17914doi:10.1021/TX049963S

[39]  Eto K.Kimura H.2002J. Biol. Chem.27742680doi:10.1074/JBC.M205835200

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