D J Thomas

Summary

Affiliation: U.S. Environmental Protection Agency
Country: USA

Publications

  1. ncbi request reprint Tissue distribution and urinary excretion of dimethylated arsenic and its metabolites in dimethylarsinic acid- or arsenate-treated rats
    Blakely M Adair
    Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U S Environmental Protection Agency, 109 Alexander Drive, Research Triangle Park, NC 27709, USA
    Toxicol Appl Pharmacol 222:235-42. 2007
  2. pmc Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals
    David J Thomas
    Pharmacokinetics Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Exp Biol Med (Maywood) 232:3-13. 2007
  3. doi request reprint Arsenolysis and thiol-dependent arsenate reduction
    David J Thomas
    Pharmacokinetics Branch, Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U S Environmental Protection Agency, MD B143 1, 109 Alexander Drive, Research Triangle Park, North Carolina 27711, USA
    Toxicol Sci 117:249-52. 2010
  4. ncbi request reprint The cellular metabolism and systemic toxicity of arsenic
    D J Thomas
    Pharmacokinetics Branch, U S Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA
    Toxicol Appl Pharmacol 176:127-44. 2001
  5. pmc Arsenic (+ 3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate Ciona intestinalis
    David J Thomas
    Pharmacokinetics Branch, Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U S Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA
    Toxicol Sci 113:70-6. 2010
  6. ncbi request reprint Elucidating the pathway for arsenic methylation
    David J Thomas
    Pharmacokinetics Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U S Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Toxicol Appl Pharmacol 198:319-26. 2004
  7. ncbi request reprint Molecular processes in cellular arsenic metabolism
    David J Thomas
    Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, 109 T W Alexander Drive, Research Triangle Park, NC 27709, USA
    Toxicol Appl Pharmacol 222:365-73. 2007
  8. ncbi request reprint Strain-dependent disposition of inorganic arsenic in the mouse
    M F Hughes
    Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Toxicology 137:95-108. 1999
  9. ncbi request reprint Accumulation and metabolism of arsenic in mice after repeated oral administration of arsenate
    Michael F Hughes
    U S Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711, USA
    Toxicol Appl Pharmacol 191:202-10. 2003
  10. ncbi request reprint Total arsenic concentrations in toenails quantified by two techniques provide a useful biomarker of chronic arsenic exposure in drinking water
    Blakely M Adair
    Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, United States Environmental Protection Agency, North Carolina 27711, USA
    Environ Res 101:213-20. 2006

Collaborators

Detail Information

Publications33

  1. ncbi request reprint Tissue distribution and urinary excretion of dimethylated arsenic and its metabolites in dimethylarsinic acid- or arsenate-treated rats
    Blakely M Adair
    Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U S Environmental Protection Agency, 109 Alexander Drive, Research Triangle Park, NC 27709, USA
    Toxicol Appl Pharmacol 222:235-42. 2007
    ..One or more of these metabolites could be the species causing alterations of cellular function that lead to tumors in the urinary bladder...
  2. pmc Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals
    David J Thomas
    Pharmacokinetics Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Exp Biol Med (Maywood) 232:3-13. 2007
    ..Additional information on the structure and function of the enzyme will be needed to develop a more comprehensive model for this pathway...
  3. doi request reprint Arsenolysis and thiol-dependent arsenate reduction
    David J Thomas
    Pharmacokinetics Branch, Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U S Environmental Protection Agency, MD B143 1, 109 Alexander Drive, Research Triangle Park, North Carolina 27711, USA
    Toxicol Sci 117:249-52. 2010
    ..Integrating these reductive processes into a conceptual model for arsenic metabolism may provide new insights into the cellular machinery for handling this toxic metalloid...
  4. ncbi request reprint The cellular metabolism and systemic toxicity of arsenic
    D J Thomas
    Pharmacokinetics Branch, U S Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA
    Toxicol Appl Pharmacol 176:127-44. 2001
    ..Given the considerable interest in the dose-response relationships for arsenic as a toxin and a carcinogen, understanding the metabolism of arsenic may be critical to assessing the risk associated with chronic exposure to this element...
  5. pmc Arsenic (+ 3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate Ciona intestinalis
    David J Thomas
    Pharmacokinetics Branch, Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U S Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA
    Toxicol Sci 113:70-6. 2010
    ....
  6. ncbi request reprint Elucidating the pathway for arsenic methylation
    David J Thomas
    Pharmacokinetics Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U S Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Toxicol Appl Pharmacol 198:319-26. 2004
    ..A scheme linking cyt19 and thioredoxin-thioredoxin reductase in the methylation and reduction of arsenicals is proposed...
  7. ncbi request reprint Molecular processes in cellular arsenic metabolism
    David J Thomas
    Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, 109 T W Alexander Drive, Research Triangle Park, NC 27709, USA
    Toxicol Appl Pharmacol 222:365-73. 2007
    ..It may also be useful in development of biologically based dose-response models describing the toxic and carcinogenic actions of arsenicals...
  8. ncbi request reprint Strain-dependent disposition of inorganic arsenic in the mouse
    M F Hughes
    Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Toxicology 137:95-108. 1999
    ..A better understanding of the role of phenotype in the disposition and toxicity of iAs would reduce the uncertainty in arsenic risk assessment...
  9. ncbi request reprint Accumulation and metabolism of arsenic in mice after repeated oral administration of arsenate
    Michael F Hughes
    U S Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711, USA
    Toxicol Appl Pharmacol 191:202-10. 2003
    ..A trimethylated metabolite was also detected in the liver. Tissue accumulation of arsenic after repeated po exposure to arsenate in the mouse corresponds to the known human target organs for iAs-induced carcinogenicity...
  10. ncbi request reprint Total arsenic concentrations in toenails quantified by two techniques provide a useful biomarker of chronic arsenic exposure in drinking water
    Blakely M Adair
    Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, United States Environmental Protection Agency, North Carolina 27711, USA
    Environ Res 101:213-20. 2006
    ..These results suggest that toenails are a better biomarker of chronic As exposure than urine in the current study, because the sequestration of As in toenails provides an integration of exposure over time that does not occur in urine...
  11. pmc Tissue dosimetry, metabolism and excretion of pentavalent and trivalent dimethylated arsenic in mice after oral administration
    Michael F Hughes
    US Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711, USA
    Toxicol Appl Pharmacol 227:26-35. 2008
    ..TMAO was detected in tissues of the high dose DMA(V) group. The low acute toxicity of DMA(V) in the mouse appears to be due in part to its minimal retention and rapid elimination...
  12. pmc Tissue dosimetry, metabolism and excretion of pentavalent and trivalent monomethylated arsenic in mice after oral administration
    Michael F Hughes
    U S Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711, USA
    Toxicol Appl Pharmacol 208:186-97. 2005
    ..Based on urinary analysis, administered dose of MMA(V) did not affect the level of its metabolites excreted. In the tested range, dose affects the absorption, distribution and route of excretion of MMA(V) but not its metabolism...
  13. ncbi request reprint Health effects and risk assessment of arsenic
    Charles O Abernathy
    Office of Science and Technology, U S Environmental Protection Agency, Washington, DC 20422, USA
    J Nutr 133:1536S-8S. 2003
    ..After reviewing the As database, the U.S. Environmental Protection Agency promulgated a maximum contaminant level for As in drinking water of 10 micro g/L...
  14. doi request reprint Arsenic (+3 oxidation state) methyltransferase genotype affects steady-state distribution and clearance of arsenic in arsenate-treated mice
    Michael F Hughes
    Pharmacokinetics Branch, Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Toxicol Appl Pharmacol 249:217-23. 2010
    ..Altered retention and tissue tropism of arsenic in As3mt knockout mice could affect the toxic or carcinogenic effects associated with exposure to this metalloid or its methylated metabolites...
  15. pmc Impact of life stage and duration of exposure on arsenic-induced proliferative lesions and neoplasia in C3H mice
    Gene J Ahlborn
    United States Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC, USA
    Toxicology 262:106-13. 2009
    ..The paradoxical nature of these effects may be related to altered lipid metabolism, the effective dose in each target organ, and/or the shorter one-year observational period...
  16. pmc Excretion of arsenic in urine as a function of exposure to arsenic in drinking water
    R L Calderon
    Human Studies Division, National Health and Environmental Effects Research Laboratory, Research Triangle Park, North Carolina 27711, USA
    Environ Health Perspect 107:663-7. 1999
    ....
  17. ncbi request reprint Methylated trivalent arsenic species are genotoxic
    M J Mass
    Environmental Carcinogenesis Division MD 68, National Health and Environmental Effects Research Laboratory Office of Research and Development, U S Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Chem Res Toxicol 14:355-61. 2001
    ....
  18. ncbi request reprint Consequences of acute and chronic exposure to arsenic in children
    Rebecca L Calderon
    Epidemiology and Biomarker Branch, MD 58A, NHEERL, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Pediatr Ann 33:461-6. 2004
    ..Such procedures will limit arsenic exposure to a minimum...
  19. ncbi request reprint Arsenic (+3 oxidation state) methyltransferase and the inorganic arsenic methylation phenotype
    Jiaxin Li
    Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Toxicol Appl Pharmacol 204:164-9. 2005
    ..This lineage-specific loss of function caused by the deletion event must have occurred in the Pan lineage after Homo-Pan divergence about 5 million years ago...
  20. ncbi request reprint A novel S-adenosyl-L-methionine:arsenic(III) methyltransferase from rat liver cytosol
    Shan Lin
    Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 277:10795-803. 2002
    ..Because methylation of arsenic is a critical feature of its metabolism, characterization of this enzyme will improve our understanding of this metalloid's metabolism and its actions as a toxin and a carcinogen...
  21. pmc The role of biomethylation in toxicity and carcinogenicity of arsenic: a research update
    Miroslav Styblo
    Department of Pediatrics, Center for Environmental Medicine and Lung Biology, Burnett Womack Clinical Sciences Building, University of North Carolina, Chapel Hill, NC 27599 7220, USA
    Environ Health Perspect 110:767-71. 2002
    ....
  22. ncbi request reprint Selenium compounds modulate the activity of recombinant rat AsIII-methyltransferase and the methylation of arsenite by rat and human hepatocytes
    Felecia S Walton
    Department of Pediatrics, Curriculum in Toxicology, Division of Drug Delivery and Disposition, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Chem Res Toxicol 16:261-5. 2003
    ....
  23. ncbi request reprint Endogenous reductants support the catalytic function of recombinant rat cyt19, an arsenic methyltransferase
    Stephen B Waters
    Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
    Chem Res Toxicol 17:404-9. 2004
    ..Thus, cyt19 appears to possess both AsIII methyltransferase and AsV reductase activities...
  24. pmc Metabolism and toxicity of arsenic in human urothelial cells expressing rat arsenic (+3 oxidation state)-methyltransferase
    Zuzana Drobna
    Department of Pediatrics, University of North Carolina, Chapel Hill, NC 27599 2774, USA
    Toxicol Appl Pharmacol 207:147-59. 2005
    ..Thus, the production and accumulation of MAs(III) is a key factor contributing to the toxicity of acute iAs exposures in methylating cells...
  25. pmc shRNA silencing of AS3MT expression minimizes arsenic methylation capacity of HepG2 cells
    Zuzana Drobna
    Department of Nutrition, Curriculum in Toxicology, and Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina at Chapel Hill, 27599 2774, USA
    Chem Res Toxicol 19:894-8. 2006
    ..In comparison, the capacity to methylate iAs decreased only by 70%. These data suggest that AS3MT is the major enzyme in this pathway, although an AS3MT-independent process may contribute to iAs methylation in human hepatic cells...
  26. ncbi request reprint Glutathione modulates recombinant rat arsenic (+3 oxidation state) methyltransferase-catalyzed formation of trimethylarsine oxide and trimethylarsine
    Stephen B Waters
    Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Chem Res Toxicol 17:1621-9. 2004
    ..The regulation of this pathway by intracellular glutathione may be an important determinant of the pattern and extent of formation of arsenicals...
  27. ncbi request reprint Interindividual variation in the metabolism of arsenic in cultured primary human hepatocytes
    Zuzana Drobna
    Department of Pediatrics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Toxicol Appl Pharmacol 201:166-77. 2004
    ..Thus, genetic polymorphism of cyt19 along with other cellular factors is likely responsible for interindividual differences in the capacity of primary human hepatocytes to retain and metabolize iAs(III)...
  28. ncbi request reprint In vitro biotransformation of an arsenosugar by mouse anaerobic cecal microflora and cecal tissue as examined using IC-ICP-MS and LC-ESI-MS/MS
    Sean D Conklin
    US EPA, ORD, NERL, Microbiological and Chemical Exposure Assessment Research Division, Cincinnati, OH 45268, USA
    Analyst 131:648-55. 2006
    ..This biotransformation may affect the subsequent absorption, metabolism, and disposition of arsenic present in arsenosugars...
  29. ncbi request reprint Tissue levels of arsenicals and skin tumor response following administration of monomethylarsonous acid and arsenite to K6/ODC mice
    Yan Chen
    ODC Mouse Group Inc, 1209 Childs Ave, Drexel Hill, PA 19026, USA
    J Environ Pathol Toxicol Oncol 27:43-52. 2008
    ....
  30. ncbi request reprint Differential activation of AP-1 in human bladder epithelial cells by inorganic and methylated arsenicals
    Zuzana Drobna
    Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina 27599 7220, USA
    FASEB J 17:67-9. 2003
    ..These results indicate that an ERK-dependent signal transduction pathway is at least partially responsible for c-Jun phosphorylation and AP-1 activation in UROtsa cells exposed to inorganic or methylated trivalent arsenicals...
  31. pmc Arsenicals in maternal and fetal mouse tissues after gestational exposure to arsenite
    Vicenta Devesa
    Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Toxicology 224:147-55. 2006
    ..Tissue concentration-dependent processes could affect kinetics of transfer of inorganic arsenic or its metabolites from mother to fetus...
  32. pmc Molecular mechanisms of the diabetogenic effects of arsenic: inhibition of insulin signaling by arsenite and methylarsonous acid
    David S Paul
    Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7461, USA
    Environ Health Perspect 115:734-42. 2007
    ....
  33. ncbi request reprint High-throughput identification of catalytic redox-active cysteine residues
    Dmitri E Fomenko
    Department of Biochemistry, University of Nebraska, Lincoln, NE 68588, USA
    Science 315:387-9. 2007
    ..Rapid accumulation of sequence information from genomic and metagenomic projects should allow detection of many additional oxidoreductase families as well as identification of redox-active Cys in these proteins...