Research Topics
| D J ThomasSummaryAffiliation: U.S. Environmental Protection Agency Country: USA Publications
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Detail Information
Publications
Tissue distribution and urinary excretion of dimethylated arsenic and its metabolites in dimethylarsinic acid- or arsenate-treated ratsBlakely 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...
Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicalsDavid 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...
Arsenolysis and thiol-dependent arsenate reductionDavid 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...
The cellular metabolism and systemic toxicity of arsenicD 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...
Arsenic (+ 3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate Ciona intestinalisDavid 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....
Elucidating the pathway for arsenic methylationDavid 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...
Molecular processes in cellular arsenic metabolismDavid 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...
Strain-dependent disposition of inorganic arsenic in the mouseM 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...
Accumulation and metabolism of arsenic in mice after repeated oral administration of arsenateMichael 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...
Total arsenic concentrations in toenails quantified by two techniques provide a useful biomarker of chronic arsenic exposure in drinking waterBlakely 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...
Tissue dosimetry, metabolism and excretion of pentavalent and trivalent dimethylated arsenic in mice after oral administrationMichael 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...
Tissue dosimetry, metabolism and excretion of pentavalent and trivalent monomethylated arsenic in mice after oral administrationMichael 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...
Health effects and risk assessment of arsenicCharles 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...
Arsenic (+3 oxidation state) methyltransferase genotype affects steady-state distribution and clearance of arsenic in arsenate-treated miceMichael 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...
Impact of life stage and duration of exposure on arsenic-induced proliferative lesions and neoplasia in C3H miceGene 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...
Excretion of arsenic in urine as a function of exposure to arsenic in drinking waterR 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....
Methylated trivalent arsenic species are genotoxicM 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....
Consequences of acute and chronic exposure to arsenic in childrenRebecca 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...
Arsenic (+3 oxidation state) methyltransferase and the inorganic arsenic methylation phenotypeJiaxin 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...
A novel S-adenosyl-L-methionine:arsenic(III) methyltransferase from rat liver cytosolShan 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...
The role of biomethylation in toxicity and carcinogenicity of arsenic: a research updateMiroslav 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....
Selenium compounds modulate the activity of recombinant rat AsIII-methyltransferase and the methylation of arsenite by rat and human hepatocytesFelecia 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....
Endogenous reductants support the catalytic function of recombinant rat cyt19, an arsenic methyltransferaseStephen 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...
Metabolism and toxicity of arsenic in human urothelial cells expressing rat arsenic (+3 oxidation state)-methyltransferaseZuzana 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...
shRNA silencing of AS3MT expression minimizes arsenic methylation capacity of HepG2 cellsZuzana 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...
Glutathione modulates recombinant rat arsenic (+3 oxidation state) methyltransferase-catalyzed formation of trimethylarsine oxide and trimethylarsineStephen 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...
Interindividual variation in the metabolism of arsenic in cultured primary human hepatocytesZuzana 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)...
In vitro biotransformation of an arsenosugar by mouse anaerobic cecal microflora and cecal tissue as examined using IC-ICP-MS and LC-ESI-MS/MSSean 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...
Tissue levels of arsenicals and skin tumor response following administration of monomethylarsonous acid and arsenite to K6/ODC miceYan Chen
ODC Mouse Group Inc, 1209 Childs Ave, Drexel Hill, PA 19026, USA
J Environ Pathol Toxicol Oncol 27:43-52. 2008....
Differential activation of AP-1 in human bladder epithelial cells by inorganic and methylated arsenicalsZuzana 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...
Arsenicals in maternal and fetal mouse tissues after gestational exposure to arseniteVicenta 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...
Molecular mechanisms of the diabetogenic effects of arsenic: inhibition of insulin signaling by arsenite and methylarsonous acidDavid 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....
High-throughput identification of catalytic redox-active cysteine residuesDmitri 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...
