title: DMPS-arsenic challenge test. II. Modulation of arsenic species, including monomethylarsonous acid (MMA(III)), excreted in human urine.
abstract: The administration of sodium 2,3-dimercapto-1-propane sulfonate (DMPS) to humans chronically exposed to inorganic arsenic in their drinking water resulted in the increased urinary excretion of arsenic, the appearance and identification of monomethylarsonous acid (MMA(III)) in their urine, and a large decrease in the concentration and percentage of urinary dimethylarsinic acid (DMA). This is the first time that MMA(III) has been detected in the urine. In vitro biochemical experiments were then designed and performed to understand the urinary appearance of MMA(III) and decrease of DMA. The DMPS-MMA(III) complex was not active as a substrate for the MMA(III) methyltransferase. The experimental results support the hypothesis that DMPS competes with endogenous ligands for MMA(III), forming a DMPS-MMA complex that is readily excreted in the urine and points out the need for studying the biochemical toxicology of MMA(III). It should be emphasized that MMA(III) was excreted in the urine only after DMPS administration. The results of these studies raise many questions about the potential central role of MMA(III) in the toxicity of inorganic arsenic and to the potential involvement of MMA(III) in the little-understood etiology of hyperkeratosis, hyperpigmentation, and cancer that can result from chronic inorganic arsenic exposure.
authors.affiliation: Department of Molecular and Cellular Biology, LSS Building, Room 444, Tucson, Arizona, 85721-0106, USA. aposhian@u.arizona.edu
authors.forename: H V
authors.initials: HV
authors.lastname: Aposhian
authors.forename: B
authors.initials: B
authors.lastname: Zheng
authors.forename: M M
authors.initials: MM
authors.lastname: Aposhian
authors.forename: X C
authors.initials: XC
authors.lastname: Le
authors.forename: M E
authors.initials: ME
authors.lastname: Cebrian
authors.forename: W
authors.initials: W
authors.lastname: Cullen
authors.forename: R A
authors.initials: RA
authors.lastname: Zakharyan
authors.forename: M
authors.initials: M
authors.lastname: Ma
authors.forename: R C
authors.initials: RC
authors.lastname: Dart
authors.forename: Z
authors.initials: Z
authors.lastname: Cheng
authors.forename: P
authors.initials: P
authors.lastname: Andrewes
authors.forename: L
authors.initials: L
authors.lastname: Yip
authors.forename: G F
authors.initials: GF
authors.lastname: O'Malley
authors.forename: R M
authors.initials: RM
authors.lastname: Maiorino
authors.forename: W
authors.initials: W
authors.lastname: Van Voorhies
authors.forename: S M
authors.initials: SM
authors.lastname: Healy
authors.forename: A
authors.initials: A
authors.lastname: Titcomb
mesh_terms: D000328:Adult; D000818:Animals; D020261:Arsenic Poisoning / Q000517:prevention & control; D001152:Arsenicals / Q000652:urine*; D002101:Cacodylic Acid / Q000652:urine*; D002614:Chelating Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008780:Methyltransferases / Q000037:antagonists & inhibitors; D008875:Middle Aged; D009942:Organometallic Compounds / Q000652:urine*; D011817:Rabbits; D014494:Unithiol / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D014873:Water Pollutants
chemical_list: D001152:Arsenicals; D002614:Chelating Agents; D009942:Organometallic Compounds; D014873:Water Pollutants; C406082:monomethylarsonous acid; D014494:Unithiol; D002101:Cacodylic Acid; D008780:Methyltransferases; C116336:methylarsonic acid methyltransferase