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Title: Arsenic (+ 3 oxidation state) methyltransferase genotype affects steady-state distribution and clearance of arsenic in arsenate-treated mice

Abstract

Arsenic (+ 3 oxidation state) methyltransferase (As3mt) catalyzes formation of mono-, di-, and tri-methylated metabolites of inorganic arsenic. Distribution and retention of arsenic were compared in adult female As3mt knockout mice and wild-type C57BL/6 mice using a regimen in which mice received daily oral doses of 0.5 mg of arsenic as arsenate per kilogram of body weight. Regardless of genotype, arsenic body burdens attained steady state after 10 daily doses. At steady state, arsenic body burdens in As3mt knockout mice were 16 to 20 times greater than in wild-type mice. During the post dosing clearance period, arsenic body burdens declined in As3mt knockout mice to {approx} 35% and in wild-type mice to {approx} 10% of steady-state levels. Urinary concentration of arsenic was significantly lower in As3mt knockout mice than in wild-type mice. At steady state, As3mt knockout mice had significantly higher fractions of the body burden of arsenic in liver, kidney, and urinary bladder than did wild-type mice. These organs and lung had significantly higher arsenic concentrations than did corresponding organs from wild-type mice. Inorganic arsenic was the predominant species in tissues of As3mt knockout mice; tissues from wild-type mice contained mixtures of inorganic arsenic and its methylated metabolites. Diminishedmore » capacity for arsenic methylation in As3mt knockout mice prolongs retention of inorganic arsenic in tissues and affects whole body clearance of arsenic. 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.« less

Authors:
; ;  [1]; ;  [2]
  1. 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 (United States)
  2. Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 (United States)
Publication Date:
OSTI Identifier:
21529105
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 249; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2010.09.017; PII: S0041-008X(10)00359-5; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; ADULTS; ARSENATES; ARSENIC; BODY BURDEN; CLEARANCE; DISTRIBUTION; DOSES; FEMALES; GENOTYPE; KIDNEYS; LIVER; LUNGS; METABOLITES; METHYLATION; MICE; RETENTION; TOXICITY; VALENCE; AGE GROUPS; ANIMALS; ARSENIC COMPOUNDS; BODY; CHEMICAL REACTIONS; DIGESTIVE SYSTEM; ELEMENTS; GLANDS; MAMMALS; ORGANS; OXYGEN COMPOUNDS; RESPIRATORY SYSTEM; RODENTS; SEMIMETALS; VERTEBRATES

Citation Formats

Hughes, Michael F, Edwards, Brenda C, Herbin-Davis, Karen M, Saunders, Jesse, Styblo, Miroslav, and Thomas, David J., E-mail: thomas.david@epa.gov. Arsenic (+ 3 oxidation state) methyltransferase genotype affects steady-state distribution and clearance of arsenic in arsenate-treated mice. United States: N. p., 2010. Web. doi:10.1016/j.taap.2010.09.017.
Hughes, Michael F, Edwards, Brenda C, Herbin-Davis, Karen M, Saunders, Jesse, Styblo, Miroslav, & Thomas, David J., E-mail: thomas.david@epa.gov. Arsenic (+ 3 oxidation state) methyltransferase genotype affects steady-state distribution and clearance of arsenic in arsenate-treated mice. United States. https://doi.org/10.1016/j.taap.2010.09.017
Hughes, Michael F, Edwards, Brenda C, Herbin-Davis, Karen M, Saunders, Jesse, Styblo, Miroslav, and Thomas, David J., E-mail: thomas.david@epa.gov. 2010. "Arsenic (+ 3 oxidation state) methyltransferase genotype affects steady-state distribution and clearance of arsenic in arsenate-treated mice". United States. https://doi.org/10.1016/j.taap.2010.09.017.
@article{osti_21529105,
title = {Arsenic (+ 3 oxidation state) methyltransferase genotype affects steady-state distribution and clearance of arsenic in arsenate-treated mice},
author = {Hughes, Michael F and Edwards, Brenda C and Herbin-Davis, Karen M and Saunders, Jesse and Styblo, Miroslav and Thomas, David J., E-mail: thomas.david@epa.gov},
abstractNote = {Arsenic (+ 3 oxidation state) methyltransferase (As3mt) catalyzes formation of mono-, di-, and tri-methylated metabolites of inorganic arsenic. Distribution and retention of arsenic were compared in adult female As3mt knockout mice and wild-type C57BL/6 mice using a regimen in which mice received daily oral doses of 0.5 mg of arsenic as arsenate per kilogram of body weight. Regardless of genotype, arsenic body burdens attained steady state after 10 daily doses. At steady state, arsenic body burdens in As3mt knockout mice were 16 to 20 times greater than in wild-type mice. During the post dosing clearance period, arsenic body burdens declined in As3mt knockout mice to {approx} 35% and in wild-type mice to {approx} 10% of steady-state levels. Urinary concentration of arsenic was significantly lower in As3mt knockout mice than in wild-type mice. At steady state, As3mt knockout mice had significantly higher fractions of the body burden of arsenic in liver, kidney, and urinary bladder than did wild-type mice. These organs and lung had significantly higher arsenic concentrations than did corresponding organs from wild-type mice. Inorganic arsenic was the predominant species in tissues of As3mt knockout mice; tissues from wild-type mice contained mixtures of inorganic arsenic and its methylated metabolites. Diminished capacity for arsenic methylation in As3mt knockout mice prolongs retention of inorganic arsenic in tissues and affects whole body clearance of arsenic. 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.},
doi = {10.1016/j.taap.2010.09.017},
url = {https://www.osti.gov/biblio/21529105}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 249,
place = {United States},
year = {Wed Dec 15 00:00:00 EST 2010},
month = {Wed Dec 15 00:00:00 EST 2010}
}