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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2010-6-14
pubmed:abstractText
Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes reactions which convert inorganic arsenic to methylated metabolites. This study determined whether the As3mt null genotype in the mouse modifies cytotoxic and proliferative effects seen in urinary bladders of wild type mice after exposure to inorganic arsenic. Female wild type C57BL/6 mice and As3mt KO mice were divided into 3 groups each (n=8) with free access to a diet containing 0, 100 or 150 ppm of arsenic as arsenite (As(III)). During the first week of As(III) exposure, As3mt KO mice exhibited severe and lethal systemic toxicity. At termination, urinary bladders of both As3mt KO and wild type mice showed hyperplasia by light microscopy. As expected, arsenic-containing granules were found in the superficial urothelial layer of wild type mice. In As3mt KO mice these granules were present in all layers of the bladder epithelium and were more abundant and larger than in wild type mice. Scanning electron microscopy of the bladder urothelium of As3mt KO mice treated with 100 ppm As(III) showed extensive superficial necrosis and hyperplastic changes. In As3mt KO mice, livers showed severe acute inflammatory changes and spleen size and lymphoid areas were decreased compared with wild type mice. Thus, diminished arsenic methylation in As3mt KO mice exacerbates systemic toxicity and the effects of As(III) on the bladder epithelium, showing that altered kinetic and dynamic behavior of arsenic can affect its toxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1096-0333
pubmed:author
pubmed:copyrightInfo
2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
246
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-7
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Severe systemic toxicity and urinary bladder cytotoxicity and regenerative hyperplasia induced by arsenite in arsenic (+3 oxidation state) methyltransferase knockout mice. A preliminary report.
pubmed:affiliation
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-3135, USA.
pubmed:publicationType
Journal Article