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Title: Severe systemic toxicity and urinary bladder cytotoxicity and regenerative hyperplasia induced by arsenite in arsenic (+ 3 oxidation state) methyltransferase knockout mice. A preliminary report

Abstract

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{sup III}). During the first week of As{sup 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{sup 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 withmore » wild type mice. Thus, diminished arsenic methylation in As3mt KO mice exacerbates systemic toxicity and the effects of As{sup III} on the bladder epithelium, showing that altered kinetic and dynamic behavior of arsenic can affect its toxicity.« less

Authors:
; ;  [1];  [1];  [1]; ;  [2]
  1. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-3135 (United States)
  2. 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, NC 27711 (United States)
Publication Date:
OSTI Identifier:
21460182
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 246; Journal Issue: 1-2; Other Information: DOI: 10.1016/j.taap.2010.04.013; PII: S0041-008X(10)00140-7; 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:
60 APPLIED LIFE SCIENCES; ARSENIC; ARSENIC COMPOUNDS; BLADDER; CELL PROLIFERATION; EPITHELIUM; INFLAMMATION; LIVER; METABOLITES; METHYL TRANSFERASES; MICE; SCANNING ELECTRON MICROSCOPY; TOXICITY; ANIMAL TISSUES; ANIMALS; BODY; CARBON-GROUP TRANSFERASES; DIGESTIVE SYSTEM; ELECTRON MICROSCOPY; ELEMENTS; ENZYMES; GLANDS; MAMMALS; MICROSCOPY; ORGANIC COMPOUNDS; ORGANS; PATHOLOGICAL CHANGES; PROTEINS; RODENTS; SEMIMETALS; SYMPTOMS; TRANSFERASES; URINARY TRACT; VERTEBRATES

Citation Formats

Yokohira, Masanao, Arnold, Lora L, Pennington, Karen L, Suzuki, Shugo, Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Kakiuchi-Kiyota, Satoko, Herbin-Davis, Karen, Thomas, David J, and Cohen, Samuel M., E-mail: scohen@unmc.ed. Severe systemic toxicity and urinary bladder cytotoxicity and regenerative hyperplasia induced by arsenite in arsenic (+ 3 oxidation state) methyltransferase knockout mice. A preliminary report. United States: N. p., 2010. Web. doi:10.1016/j.taap.2010.04.013.
Yokohira, Masanao, Arnold, Lora L, Pennington, Karen L, Suzuki, Shugo, Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Kakiuchi-Kiyota, Satoko, Herbin-Davis, Karen, Thomas, David J, & Cohen, Samuel M., E-mail: scohen@unmc.ed. Severe systemic toxicity and urinary bladder cytotoxicity and regenerative hyperplasia induced by arsenite in arsenic (+ 3 oxidation state) methyltransferase knockout mice. A preliminary report. United States. https://doi.org/10.1016/j.taap.2010.04.013
Yokohira, Masanao, Arnold, Lora L, Pennington, Karen L, Suzuki, Shugo, Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Kakiuchi-Kiyota, Satoko, Herbin-Davis, Karen, Thomas, David J, and Cohen, Samuel M., E-mail: scohen@unmc.ed. 2010. "Severe systemic toxicity and urinary bladder cytotoxicity and regenerative hyperplasia induced by arsenite in arsenic (+ 3 oxidation state) methyltransferase knockout mice. A preliminary report". United States. https://doi.org/10.1016/j.taap.2010.04.013.
@article{osti_21460182,
title = {Severe systemic toxicity and urinary bladder cytotoxicity and regenerative hyperplasia induced by arsenite in arsenic (+ 3 oxidation state) methyltransferase knockout mice. A preliminary report},
author = {Yokohira, Masanao and Arnold, Lora L and Pennington, Karen L and Suzuki, Shugo and Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences and Kakiuchi-Kiyota, Satoko and Herbin-Davis, Karen and Thomas, David J and Cohen, Samuel M., E-mail: scohen@unmc.ed},
abstractNote = {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{sup III}). During the first week of As{sup 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{sup 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{sup III} on the bladder epithelium, showing that altered kinetic and dynamic behavior of arsenic can affect its toxicity.},
doi = {10.1016/j.taap.2010.04.013},
url = {https://www.osti.gov/biblio/21460182}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1-2,
volume = 246,
place = {United States},
year = {Thu Jul 15 00:00:00 EDT 2010},
month = {Thu Jul 15 00:00:00 EDT 2010}
}