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Title: A comparative study of the sub-chronic toxic effects of three organic arsenical compounds on the urothelium in F344 rats; gender-based differences in response

Abstract

Epidemiological studies indicated that human arsenic exposure can induce urinary bladder cancer. Methylation of inorganic arsenic can generate more reactive and toxic organic arsenical species. In this regard, it was recently reported that the methylated arsenical metabolite, dimethylarsinic acid [DMA(V)], induced urinary bladder tumors in rats. However, other methylated metabolites, like monomethylarsonic acid [MMA(V)] and trimethylarsine oxide (TMAO) were not carcinogenic to the urinary bladder. In order to compare the early effects of DMA(V), MMA(V), and TMAO on the urinary bladder transitional cell epithelium at the scanning electron microscope (SEM) level, we investigated the sub-chronic (13 weeks) toxicological effects of MMA(V) (187 ppm), DMA(V) (184 ppm), TMAO (182 ppm) given in the drinking water to male and female F344 rats with a focus on the urinary bladder in this study. Obvious pathological changes, including ropy microridges, pitting, increased separation of epithelial cells, exfoliation, and necrosis, were found in the urinary bladders of both sexes, but particularly in females receiving carcinogenic doses of DMA(V). Urine arsenical metabolic differences were found between males and females, with levels of MMA(III), a potential genotoxic form, higher in females treated with DMA(V) than in males. Thus, this study provides clear evidence that DMA(V) is moremore » toxic to the female urinary bladder, in accord with sensitivity to carcinogenesis. Important gender-related metabolic differences including enhanced presentation of MMA(III) to the urothelial cells might possibly account for heightened sensitivity in females. However, the potential carcinogenic effects of MMA(III) need to be further elucidated.« less

Authors:
 [1];  [1];  [2];  [1];  [1];  [3];  [3];  [1]
  1. Department of Pathology, Osaka City University Medical School, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan)
  2. Laboratory of Comparative Carcinogenesis, National Cancer Institute (NCI/NIH) at NIEHS, Research Triangle Park, NC 27709-2233 (United States)
  3. Department of Preventive Medicine and Environmental Health, Osaka City University Medical School, Osaka 545-8585 (Japan)
Publication Date:
OSTI Identifier:
20783416
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 210; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2005.04.018; PII: S0041-008X(05)00190-0; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALKALINE PHOSPHATASE; AMINOTRANSFERASES; ARSENIC; BLADDER; BLOOD CELLS; CARCINOGENESIS; DRINKING WATER; EPITHELIUM; ICP MASS SPECTROSCOPY; ION EXCHANGE CHROMATOGRAPHY; METHYLATION; NECROSIS; NEOPLASMS; OXIDES; RATS; SCANNING ELECTRON MICROSCOPY; SENSITIVITY; TOXICITY; URINE

Citation Formats

Shen, Jun, Wanibuchi, Hideki, Waalkes, Michael P, Salim, Elsayed I, Kinoshita, Anna, Yoshida, Kaoru, Endo, Ginji, and Fukushima, Shoji. A comparative study of the sub-chronic toxic effects of three organic arsenical compounds on the urothelium in F344 rats; gender-based differences in response. United States: N. p., 2006. Web. doi:10.1016/j.taap.2005.04.018.
Shen, Jun, Wanibuchi, Hideki, Waalkes, Michael P, Salim, Elsayed I, Kinoshita, Anna, Yoshida, Kaoru, Endo, Ginji, & Fukushima, Shoji. A comparative study of the sub-chronic toxic effects of three organic arsenical compounds on the urothelium in F344 rats; gender-based differences in response. United States. https://doi.org/10.1016/j.taap.2005.04.018
Shen, Jun, Wanibuchi, Hideki, Waalkes, Michael P, Salim, Elsayed I, Kinoshita, Anna, Yoshida, Kaoru, Endo, Ginji, and Fukushima, Shoji. 2006. "A comparative study of the sub-chronic toxic effects of three organic arsenical compounds on the urothelium in F344 rats; gender-based differences in response". United States. https://doi.org/10.1016/j.taap.2005.04.018.
@article{osti_20783416,
title = {A comparative study of the sub-chronic toxic effects of three organic arsenical compounds on the urothelium in F344 rats; gender-based differences in response},
author = {Shen, Jun and Wanibuchi, Hideki and Waalkes, Michael P and Salim, Elsayed I and Kinoshita, Anna and Yoshida, Kaoru and Endo, Ginji and Fukushima, Shoji},
abstractNote = {Epidemiological studies indicated that human arsenic exposure can induce urinary bladder cancer. Methylation of inorganic arsenic can generate more reactive and toxic organic arsenical species. In this regard, it was recently reported that the methylated arsenical metabolite, dimethylarsinic acid [DMA(V)], induced urinary bladder tumors in rats. However, other methylated metabolites, like monomethylarsonic acid [MMA(V)] and trimethylarsine oxide (TMAO) were not carcinogenic to the urinary bladder. In order to compare the early effects of DMA(V), MMA(V), and TMAO on the urinary bladder transitional cell epithelium at the scanning electron microscope (SEM) level, we investigated the sub-chronic (13 weeks) toxicological effects of MMA(V) (187 ppm), DMA(V) (184 ppm), TMAO (182 ppm) given in the drinking water to male and female F344 rats with a focus on the urinary bladder in this study. Obvious pathological changes, including ropy microridges, pitting, increased separation of epithelial cells, exfoliation, and necrosis, were found in the urinary bladders of both sexes, but particularly in females receiving carcinogenic doses of DMA(V). Urine arsenical metabolic differences were found between males and females, with levels of MMA(III), a potential genotoxic form, higher in females treated with DMA(V) than in males. Thus, this study provides clear evidence that DMA(V) is more toxic to the female urinary bladder, in accord with sensitivity to carcinogenesis. Important gender-related metabolic differences including enhanced presentation of MMA(III) to the urothelial cells might possibly account for heightened sensitivity in females. However, the potential carcinogenic effects of MMA(III) need to be further elucidated.},
doi = {10.1016/j.taap.2005.04.018},
url = {https://www.osti.gov/biblio/20783416}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 210,
place = {United States},
year = {Wed Feb 01 00:00:00 EST 2006},
month = {Wed Feb 01 00:00:00 EST 2006}
}