Dimethylarsinic acid (DMAV) changed the expressions of proliferative related factors and secretion of inflammatory cytokines in rat bladder
Version of Record online: 15 MAY 2014
Copyright © 2014 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 35, Issue 2, pages 133–141, February 2015
How to Cite
2015), Dimethylarsinic acid (DMAV) changed the expressions of proliferative related factors and secretion of inflammatory cytokines in rat bladder, Journal of Applied Toxicology, 35, pages 133–141. DOI: 10.1002/jat.3001, , , , , , , and (
- Issue online: 22 DEC 2014
- Version of Record online: 15 MAY 2014
- Manuscript Accepted: 8 FEB 2014
- Manuscript Revised: 2 FEB 2014
- Manuscript Received: 22 DEC 2013
- National Natural Science Foundation of China (NSFC). Grant Number: 81072244 and 81373023
- dimethylarsinic acid;
Dimethylarsinic acid (DMAV), the major urinary metabolite of inorganic arsenic, is a urinary bladder carcinogen and bladder tumor promoter in adult rats. Increased urothelial cellular proliferation has been considered as an earlier phenotype in DMAV-induced bladder carcinogenesis. The present study examined the ultrastructural changes of bladder epithelial cells and expressions of proliferation factors, as well as the secretion of inflammatory cytokines in rats exposed to DMAV for 10 weeks by transmission electron microscopy (TEM), qRT-PCR, immunohistochemical staining and ELISA methods. The results showed that DMAV administered in the drinking water produced urothelial cytotoxicity and ultrastructural changes in rats. PCNA, cyclin D1 and COX-2 mRNA expressions and immunoreactivities were elevated in bladder urothelium. In addition, 200 ppm DMAV treatment increased the transforming growth factor-beta 1 (TGF-β1) secretion and decreased tumor necrosis factor-alpha (TNF)-α level in the urine of rats. These data suggest that chronic inflammation, bladder epithelium lesions and proliferation might be the basic process of the chronic toxicity effects in DMAV-treated rats. Copyright © 2014 John Wiley & Sons, Ltd.