Dimethylarsinic acid (DMA(V) ) changed the expressions of proliferative related factors and secretion of inflammatory cytokines in rat bladder.

Abstract

Dimethylarsinic acid (DMA(V) ), 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 DMA(V) -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 DMA(V) for 10 weeks by transmission electron microscopy (TEM), qRT-PCR, immunohistochemical staining and ELISA methods. The results showed that DMA(V) 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 DMA(V) 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 DMA(V) -treated rats.

• Authors: Zhang Lin, Liu Shengnan, Wang Fei, Song Yingli, Sun Qingshan, Sheng Wei, Xi Shuhua, Sun Guifan
• Journal: Journal of applied toxicology : JAT (J Appl Toxicol) Vol. 35 Issue 2 Pg. 133-41 (Feb 2015) ISSN: 1099-1263 [Electronic] England
• PMID: 24832369 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 John Wiley & Sons, Ltd.

Chemical References

• Cytokines
• Interleukin-6
• Proliferating Cell Nuclear Antigen
• Transforming Growth Factor beta
• Tumor Necrosis Factor-alpha
• Cyclin D1
• Cacodylic Acid
• Cyclooxygenase 2
• Ptgs2 protein, rat

Topics

• Animals
• Cacodylic Acid (toxicity)
• Cell Proliferation (drug effects)
• Cyclin D1 (biosynthesis)
• Cyclooxygenase 2 (biosynthesis)
• Cytokines (biosynthesis, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Female
• Inflammation (chemically induced, metabolism)
• Interleukin-6 (biosynthesis, metabolism)
• Male
• Microscopy, Electron, Transmission
• Proliferating Cell Nuclear Antigen (biosynthesis)
• Rats
• Rats, Wistar
• Reverse Transcriptase Polymerase Chain Reaction
• Transforming Growth Factor beta (biosynthesis, metabolism)
• Tumor Necrosis Factor-alpha (urine)
• Urinary Bladder (drug effects, metabolism, ultrastructure)
• Urinary Bladder Neoplasms (chemically induced)
• Urothelium (drug effects, metabolism, ultrastructure)