DMAV in Drinking Water Activated NF-κB Signal Pathway and Increased TGF-β and IL-1β Expressions in Bladder Epithelial Cells of Rats

Dimethylarsinic acid (DMA(V)) is the main product of arsenic methylation metabolism in vivo and is rat bladder carcinogen and tumor promoting agent. In this study, we measured the expressions of mRNA and proteins of NF-kappa B pathway members, IKK alpha, IKK beta, p65, and p50 in rat bladder epithelium by qRT-PCR and immunohistochemical analysis after rats received drinking water containing 100 and 200 ppm DMA(V) for 10 weeks. Transforming growth factor-beta (TGF-beta) immunoexpression in rat bladder epithelium and urine level of IL-1 beta also were determined. We found that DMA(V) dramatically increased the mRNA levels of NF-kappa B p50 and IKK alpha in the bladder epithelium of rats compared to the control group. Immunohistochemical examinations showed that DMA(V) increased immunoreactivities of IKK alpha, IKK beta, and phospho-NF-kappa B p50 in the cytoplasm and phospho-NF-kappa B p50 and p65 in nucleus of rat urothelial cells. In addition, DMA(V) treated rats exhibited significantly increased inflammatory factor TGF-beta immunoreactivity in bladder epithelium and IL-1 beta secretion in urine. These data suggest that DMA(V) could activate NF-kappa B signal pathway and increase TGF-beta and IL-1 beta expressions in bladder epithelial cells of rats.