Arsenic in drinking water has been linked with an increased risk of bladder cancer. I wanted to find out whether bladder cancer can be induced or not after treatment with BBN and/or arsenic in mice bladder also to observe the efficient gene/protein expression changes which may involve in cancer in mice and in human urothelium. In my experiments, I designed 2 animal model and 1 human cell line study. In 1st model, 60 C57BL/6 female mice were involved and divided into 6 groups: control, BBN, DMA, NaAsO2, BBN and DMA, BBN and NaAsO2.Chemicals were administered to mice with drinking water for 20 weeks within 5 groups. In 2nd model, another 60C57BL/6 male mice were included and treated by BBN for 6weeks then used NaAsO2 and continued for total 26 weeks. They were also divided into 6 groups: control, BBN 6 weeks, BBN 6 weeks and water 20 weeks, BBN 6 weeks and10 ppm NaAsO2 20 weeks, BBN 6 weeks and100 ppm NaAsO2 20 weeks. In human cell line study, SV-HUC1 was treated with DMA and NaAsO2 in different dose for 8 weeks. In histological data we have seen DMA and NaAsO2 alone treatment showed normal bladders. But BBN and DMA caused 30 % urothelial carcinoma superficially invasive bladder tumor and NaAsO2 with BBN also caused 10 % urothelial carcinoma superficially invasive and 10 % deeply invasive bladder tumor in female mice. In Western blot of mice bladder tissue,GSTM1, p21 and NQO1 proteins expression were down-regulated whereas Sp1 and GSTO1 protein expressions were up regulated with BBN and with their combination. In histological data we have seen, NaAsO2 with BBN pretreatment can cause 10 % urothelial carsinoma deeply invasive whereas NaAsO2alone also caused 10 % high grade dysplasia and 40 % papilloma in male mice bladders.From cell line data, after treated with 100 µM DMA, 0.05 or 0.1 µM NaAsO2 to SV-HUC1 for 10 weeks, found that DMA and NaAsO2 accelerated cell migration and proliferation ability. Also observed, GSTM1 and connecxin-43 mRNA expression remains slightly down regulated after long term treatment with DMA and NaAsO2 to SV-HUC1.Accordingly, the results from this study propose that after longtime exposure to high dose NaAsO2 in drinking water, cancer can be induced in mice bladder tissue. These studies also reveal that after long term treatment with DMA and NaAsO2 to SV-HUC1 accelerated cell migration and proliferation ability. In summary, inorganic arsenic alone is indeed a carcinogen of bladder cancer.
