Dimethylarsinic acid (DMA(V) ) changed the expressions of proliferative related factors and secretion of inflammatory cytokines in rat bladder.
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.
Department of Occupational and Environmental Health, Liaoning Provincial Key Lab of Arsenic Biological Effect and Poisoning, School of Public Health, China Medical University, No. 92 Bei Er Road, Heping District, Shenyang, 110001, China.
Zhang
Z
Lin
Liu
L
Shengnan
Wang
W
Fei
Song
S
Yingli
Sun
S
Qingshan
Sheng
S
Wei
Xi
X
Shuhua
Sun
S
Guifan
D000818:Animals; D002101:Cacodylic Acid / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000652:urine; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
D016207:Cytokines; D015850:Interleukin-6; D018809:Proliferating Cell Nuclear Antigen; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D019938:Cyclin D1; D002101:Cacodylic Acid; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat
bladder; dimethylarsinic acid; inflammation; proliferation; rats; ultrastructure