US EPA

744868 

Journal Article 

Abstract 

Malignant transformation of human urothelial cells by arsenite and cadmium 

Somji, S; Gurel, V; Park, S; Sens, M; Garrett, SH; Sens, DA 

2004 

1 

Toxicologist
ISSN: 0731-9193 

TOX/4001018 

78 

1-S 

155 

eng 

Cadmium and arsenite are human carcinogens and exposure to either of them has been associated with the development of bladder cancer. Neither cadmium or arsenite has been shown to elicit the malignant transformation of human urothelial cells under in vitro conditions, although such a model would be of value in elucidating the mechanism of carcinogenesis of both compounds. This laboratory has characterized an immortalized cell culture model of human urothelial cells (UROtsa) that does not form colonies in soft agar or produce tumor growth in nude mice. The goal of the present study was to determine if exposure of UROtsa cells to cadmium or arsenite would result in malignant transformation. UROtsa cells were grown on both serum-free and serum-containing growth medium to confluency and then exposed to cadmium and arsenite concentrations that produced greater than 90% cell death over a 30 to 60 day period. Surviving cells were allowed to grow back to confluency in the continued presence of cadmium or arsenite. At passage 4, 8, 12 and 16, the cultures were tested for their ability to form colonies in soft agar. At passage 4 and 8 no colonies were formed, at passage 12 a few colonies were formed, and at passage 16 a large number of colonies were formed in the soft agar assay. Cells at passage 16 from each treatment group were injected into nude mice and all 4 groups formed tumors. Control UROtsa cells of equal passage failed to form colonies in soft agar and did not form tumors in nude mice. Histological examination of the tumors demonstrated characteristics expected of transitional cell carcinoma of the bladder. Tumors produced from cells grown in serum tended to have features associated with high grade tumors while those from serum-free cells had features associated with low grade tumors. These studies show that both cadmium and arsenite can cause malignant transformation of human urothelial cells. 

Society of Toxicology Annual Meeting