Sens Donald A, Park Seongmi, Gurel Volkan, Sens Mary Ann, Garrett Scott H, Somji Seema
Department of Surgery, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota 58202, USA.
Toxicol Sci. 2004 May;79(1):56-63. doi: 10.1093/toxsci/kfh086. Epub 2004 Feb 19.
Arsenic and cadmium (Cd(+2)) are human carcinogens, and epidemiological studies have implicated both pollutants in the development of urinary bladder cancer. Despite this epidemiological base, it is unknown if either Cd(+2) or arsenite (As(+3)) can directly cause the malignant transformation of human urothelial cells. The goal of this study was to determine if Cd(+2) and/or As(+3) are able to cause the malignant transformation of human urothelial cells. The strategy employed was to expose the nontumorigenic urothelial cell line UROtsa to long-term in vitro exposure to Cd(+2) and As(+3), with the endpoint being the ability of the cells to form colonies in soft agar and tumors when heterotransplanted into nude mice. It was demonstrated that a long-term exposure to either 1 M Cd(+2) or 1 M As(+3) resulted in the selection of cells that were able to form colonies in soft agar and tumors when heterotransplanted into nude mice. The histology of the tumor heterotransplants produced by UROtsa cells malignantly transformed by Cd(+2) had epithelial features consistent with those of a classic transitional-cell carcinoma of the bladder. The histology of the tumor heterotransplants produced by cells malignantly transformed by As(+3) was unique in that the cells displayed a prominent squamoid differentiation.
砷和镉（Cd(+2)）是人类致癌物，流行病学研究表明这两种污染物都与膀胱癌的发生有关。尽管有这样的流行病学依据，但尚不清楚Cd(+2)或亚砷酸盐（As(+3)）是否能直接导致人尿道上皮细胞的恶性转化。本研究的目的是确定Cd(+2)和/或As(+3)是否能够导致人尿道上皮细胞的恶性转化。采用的策略是将非致瘤性尿道上皮细胞系UROtsa长期体外暴露于Cd(+2)和As(+3)，终点指标是细胞在软琼脂中形成集落的能力以及异种移植到裸鼠体内后形成肿瘤的能力。结果表明，长期暴露于1 M Cd(+2)或1 M As(+3)会导致选择出的细胞在异种移植到裸鼠体内时能够在软琼脂中形成集落并形成肿瘤。由Cd(+2)恶性转化的UROtsa细胞产生的肿瘤异种移植的组织学特征与经典膀胱移行细胞癌的上皮特征一致。由As(+3)恶性转化的细胞产生的肿瘤异种移植的组织学特征独特，因为这些细胞表现出明显的鳞状分化。
