Wise Sandra S, Holmes Amie L, Liou Louis, Adam Rosalyn M, Wise John Pierce
Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, Department of Applied Medical Science, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103, USA.
Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, Department of Applied Medical Science, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103, USA; Department of Radiation Oncology, Dana Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, USA.
Toxicol Appl Pharmacol. 2016 Apr 1;296:54-60. doi: 10.1016/j.taap.2016.02.015. Epub 2016 Feb 18.
Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants. However, the impact of hexavalent chromium (Cr(VI)) on bladder cells has not been studied. We compared chromate toxicity in two bladder cell lines; primary human urothelial cells and hTERT-immortalized human urothelial cells. Cr(VI) induced a concentration- and time-dependent increase in chromosome damage in both cell lines, with the hTERT-immortalized cells exhibiting more chromosome damage than the primary cells. Chronic exposure to Cr(VI) also induced a concentration-dependent increase in aneuploid metaphases in both cell lines which was not observed after a 24h exposure. Aneuploidy induction was higher in the hTERT-immortalized cells. When we correct for uptake, Cr(VI) induces a similar amount of chromosome damage and aneuploidy suggesting that the differences in Cr(VI) sensitivity between the two cells lines were due to differences in uptake. The increase in chromosome instability after chronic chromate treatment suggests this may be a mechanism for chromate-induced bladder cancer, specifically, and may be a mechanism for metal-induced bladder cancer, in general.
许多金属是众所周知的人类膀胱致癌物。尽管金属与膀胱癌对职业健康和公众健康有着重大影响，但致癌机制在很大程度上仍不清楚。特别是铬，由于在铬酸盐工人中发现膀胱癌发病率升高，并且对金属髋关节植入患者的关注度也在增加，所以它是一种值得关注的金属。然而，六价铬（Cr(VI)）对膀胱细胞的影响尚未得到研究。我们比较了两种膀胱细胞系（原代人尿道上皮细胞和hTERT永生化人尿道上皮细胞）中的铬酸盐毒性。Cr(VI)在两种细胞系中均诱导了浓度和时间依赖性的染色体损伤增加，其中hTERT永生化细胞比原代细胞表现出更多的染色体损伤。长期暴露于Cr(VI)还在两种细胞系中诱导了浓度依赖性的非整倍体中期增加，而在24小时暴露后未观察到这种情况。hTERT永生化细胞中的非整倍体诱导更高。当我们校正摄取量时，Cr(VI)诱导了相似数量的染色体损伤和非整倍体，这表明两种细胞系之间Cr(VI)敏感性的差异是由于摄取差异所致。长期铬酸盐处理后染色体不稳定性的增加表明，这可能是铬酸盐诱导膀胱癌的一种机制，具体而言，也可能是一般金属诱导膀胱癌的一种机制。
