Low-Dose Cadmium Exposure Reduces Human Prostate Cell Transformation in Culture and Up-Regulates Metallothionein and MT-1G mRNA.
Low-Dose Cadmium Exposure Reduces Human Prostate Cell Transformation in Culture and Up-Regulates Metallothionein and MT-1G mRNA.
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DOI：
10.1080/15401420391434333
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发表时间：
2003-04-01
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影响因子：
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通讯作者：
Jonas, Wayne B
中科院分区：
文献类型：
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作者：
Gaddipati, Jaya P;Rajeshkumar, N V;Jonas, Wayne B
长期低水平接触环境毒素（包括镉 (Cd)）是工业化世界中一个日益严重的问题。防止这些毒素的一种有前景的策略是使用低剂量的环境化学物质暴露来诱导细胞耐受和恢复，这种现象被称为“保护性兴奋效应”。多种系统和多种化学物质都会产生激效[低剂量刺激]效应。镉对啮齿动物来说是一种强效致癌物，也与人类肺癌和前列腺癌有关。在本研究中，我们评估了低剂量和超低剂量长期镉暴露对正常人前列腺细胞 RWPE-1 的保护作用。将细胞暴露于低剂量和超低剂量（0、0（S（-36））、10（-6）、10（-7）、10（-18）、10（-21）、10（-32）或10（-36）M）Cd 20周，然后用10（-5）M Cd处理另外8周。 RWPE-1细胞持续暴露于10(-5)M Cd会导致恶性转化。然而，与对照组相比，用低剂量和超低剂量 Cd 预处理的细胞的转化延迟。此外，预处理细胞中转化细胞堆的数量较低，表明低剂量和超低剂量暴露对高剂量镉诱导的致癌作用具有保护作用。金属硫蛋白 (MT)（主要的镉解毒蛋白）的表达是通过低剂量暴露于镉诱导的，并在 20 周内维持。此外，低剂量和超低剂量 Cd 暴露使 MT-1G mRNA 上调 2 至 3 倍，这可能是该模型中保护性毒物兴奋效应的机制。 MT-1G mRNA 也可能作为极低剂量环境镉暴露的生物指标。
Chronic low-level exposure to environmental toxins, including cadmium (Cd), is a growing problem in the industrialized world. One promising strategy for protection from these toxins is the use of low-dose exposure of environmental chemicals to induce cell tolerance and recovery, a phenomenon known as "protective hormesis". Hormetic [low-dose stimulatory] effects occur in a variety of systems and with a number of chemicals. Cd is a potent carcinogen in rodents and has also been linked to human lung and prostate cancers. In the present study, we have evaluated the protective effects of low and ultra-low dose, long-term Cd exposure in the normal human prostate cells, RWPE-1. Cells were exposed to low and ultra-low doses (0, 0 (S(-36)), 10(-6), 10(-7), 10(-18), 10(-21), 10(-32), or 10(-36)M) of Cd for 20 weeks followed by treatment with 10(-5)M Cd for another 8 weeks. Continuous exposure of RWPE-1 cells to 10(-5)M Cd results in malignant transformation. However, cells pretreated with low and ultra-low doses of Cd had delayed transformation compared with controls. In addition, the number of transformed cell mounds was lower in pretreated cells indicating that low and ultra-low dose exposure had protective effects against high-dose Cd induced carcinogenesis. The expression of metallothionein (MT), the primary Cd detoxification protein, was induced by low-dose exposure to Cd and maintained during the 20 weeks. In addition, MT-1G mRNA was up-regulated 2- to 3-fold by low-dose and ultralow-dose Cd exposures and may be the mechanism of protective hormesis in this model. MT-1G mRNA might also serve as a biological indicator of very low-dose environmental Cd exposure.