Studies on combined effects of low-dose cadmium and environmental chemicals

镉（Cd）是一种潜在的环境危害，可引起多种器官的疾病。在这项研究中，我们研究了参与适应性反应镉诱导的人骨髓单核细胞淋巴瘤U937细胞凋亡的分子机制。50μM氯化镉（CdCl 2）处理U937细胞12 h后，细胞发生明显凋亡。这与细胞内活性氧（ROS）的增加、JNK的持续磷酸化、半胱天冬酶-3的活化、Mcl-1（抗凋亡Bcl-2蛋白）的减少以及Bim、Noxa和tBid（Bcl-2家族下的促凋亡蛋白）的增加相关。1μM CdCl 2处理72 h，细胞无凋亡发生。然而，低剂量CdCl 2预处理显著改变了细胞对50μM CdCl 2的敏感性，并抑制了细胞凋亡。与此同时，细胞内ROS的产生和JNK的活化显着减少。1μM CdCl 2预处理也可减弱50μM CdCl 2引起的Mcl-1的降低和Bim、Noxa和tBid的升高。暴露于低剂量镉后细胞凋亡的抑制表明了一种潜在的机制，这可能有助于解释为什么长期暴露于低剂量镉的人患某些癌症的风险增加。

Cadmium(Cd) is a potential environmental hazard that induces disorders in various organs. In this study, we examined the molecular mechanisms involved in the adaptive response to Cd-induced apoptosis in human myelomonocytic lymphoma U937 cells. When U937 cells were treated with 50μM cadmium chloride(CdCl2) for 12 hours, significant apoptosis occurred. This was associated with an increase in intracellular reactive oxygen species(ROS), sustained phosphorylation of JNK, activation of caspase-3, a decrease in Mcl-1(anti-apoptotic Bcl-2 proteins), and increases in Bim, Noxa and tBid(a pro-apoptotic protein under the Bcl-2 family). No apoptosis occurred when the cells were treated with 1μM CdCl2 for 72 hours. However, pretreatment with low-dose CdCl2 dramatically altered the sensitivity of the cells to 50μM CdCl2 with inhibition of apoptosis. Concomitantly, there were significant decreases in the generation of intracellular ROS and the activation of JNK. Pretreatment with 1μM CdCl2 also attenuated the decrease in Mcl-1 and the increases in Bim, Noxa and tBid induced by 50μM CdCl2. The inhibition of apoptosis following exposure to low-dose Cd suggests a potential mechanism that may help explain why people exposed to low doses of Cd for a long time have an increased risk of developing certain cancers.