金属硫蛋白基因亚型表达在镉接触中作为生物标志物的研究

目的探讨人外周血淋巴细胞（HPBIs）中金属硫蛋白（MT）基因业型的表达在镉接触中作为生物标志物的可行性。方法选择职业接触镉的人群，进行接触评定和效应评定，分离淋巴细胞，用RT-PCR测定MT基因亚型的表达水平。结果接触组工人的MT-1A、1E、1F、1X和MT-2A mRNA表达水平明显高于对照组，差异有统计学意义（P〈0．05）。随血镉水平增高，MT-1A1E、1F、1X和MT-2A mRNA表达水平都明显增高（P〈0．05）。随尿镉水平增高，MT-1A、1E、1F、1X和MT-2A mRNA表达水平有升高趋势，且MT-1A和MT-2A mRNA表达水平明显升高（P〈0．05）。MT-1A、1E、1F、1X和MT-2A mRNA表达水平与血镉水平明显相关（P〈0．05），同时MT-1A、1F、MT-2A mRNA表达水平与尿镉水平明显相关（P〈0．05）。血镉与MT-1E、MT-1F、MT-1X、MT-2A mRNA基础表达水平存在剂量-效应关系；血镉、β2-MG和尿金属硫蛋白（UMT）与MT-1A基础表达水平存在剂量-效应关系。结论HPBLs中MT基因亚型的表达可作为镉接触性生物标志物，其中MT-1A还可作为镉致肾毒性的效应性生物标志物。

Application of Metallothionein Gene Isoforms Expression as Biomarkers in Cadmium Exposure

OBJECTIVE: To investigate the feasibility of metallothionein (MT) gene expression level in human peripheral blood lymphocytes (HPBLs) as a biomarker in cadmium exposure. METHODS: The MT gene expression level in HPBLs of workers exposed to cadmium was examined using RT-PCR technique, and the exposure assessment and effect assessment were conducted in exposed workers. RESULTS: The basal MT-1A, IE, IF, IX and MT-2A expression level in workers exposed to cadmium were significantly higher than those in the control group (P < 0.05). The basal MT-1A, IE, IF, IX and MT-2A expression level would be significantly increased with the increase of the blood cadmium (BCd) level (P < 0.05). There was a trend of increase for the mRNA expression of the basal MT-1A, 1E, IF, IX, MT-2A, especially for the mRNA expression of MT-1A and MT-2A (P < 0.05) with the increase of the level of the urine cadmium (UCd). There was a good dose-response relationship between basal MT-1A expression and UCd. The basal MT-1A, IE, IF, IX and MT-2A expression level were significantly correlated with BCd (P < 0.05) while the basal MT-1A, IF and MT-2A expression level were significantly correlated with UCd (P < 0.05). There were dose-effect relationships of BCd to the basal MT-1E, MT-1F, MT-1X and MT-2X expression level respectively and there were also dose-effect relationships of UCd, beta(2)-MG and the urine metallothionein to the basal MT-1A expression. CONCLUSION: The expression of the MT gene isoforms in HPBLs can serve as the biomarker for the cadmium exposure and MT-1A can also serve as the effective biomarkers for the cadmium-induced renal toxicity.