Zhou Tong, Jia Xiaodong, Chapin Robert E, Maronpot Robert R, Harris Martha W, Liu Jie, Waalkes Michael P, Eddy Edward M
Gamete Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Toxicol Lett. 2004 Dec 30;154(3):191-200. doi: 10.1016/j.toxlet.2004.07.015.
The testes are important targets of cadmium (Cd)-induced toxicity and carcinogenicity in rodents. Exposure to Cd at environmentally relevant low levels is a significant human health concern, but the effects of Cd on the rodent testes at doses that do not cause overt lesions are poorly defined. We used cDNA microarray and quantitative real-time RT-PCR assays to determine gene expression profiles in the testes of CD-1 mice 12-72 h after a single s.c. injection of 5 micromol/kg CdCl2. This dose of Cd did not produce overt histopathological changes, but clearly altered the expression of some genes that are likely to be important in toxicity responses. The most significant changes in gene expression occurred 24 h after treatment, corresponding to when the highest level of Cd was detected in the testes. Increased expression of the C-myc and Egr1 genes strongly suggests acute stress responses. Repressed expression of cell cycle-regulated cyclin B1 and CDC2 proteins indicates a potential for causing G2/M arrest and disturbance of meiosis. Decreased expression of pro-apoptotic genes, particularly Casp3, and DNA repair genes possibly contributes to Cd-induced carcinogenesis. These results indicate that changes in gene expression occur well before overt effects of Cd-induced testicular toxicity and carcinogenicity are apparent.
睾丸是镉（Cd）诱导啮齿动物产生毒性和致癌性的重要靶器官。在环境相关的低水平接触镉是一个重大的人类健康问题，但镉在不引起明显病变剂量下对啮齿动物睾丸的影响却知之甚少。我们使用cDNA微阵列和定量实时RT-PCR分析，来确定单次皮下注射5微摩尔/千克氯化镉后12 - 72小时CD-1小鼠睾丸中的基因表达谱。这个镉剂量并未产生明显的组织病理学变化，但明显改变了一些可能在毒性反应中起重要作用的基因的表达。基因表达的最显著变化发生在处理后24小时，这与在睾丸中检测到最高水平的镉的时间相对应。C-myc和Egr1基因表达增加强烈提示急性应激反应。细胞周期调节蛋白细胞周期蛋白B1和细胞周期蛋白依赖性激酶2（CDC2）蛋白表达受抑制表明可能导致G2/M期阻滞和减数分裂紊乱。促凋亡基因，特别是Casp3，以及DNA修复基因表达降低可能促成镉诱导的致癌作用。这些结果表明，在镉诱导的睾丸毒性和致癌性的明显影响出现之前，基因表达就已经发生了变化。
