Koizumi T, Waalkes M P
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Toxicology. 1989 Jun 1;56(2):137-46. doi: 10.1016/0300-483x(89)90128-5.
To investigate mechanisms by which zinc prevents cadmium carcinogenicity in the rat testis, the effect of in vivo zinc pretreatment on the distribution, influx, efflux and in vitro cytotoxicity of cadmium in isolated testicular interstitial cells was studied. Zinc pretreatment resulted in marked reduction of cadmium-induced cytotoxicity, as reflected by reduced loss of both intracellular K and glutamic-oxaloacetic transaminase (GOT) from interstitial cells. The subcellular distribution of cadmium was also altered in zinc pretreated cells, with a major shift of cadmium away from the nuclei to other subcellular components such as mitochondria, microsomes and cytosol. In vitro cadmium accumulation in isolated nuclei was also decreased by in vivo zinc pretreatment. In vivo zinc pretreatment also greatly enhanced both influx and efflux of cadmium. These results suggest that a major preventive effect of zinc against cadmium-induced testicular tumors may be due to its ability to reduce the cytotoxicity of cadmium in interstitial cells by enhancing efflux of cadmium and decreasing accumulation of cadmium in nuclei of this target cell population.
为研究锌预防大鼠睾丸中镉致癌作用的机制，研究了体内锌预处理对镉在分离的睾丸间质细胞中的分布、流入、流出及体外细胞毒性的影响。锌预处理导致镉诱导的细胞毒性显著降低，这表现为间质细胞内钾和谷草转氨酶（GOT）损失减少。镉在亚细胞水平的分布在锌预处理的细胞中也发生了改变，镉从细胞核大量转移到其他亚细胞成分，如线粒体、微粒体和胞质溶胶。体内锌预处理还降低了体外分离细胞核中镉的积累。体内锌预处理还极大地增强了镉的流入和流出。这些结果表明，锌对镉诱导的睾丸肿瘤的主要预防作用可能是由于其通过增强镉的流出并减少镉在该靶细胞群体细胞核中的积累来降低镉在间质细胞中的细胞毒性的能力。
