Effects of zinc on the distribution and toxicity of cadmium in isolated interstitial cells of the rat testis.
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.
Koizumi
T
T
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Waalkes
M P
MP
D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002104:Cadmium / Q000493:pharmacokinetics / Q000633:toxicity*; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
D002104:Cadmium; D001219:Aspartate Aminotransferases; D015032:Zinc; D011188:Potassium