Interactions of cadmium with rat testicular interstitial cell nuclei: Alterations induced by zinc pretreatment and cadmium binding proteins.
To help elucidate the mechanism by which zinc prevents cadmium-induced interstitial cell (IC) tumour formation in the rat, the subcellular distribution of cadmium in isolated ICs was studied. In both isolated intact cells and in isolated nuclei, in vivo zinc pretreatment reduced the nuclear uptake of cadmium and resulted in a decreased accumulation of cadmium in subnuclear components, including chromatic and DNA. In intact cells, in vivo zinc pretreatment increased cadmium retention in mitochondria. microsomes and cytosol. An increase in the metal content in three major cytosolic cadmium-binding fractions was also seen, including the low-molecular-weight testicular cadmium-binding protein (TCBP) previously shown to differ from metallothionein. Uptake of cadmium in association with purified TCBP into isolated IC nuclei was about double that of cadmium bound to purified hepatic metallothionein. These data suggest that zinc may prevent IC tumour formation by reducing cadmium accumulation in nuclei and subnuclear components, including chromatin and DNA. This appears to be through a direct inhibition of cadmium uptake by zinc pretreatment at the nuclear membrane and also indirectly by an enhanced retention of cadmium in non-nuclear subcellular components. These data also indicate that the absence of metallothionein in ICs may render this cell population vulnerable to cadmium by allowing increased nuclear uptake.
Koizumi
T
T
Faculty of Pharmaceutical Sciences, Chiba University, 1-33, Yayoi-cho, Chiba 260, Japan.
Waalkes
M P
MP