RESISTANCE TO CADMIUM-INDUCED NECROSIS IN TESTES OF INBRED MICE - POSSIBLE ROLE OF A METALLOTHIONEIN-LIKE CADMIUM-BINDING PROTEIN

Altered accumulation and subcellular disposition of testicular Cd were examined as possible explanations for the resistance to Cd-induced testicular damage observed in certain inbred strains of mice. Mouse strains susceptible (129/J) or resistant (A/J) to Cd-induced testicular necrosis were injected i.v. with 10 or 45 .mu.mol CdCl2/kg, respectively. This dosing regimen compensated for decreased Cd accumulation by A/J testes and established similar concentrations of Cd in testes of both strains (.apprx. 4 nmol Cd/g tissue). Twenty four h later, 129/J testes showed marked interstitial hemorrhage and seminiferous tubule necrosis, while A/J testes showed no microscopic evidence of damage. Two h postinjection, no histopathologic changes were detected in testes of either strain; A/J testes had 15% more Cd associated with the cystosol than 129/J testes, and 3-fold more Cd bound to a 14,500 MW cystolic protein which had gel filtration and ion-exchange chromatography properties in common with metallothionein (MT). Resistance of A/J testes to Cd probably was not determined solely by decreased Cd accumulation, but was associated with increased binding of testicular Cd to a MT-like protein. This increase was not accompanied by a proportional increase in the total Cd-binding capacity of the MT-like protein in A/J testes compared to 129/J testes.