Decreased uptake and altered subcellular disposition of testicular cadmium as possible mechanisms of resistance to cadmium-induced testicular necrosis in inbred mice

Mechanisms responsible for resistance to Cd-induced testicular necrosis in inbred mice were investigated using strains resistant (A/J) or susceptible (129/J) to Cd-induced testicular damage. Cadmium accumulation was measured in testes of both strains 15 min, 30 min, 1 h, 2 h, 6 h, 12 h, and 24 h, after intravenous injection of 1 umol 109CdCl2/kg. The subcellular disposition of Cd was determined at 15 min, 6 h and 24 h by fractionation of testicular cytosol on Sephadex G-75 Superfine. Testicular accumulation of Cd was 5-6 times less in A/J mice than in 129/J mice at all time points examined. Gel filtration revealed 4 Cd-binding peaks; in both strains testicular Cd was bound to a protein with a relative molecular mass (Msub(r)) of 30,000 and to metallothionein (MT). The fraction of the total testicular Cd bound to the 30,000 Msub(r) protein was similar in both strains after 15 min (13-18%) and declined rapidly to 5-7% by 6 h. A/J testes had a significantly greater fraction of the total Cd bound to MT both 15 min and 6 h after dosing than 129/J testes (38% vs. 20% at 15 min; 38% vs. 24% at 6 h). By 24 h both strains had approximately 43% of the total testicular Cd bound to MT. The result indicates 2 possible mechanisms of resistance to Cd-induced testicular necrosis in inbred mice: decreased testicular Cd uptake and sequestration of a greater fraction of the tissue Cd by MT. (author)