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Altered accumulation and subcellular disposition of testicular cadmium in inbred mice resistant to cadmium-induced testicular necrosis

Thesis/Dissertation ·
OSTI ID:5001177
Rodent testis is one of the most sensitive mammalian tissues to the toxic effects of acutely administered Cd. However, numerous inbred mouse strains are resistant to Cd-induced testicular damage, even at lethal Cd doses; the mechanism of this resistance has not been determined. Therefore, testes of mice susceptible (129/J) or resistant (A/J) to Cd-induced damage were examined for possible differences in the accumulation and subcellular disposition of Cd. Twenty-four hours after subcutaneous injection of mice with 30 ..mu..moles CdCl/sub 2//kg, 129/J testes showed extensive interstitial hemorrhage and seminiferous tubule necrosis, while A/J testes appeared histologically normal. Testicular Cd accumulation was 5-6 times less in A/J mice than in 129/J mice at all time points examined. Chromatography of testicular cytosol on Sephadex G-75 Superfine revealed four Cd-binding peaks. Both 15 min and 6 hr after dosing, A/J testes had 14% more of the total tissue Cd bound to the 14,500 MW protein (Cd-BP III), compared to 129/J testes, Cd-BP III behaved like metallothionein during gel filtration and ion exchange chromatography. Additional mice were injected i.v. with 10 (129/J) or 45 (A/J) ..mu..moles CdCl/sub 2//kg to achieve equal testicular Cd concentrations (approx. 4 nmoles Cd/g testis). Twenty-four hours later, 129/J testes were necrotic while A/J testes showed no microscopic evidence of damage. Therefore, resistance of A/J testes to Cd is not determined solely by decreased Cd accumulation, but is associated with increased binding of testicular Cd to Cd-BP III.
Research Organization:
Rochester Univ., NY (USA)
OSTI ID:
5001177
Country of Publication:
United States
Language:
English