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 iv with 10 or 45 mumol 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 (approximately 4 nmol Cd/g tissue). Twenty-four hours later, 129/J testes showed marked interstitial hemorrhage and seminiferous tubule necrosis, while A/J testes showed no microscopic evidence of damage. Two hours postinjection, no histopathologic changes were detected in testes of either strain; however, A/J testes had 15% more Cd associated with the cystosol than 129/J testes, and three times more Cd bound to a 14,500 MW cytosolic protein which had gel filtration and ion-exchange chromatography properties in common with metallothionein (MT). Therefore, resistance of A/J testes to Cd does not appear to be determined solely by decreased Cd accumulation, but is associated with increased binding of testicular Cd to a MT-like protein. However, this increase is 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.
D000818:Animals; D002104:Cadmium / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D002848:Chromatography, DEAE-Cellulose; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D003300:Copper / Q000032:analysis; D004351:Drug Resistance; D005615:Freezing; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008970:Molecular Weight; D051381:Rats; D013054:Spectrophotometry, Atomic; D013347:Subcellular Fractions / Q000032:analysis / Q000378:metabolism; D013737:Testis / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D015032:Zinc / Q000032:analysis
D002104:Cadmium; D003300:Copper; D008668:Metallothionein; D015032:Zinc