Involvement of sulfhydryl metabolism in tolerance to cadmium in testicular cells.
Cadmium (Cd)-induced acute testicular toxicity and testicular interstitial cell (IC) tumors can be prevented by low-dose Cd pretreatment. The mechanism of this self-tolerance is unknown. In this regard glutathione (GSH) may play a role in protecting cells from damage by Cd. Therefore, possible mechanisms of self tolerance to Cd in ICs were investigated with emphasis on sulfhydryl metabolism. Rats were pretreated with low-dose Cd (3.0 mumol/kg, sc). Such low-dose Cd pretreatment prevented the necrotizing effects of normally testopathic doses of Cd (20.0 mumol/kg, sc) given 24 hr later. ICs were isolated by collagenase dispersion 24 hr after pretreatment and incubated with Cd (1.0 mM) for 1 hr. In vivo Cd-pretreatment alone increased GSH levels (as determined by HPLC) of whole cells (17%) and cytosol (17%) compared to nonpretreated control. When ICs from nonpretreated rats were exposed to Cd in vitro, GSH in whole cells declined 8% compared to nonpretreated control and 21% compared to cells from in vivo Cd-pretreated rats. In ICs isolated from pretreated rats and exposed to Cd in vitro, GSH levels were normal in whole cells and slightly increased in cytosol. In whole testes low-dose Cd reduced GSH overall, both in cytosol (34%) and in nuclei (14%). Changes in cysteine levels were also seen, similar to those of GSH in whole ICs and cytosol. Neither low-dose in vivo Cd-pretreatment nor in vitro Cd exposure greatly altered levels of the low Mr testicular Cd-binding proteins as assessed by electrophoresis. These results indicate that sulfhydryl metabolism, specifically increased GSH, may be a factor in self tolerance to Cd in ICs.
Wahba
Z Z
ZZ
Division of Cancer Etiology, National Cancer Institute, Frederick Cancer Research Facility, Maryland 21701.
Hernandez
L
L
Issaq
H J
HJ
Waalkes
M P
MP
D000818:Animals; D002104:Cadmium / Q000378:metabolism / Q000633:toxicity*; D002850:Chromatography, Gel; D003545:Cysteine / Q000378:metabolism; D003600:Cytosol / Q000032:analysis; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D004591:Electrophoresis, Polyacrylamide Gel; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D013997:Time Factors
D013438:Sulfhydryl Compounds; C004203:cadmium-binding protein; D002104:Cadmium; D008668:Metallothionein; D005978:Glutathione; D003545:Cysteine