Effect of in vivo low-dose cadmium pretreatment on the in vitro interactions of cadmium with isolated interstitial cells of the rat testes.
Recent studies have shown that Cd-induced testicular interstitial cell (TIC) tumors can be prevented by low-dose Cd pretreatment. However, the mechanism by which low-dose Cd induces such tolerance is unclear. Thus, in this study we assessed the effects of in vivo Cd pretreatment (3 mumol/kg) on Cd uptake, cytotoxicity, metal content (Zn, K, and Ca), and low molecular weight testicular Cd-binding proteins (low Mr TC-BPs) of isolated TICs exposed to Cd in vitro. TICs were isolated by collagenase dispersion of Wistar (WF/NCr) rat testes and incubated with Cd (1.0 mM) for 15 to 60 min. In vivo Cd pretreatment decreased in vitro Cd uptake by 24% after 1 hr of incubation with Cd. In vivo Cd pretreatment also resulted in a marked reduction of in vitro Cd-induced cytotoxicity, as reflected by reduced loss of cellular K, glutamic-oxaloacetic transaminase, as well as reduced lipid peroxidation and decreased Cd-induced Ca influx into TICs in vitro. These cytotoxic effects were not attributed solely to cell death as TIC viability remained high even after 1 hr of in vitro Cd exposure. Cd-induced inhibition of intercellular enzymes, as assessed by cellular lactate dehydrogenase activity, was also reduced by low-dose Cd pretreatment. Cd pretreatment did not alter basal levels of Zn, Ca, or K. Neither low-dose in vivo Cd pretreatment nor in vitro Cd exposure appeared to greatly alter levels of the low Mr TCBPs as assessed by electrophoresis. In vivo Zn pretreatment, which also effectively inhibits Cd-induced testicular tumors, results in a similar reduction in Cd-induced cytotoxicity in TICs. This indicates that treatments which result in reduced Cd-induced TIC tumors are consistently capable of reducing Cd-induced cytotoxicity in isolated TICs in vitro.
Wahba
Z Z
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Division of Cancer Etiology, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702.
Waalkes
M P
MP
D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002104:Cadmium / Q000032:analysis / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002850:Chromatography, Gel; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D008670:Metals / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D008670:Metals; C004203:cadmium-binding protein; D002104:Cadmium; D008668:Metallothionein; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D011188:Potassium