Wahba Z Z, Waalkes M P
Division of Cancer Etiology, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702.
Fundam Appl Toxicol. 1990 Nov;15(4):641-50. doi: 10.1016/0272-0590(90)90181-i.
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.
最近的研究表明，低剂量镉预处理可预防镉诱导的睾丸间质细胞瘤（TIC）。然而，低剂量镉诱导这种耐受性的机制尚不清楚。因此，在本研究中，我们评估了体内镉预处理（3 μmol/kg）对体外暴露于镉的分离TICs的镉摄取、细胞毒性、金属含量（锌、钾和钙）以及低分子量睾丸镉结合蛋白（低Mr TC-BPs）的影响。通过胶原酶分散Wistar（WF/NCr）大鼠睾丸分离TICs，并与镉（1.0 mM）孵育15至60分钟。与镉孵育1小时后，体内镉预处理使体外镉摄取降低了24%。体内镉预处理还导致体外镉诱导的细胞毒性显著降低，这表现为细胞内钾、谷草转氨酶损失减少，脂质过氧化减少，以及体外镉诱导的钙流入TICs减少。这些细胞毒性作用并非仅仅归因于细胞死亡，因为即使在体外镉暴露1小时后，TIC的活力仍然很高。通过细胞乳酸脱氢酶活性评估，镉诱导的细胞间酶抑制也因低剂量镉预处理而降低。镉预处理未改变锌、钙或钾的基础水平。通过电泳评估，低剂量体内镉预处理和体外镉暴露似乎都未显著改变低Mr TCBPs的水平。体内锌预处理也能有效抑制镉诱导的睾丸肿瘤，它能使TICs中镉诱导的细胞毒性产生类似程度的降低。这表明，导致镉诱导的TIC肿瘤减少的处理方法始终能够降低体外分离的TICs中镉诱导的细胞毒性。
