Wahba Z Z, Hernandez L, Issaq H J, Waalkes M P
Division of Cancer Etiology, National Cancer Institute, Frederick Cancer Research Facility, Maryland 21701.
Toxicol Appl Pharmacol. 1990 Jun 1;104(1):157-66. doi: 10.1016/0041-008x(90)90291-2.
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.
低剂量镉预处理可预防镉（Cd）诱导的急性睾丸毒性和睾丸间质细胞瘤。这种自身耐受性的机制尚不清楚。在这方面，谷胱甘肽（GSH）可能在保护细胞免受镉损伤方面发挥作用。因此，研究了睾丸间质细胞对镉自身耐受性的可能机制，重点是巯基代谢。用低剂量镉（3.0 μmol/kg，皮下注射）对大鼠进行预处理。这种低剂量镉预处理可预防24小时后给予的正常致睾丸病变剂量镉（20.0 μmol/kg，皮下注射）的坏死作用。预处理24小时后，通过胶原酶分散法分离睾丸间质细胞，并与镉（1.0 mM）孵育1小时。与未预处理的对照组相比，单独的体内镉预处理可使全细胞（17%）和胞质溶胶（17%）的GSH水平升高（通过高效液相色谱法测定）。当未预处理大鼠的睾丸间质细胞在体外暴露于镉时，全细胞中的GSH与未预处理对照组相比下降了8%，与体内镉预处理大鼠的细胞相比下降了21%。在从预处理大鼠分离并在体外暴露于镉的睾丸间质细胞中，全细胞中的GSH水平正常，胞质溶胶中的GSH水平略有升高。在整个睾丸中，低剂量镉使胞质溶胶（34%）和细胞核（14%）中的GSH总体水平降低。半胱氨酸水平也有变化，与全睾丸间质细胞和胞质溶胶中GSH的变化相似。通过电泳评估，体内低剂量镉预处理和体外镉暴露均未显著改变低分子量睾丸镉结合蛋白的水平。这些结果表明，巯基代谢，特别是GSH增加，可能是睾丸间质细胞对镉自身耐受性的一个因素。
