Nolan C V, Shaikh Z A
Toxicol Appl Pharmacol. 1986 Sep 15;85(2):135-44. doi: 10.1016/0041-008x(86)90107-9.
The role of metallothionein or metallothionein-like proteins (MT) in genetic resistance to the testicular and hepatic toxicity of cadmium was examined in inbred strains of mice. Mice of two strains resistant (AJ and C3H/HEJ) or susceptible (129J and DBA/2J) to cadmium-induced testicular necrosis were administered sc 30 mumol CdCl2/kg. The uptake of cadmium and the induction of MT in tissues were determined after 6 hr. The results showed that accumulation of cadmium in liver and kidney tissues of the four strains was very similar. MT levels were elevated up to 20-fold in the liver and up to almost 8-fold in the kidney, resulting in cadmium to MT molar ratios of 6.7 to 10.0 in the liver and 1.2 to 1.9 in the kidney. The greatest increase in hepatic MT as well as the cadmium to MT ratio was in the C3H/HEJ strain which is susceptible to cadmium-induced hepatotoxicity. Testicular cadmium levels were significantly elevated in the two susceptible strains. The basal levels of MT-like protein in the testis were generally higher than those in the kidney. Although, only the testis of 129J (susceptible) showed an increase in this protein after 6 hr, both susceptible strains injected with cadmium had significantly higher levels of the protein as compared to the resistant strains. The 30,000-Da cadmium-binding protein in AJ and CD-1 (susceptible) mouse strains was found to cross-react with the anti-MT-serum. Necrotic changes were visible in the testes of the susceptible strains as a result of cadmium administration. Immunohistochemically, there were no significant differences in the localization of MT in the liver, kidney or testis among the four strains. MT or an MT-like protein was concentrated mainly in the interstitial tissue of the mouse testis, but was also detected in the seminiferous tubules. It is concluded that the strain differences in acute toxicity of cadmium are probably not due to low MT concentration in tissues of the susceptible strains.
在近交系小鼠中研究了金属硫蛋白或类金属硫蛋白（MT）在对镉诱导的睾丸和肝脏毒性的遗传抗性中的作用。给对镉诱导的睾丸坏死具有抗性（AJ和C3H/HEJ）或敏感（129J和DBA/2J）的两个品系的小鼠皮下注射30 μmol CdCl₂/kg。6小时后测定组织中镉的摄取和MT的诱导情况。结果表明，四个品系的肝脏和肾脏组织中镉的积累非常相似。肝脏中MT水平升高至20倍，肾脏中升高至近8倍，导致肝脏中镉与MT的摩尔比为6.7至10.0，肾脏中为1.2至1.9。肝脏中MT增加最多以及镉与MT比值最高的是对镉诱导的肝毒性敏感的C3H/HEJ品系。两个敏感品系的睾丸镉水平显著升高。睾丸中类金属硫蛋白的基础水平通常高于肾脏中的水平。虽然，仅129J（敏感）品系的睾丸在6小时后该蛋白有所增加，但与抗性品系相比，注射镉的两个敏感品系该蛋白水平均显著更高。发现AJ和CD-1（敏感）小鼠品系中的30000道尔顿镉结合蛋白与抗MT血清发生交叉反应。由于给予镉，敏感品系的睾丸中可见坏死变化。免疫组织化学显示，四个品系的肝脏、肾脏或睾丸中MT的定位没有显著差异。MT或类MT蛋白主要集中在小鼠睾丸的间质组织中，但在生精小管中也有检测到。结论是，镉急性毒性的品系差异可能不是由于敏感品系组织中MT浓度低所致。
