Lehman-McKeeman L D, Klaassen C D
Toxicol Appl Pharmacol. 1987 Apr;88(2):195-202. doi: 10.1016/0041-008x(87)90005-6.
In this study, induction of the isoforms of metallothionein (MT) by Cd and Zn was determined with a high-performance liquid chromatography method. Rats were injected (sc) with Cd (1-100 mumol/kg) or Zn (100-10,000 mumol/kg) and concentrations of MT-I and MT-II in liver, kidney, and pancreas were measured 24 hr later. In control rats, only MT-II was detected in liver, whereas both forms were detected in kidney. In liver, Cd treatment increased MTs at all dosages tested such that concentrations of MT-I and MT-II were approximately equal. Zn (100-1000 mumol/kg) increased concentrations of MT-II about three times higher than MT-I, but higher dosages increased both isoforms to similar levels. Time-course experiments indicated that, at all times after Cd administration (30 mumol/kg), concentrations of MT-I and MT-II in liver were similar. However, with Zn treatment (1000 mumol/kg), MT-II levels were three times higher than MT-I at all times after 6 hr. In kidney, no differences in induction of the isoforms was observed following Cd or Zn treatment. In pancreas, Zn (300-10,000 mumol/kg) induced MT-I and MT-II to similar levels. Thus, in liver and kidney, Cd induced MT-I and MT-II similarly over a wide range of dosages. However, Zn treatment preferentially increased hepatic MT-II at low dosages but induced MT-I and MT-II to similar levels at high dosages. In contrast, Zn induced MT-I and MT-II to similar levels in kidney and pancreas.
在本研究中,采用高效液相色谱法测定镉(Cd)和锌(Zn)对金属硫蛋白(MT)同工型的诱导作用。给大鼠皮下注射Cd(1 - 100 μmol/kg)或Zn(100 - 10,000 μmol/kg),24小时后测量肝脏、肾脏和胰腺中MT - I和MT - II的浓度。在对照大鼠中,肝脏中仅检测到MT - II,而肾脏中两种形式均被检测到。在肝脏中,Cd处理在所有测试剂量下均增加了MTs,使得MT - I和MT - II的浓度大致相等。Zn(100 - 1000 μmol/kg)使MT - II的浓度增加至MT - I的约三倍,但更高剂量使两种同工型增加至相似水平。时间进程实验表明,在给予Cd(30 μmol/kg)后的所有时间,肝脏中MT - I和MT - II的浓度相似。然而,用Zn处理(1000 μmol/kg)后,6小时后的所有时间MT - II水平均比MT - I高两倍。在肾脏中,Cd或Zn处理后未观察到同工型诱导的差异。在胰腺中,Zn(300 - 10,000 μmol/kg)诱导MT - I和MT - II至相似水平。因此,在肝脏和肾脏中,Cd在很宽的剂量范围内对MT - I和MT - II的诱导作用相似。然而,Zn处理在低剂量时优先增加肝脏中的MT - II,但在高剂量时诱导MT - I和MT - II至相似水平。相比之下,Zn在肾脏和胰腺中诱导MT - I和MT - II至相似水平。