Olafson R W
J Biol Chem. 1981 Feb 10;256(3):1263-8.
Quantitative determination of tissue levels of metallothionein was performed using differential pulse polarographic analysis. Cadmium induction of mouse hepatic metallothionein was observed to be linear with respect to dose until a sharp saturation maximum was reached. This metal-stimulated synthesis was completely inhibited by actinomycin D. It was found that a 2- and 7-fold molar excess of copper and zinc, respectively, was necessary to induce hepatic metallothionein synthesis equivalent to a single dose of cadmium. Although liver was the most dynamic tissue in terms of synthetic production, the intestine had the highest basal level. However, induction in the latter tissue was greatly decreased relative to liver or kidney, with no measurable synthesis after a single metal dose. Induction kinetics was similar for all inducing metals with the exception of cadmium-induced hepatic protein, which remained unchanged for 2 weeks and decayed with an apparent t 1/2 of 32 days. Furthermore, with the exception of intravenous zinc dosing, which elicited no hepatic biosynthesis, initial induction kinetics was invariant with administration route. It was observed that chronic subcutaneous administration of sufficient cadmium to saturate hepatic metallothionein synthesis resulted in a coincident onset of toxic symptoms.
采用差分脉冲极谱分析法对金属硫蛋白的组织水平进行定量测定。观察到镉诱导小鼠肝脏金属硫蛋白的剂量呈线性关系，直至达到急剧饱和最大值。这种金属刺激的合成被放线菌素D完全抑制。发现分别需要2倍和7倍摩尔过量的铜和锌才能诱导与单剂量镉相当的肝脏金属硫蛋白合成。尽管就合成产量而言肝脏是最活跃的组织，但肠道的基础水平最高。然而，相对于肝脏或肾脏，后一种组织中的诱导作用大大降低，单次金属剂量后没有可测量的合成。除镉诱导的肝脏蛋白外，所有诱导金属的诱导动力学相似，镉诱导的肝脏蛋白在2周内保持不变，以32天的表观半衰期衰减。此外，除静脉注射锌未引起肝脏生物合成外，初始诱导动力学与给药途径无关。观察到慢性皮下注射足够的镉以使肝脏金属硫蛋白合成饱和会导致同时出现毒性症状。
