Waalkes M P, Cherian M G, Ward J M, Goyer R A
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, Maryland 21702-1201.
Toxicol Pathol. 1992;20(3 Pt 1):323-6. doi: 10.1177/019262339202000302.
A recent study from our laboratory has shown that cadmium, a toxic heavy metal, is one of the most effective agents known for inducing hepatocytic transdifferentiation of the rat pancreas. With repeated injections of cadmium, the incidence of rats with pancreatic hepatocytic foci can be as high as 93%. Cadmium is also well known as a very potent inducer of metallothionein, a metal-binding protein that appears to be important in the biologic response to several toxic heavy metals in most tissues, including the pancreas. Therefore, the present study sought to determine if metallothionein was associated with cadmium-induced transdifferentiation of pancreatic cells. Expression of metallothionein was studied immunohistochemically by the peroxidase-antiperoxidase method in tissue sections of the pancreas of rats with pancreatic hepatocytes. High levels of metallothionein were localized primarily within the pancreatic hepatocytes. Surrounding normal pancreatic islet and acinar cells were not immunoreactive. Thus, metallothionein is expressed actively in cells transdifferentiated to hepatocytes by cadmium within the pancreas.
我们实验室最近的一项研究表明，镉这种有毒重金属是已知诱导大鼠胰腺肝细胞转分化最有效的因子之一。通过反复注射镉，出现胰腺肝细胞灶的大鼠发生率可高达93%。镉还是一种非常有效的金属硫蛋白诱导剂，金属硫蛋白是一种金属结合蛋白，在包括胰腺在内的大多数组织对几种有毒重金属的生物学反应中似乎很重要。因此，本研究旨在确定金属硫蛋白是否与镉诱导的胰腺细胞转分化有关。采用过氧化物酶-抗过氧化物酶法对有胰腺肝细胞的大鼠胰腺组织切片进行免疫组织化学研究，以检测金属硫蛋白的表达。高水平的金属硫蛋白主要定位于胰腺肝细胞内。周围正常的胰岛和腺泡细胞无免疫反应性。因此，金属硫蛋白在胰腺内被镉转分化为肝细胞的细胞中活跃表达。
