Müller H L, Taya A, Drosselmeyer E, Hotz G, Pickering S, Ray I L, Seidel A, Thiele H
Kernforschungszentrum Karlsruhe, Institut für Genetik und Toxikologie, F.R.G.
Sci Total Environ. 1989 Jul 15;83(3):239-51. doi: 10.1016/0048-9697(89)90096-x.
The binding of 241Am-hydroxide polymers (as models for readily soluble actinide compounds) to the cell components of rat lung was investigated using differential centrifugation, density gradient centrifugation, gel chromatography, carrier-free electrophoresis and electron microscopic autoradiography (with 241Pu). Irregularly shaped and spherical mixed (U, Pu)O2 particles (as models for insoluble actinide compounds) were administered to rats by inhalation and intratracheal installation and the lung and organ retention was determined. Electron microscopic studies were performed with rat lung and with rat and bovine alveolar macrophages exposed to the actinide compounds in vitro. In the case of the mixed (U, Pu)O2 particles the lung retention was independent of the particle shape and route of administration. Whereas 241Am administered as a hydroxide polymer was transferred rapidly from lung to skeleton and liver, only a few percent of the initial alveolar deposit was found in these organs after mixed oxide inhalation. It is concluded that all types of particles are stored primarily within phagolysosomes of alveolar macrophages. In the case of readily soluble compounds, the actinides are solubilized within these lysosomes and become bound to cytosolic ferritin in the alveolar macrophages. They are then released from the macrophages and probably cross the alveolar membranes as transferrin or as low-molecular-weight forms. Insoluble compounds remain within the lysosomes of alveolar macrophages, but there are indications of chemical damage to the lysosomal membranes, causing the particles to lie free in the cytoplasm.
使用差速离心、密度梯度离心、凝胶色谱、无载体电泳和电子显微镜放射自显影术（使用²⁴¹Pu）研究了²⁴¹Am-氢氧化物聚合物（作为易溶性锕系元素化合物的模型）与大鼠肺细胞成分的结合。通过吸入和气管内注入将不规则形状和球形的混合（U，Pu）O₂颗粒（作为不溶性锕系元素化合物的模型）给予大鼠，并测定肺和器官中的滞留情况。对大鼠肺以及体外暴露于锕系元素化合物的大鼠和牛肺泡巨噬细胞进行了电子显微镜研究。对于混合（U，Pu）O₂颗粒，肺中的滞留情况与颗粒形状和给药途径无关。以氢氧化物聚合物形式给予的²⁴¹Am迅速从肺转移至骨骼和肝脏，而吸入混合氧化物后，在这些器官中仅发现初始肺泡沉积物的百分之几。结论是所有类型的颗粒主要储存在肺泡巨噬细胞的吞噬溶酶体内。对于易溶性化合物，锕系元素在这些溶酶体内溶解，并与肺泡巨噬细胞中的胞质铁蛋白结合。然后它们从巨噬细胞中释放出来，可能以转铁蛋白或低分子量形式穿过肺泡膜。不溶性化合物保留在肺泡巨噬细胞的溶酶体内，但有迹象表明溶酶体膜受到化学损伤，导致颗粒游离于细胞质中。
