title: Cellular aspects of retention and transport of inhaled soluble and insoluble actinide compounds in the rat lung.
abstract: 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.
authors.affiliation: Kernforschungszentrum Karlsruhe, Institut für Genetik und Toxikologie, F.R.G.
authors.forename: H L
authors.initials: HL
authors.lastname: Müller
authors.forename: A
authors.initials: A
authors.lastname: Taya
authors.forename: E
authors.initials: E
authors.lastname: Drosselmeyer
authors.forename: G
authors.initials: G
authors.lastname: Hotz
authors.forename: S
authors.initials: S
authors.lastname: Pickering
authors.forename: I L
authors.initials: IL
authors.lastname: Ray
authors.forename: A
authors.initials: A
authors.lastname: Seidel
authors.forename: H
authors.initials: H
authors.lastname: Thiele
mesh_terms: D008671:Actinoid Series Elements / Q000378:metabolism / Q000493:pharmacokinetics*; D000576:Americium / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D001345:Autoradiography; D003600:Cytosol / Q000378:metabolism; D005260:Female; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D011005:Plutonium / Q000378:metabolism / Q000493:pharmacokinetics*; D011108:Polymers / Q000378:metabolism / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D008671:Actinoid Series Elements; D011108:Polymers; D011005:Plutonium; D000576:Americium