Target cells for the polychlorinated biphenyl metabolite 4,4'-bis (methylsulfonyl) -2,2',5,5'-tetrachlorobiphenyl in lung and kidney
Brandt, I.; Lund, J.; Bergman, A.; Klasson-Wehler, E.; Poellinger, L.; Gustafsson, J.A.
Drug Metabolism and Disposition the Biological Fate of Chemicals 13(4): 490-496
1985
ISSN/ISBN: 0090-9556 PMID: 2863115 Document Number: 249215
Light microscope autoradiography was used to determine the cellular localization of the polychlorinated biphenyl metabolite 4,4'-bis([14C]methylsulfonyl)-2,2',5-5'-tetrachlorobiphenyl ([3H]TCB) in the lung and kidney of mice and rats. Microautoradiograms prepared from thaw-mounted freeze sections showed that the radioactivity in the lung was localized in the bronchiolar lumen and epithelium. In methacrylate sections (74-82% of radioactivity extracted), a highly selective labeling was registered in the apical cytoplasm of the Clara cells. A pronounced labeling was present also in certain goblet-like cells containing periodic acid-Schiff-positive granules. Gel permeation chromatography and density gradient centrifugation showed that 80-95% of the radioactivity in lung lavage fluid was bound to a specific protein previously characterized in rat and mouse lung cytosol. The protein appeared to be enriched in the lavage fluid, as compared to lung cytosol. [3H]TCB apparently binds to a protein residing in the Clara and goblet-like cells and the labeled TCB-protein complex is subsequently secreted into the airway lumen. As shown by microautoradiography, the radioactivity in the kidney was confined to a restricted portion of the nephron, predominantly to the apical reigon of the proximal tubular cells.