Morphogenesis of O,O,S-trimethyl phosphorothioate-induced pulmonary injury in mice.

The purpose of this study was to establish and characterize an experimental model in mice that examined the pulmonary effects of O,O,S-trimethyl phosphorothioate (OOS-TMP), a contaminant present in commercially important organophosphorus insecticides. Characterization of the model will allow the delineation of comparative effects between species and its possible extrapolation to man, and provide an additional experimental animal species satisfactory for mechanistic-oriented studies on OOS-TMP and related compounds. The morphogenesis of pulmonary injury induced by OOS-TMP was studied in mice by light and transmission electron microscopy. Weanling female C57BL/Ka mice received OOS-TMP dissolved in corn oil by intraperitoneal injection and were studied at intervals from 6 to 168 hr after treatment. Morphologic changes were observed in Clara cells only at the initial time period examined. Injury of pulmonary parenchymal cell populations, including the endothelium and type I alveolar epithelium, occurred after morphologic changes indicative of severe cell injury and necrosis in Clara cells. Endothelial cell injury was accompanied by significant increases in wet lung weight and percentage lung water content. Type I alveolar epithelial cell injury and loss resulted in a bare basal lamina, followed by attenuation, hypertrophy, and hyperplasia of type II alveolar epithelial cells. The results of this study document the successful establishment of a mouse experimental model of OOS-TMP-induced pulmonary toxicity. It is concluded that the Clara cell was the initial and most severely affected pulmonary cell population in mice receiving OOS-TMP. The administration of OOS-TMP in mice also results in marked morphologic alterations in the pulmonary parenchyma that were accompanied by significant changes in lung weight and composition.