MORPHOLOGY AND HISTOGENESIS OF SQUAMOUS-CELL METAPLASIA OF THE RAT LUNG AFTER CHRONIC EXPOSURE TO A PYROLIZED PITCH CONDENSATE AND OR CARBON-BLACK, OR TO COMBINATIONS OF PYROLIZED PITCH CONDENSATE, CARBON-BLACK AND IRRITANT GASES

Female Wistar rats were exposed to different concentrations of a pyrol ized pitch condensate and/or carbon black particles and/or a combinati on of irritant gases for 18 hours/day, 5 days/week for 10 months, foll owed by a clean air period of up to 20 months. Bronchiolo-alveolar hyp erplasia and squamous metaplasia were important components of the resu lting lesions. Squamous metaplasia and associated hyperplasia was inve stigated by routine histology, scanning and transmission electron micr oscopy, and by immunohistochemical detection of various cytokeratins ( CKs). Intensely CK positive squamous metaplasia lacking a distinct str atum spinosum was distinguishable from squamous metaplasia with a dist inct stratum spinosum that reacted weakly CK positive or CK negative. The CK positive type was histologically characterized by narrow interc ellular spaces, the weakly CK positive or CK negative type had markedl y enlarged intercellular spaces. Differentiated hyperplastic epitheliu m and the normal lung parenchyma reacted CK negative. In poorly differ entiated hyperplasia of the alveolar type associated with squamous met aplasia scattered cells with characteristics of squamous differentiati on were detected. Ultrastructurally these cells showed increased amoun ts of filament bundles and immunohistochemically a positive reaction w ith the CK antibody. These cells were regarded as precursor stages of squamous metaplasia of the lung periphery in rats.