HISTOLOGICAL AND ULTRASTRUCTURAL ALTERATIONS OF THE BRONCHIOLOALVEOLAR REGION IN THE RAT LUNG AFTER CHRONIC EXPOSURE TO A PYROLIZED PITCH CONDENSATE OR CARBON-BLACK, ALONE OR IN COMBINATION

Morphological alterations in the bronchioloalveolar region of the rat lung were examined after chronic exposure to pyrolized pitch condensate or carbon black, alone or in combination, for 18 h/day, 5 days/wk for 10 mo, followed by a clean air period of up to 20 mo. Morphological studies were performed by light microscopy (LM) and transmission (TEM) and scanning electron microscopy (SEM). The main purpose of the overall study was to examine the ultrastructural features of hyperplastic bronchioloalveolar epithelium with the goal of shedding light on the range of cellular phenotypes involved. By LM on routine paraffin sections, three main types of bronchioloalveolar hyperplasia were recognized: bronchiolar type, alveolar type, and poorly differentiated/undifferentiated type. Further examination of hyperplastic foci by TEM revealed that the cellular components of the bronchiolar type of hyperplasia generally resembled those of normal bronchioles, but when juvenile ciliated cells and/or Clara cells were the main components they were not clearly identifiable by routine histologic examination. In the alveolar type of hyperplasia, three different cellular phenotypes were distinguished by combined LM and TEM: characteristic type II alveolar epithelial cells; cells with one or few large vacuoles which ultra-structurally consisted of lamellated material; and low cuboidal to flattened cells with ultrastructural characteristics intermediate between type I and type II alveolar epithelial cells. The poorly differentiated or undifferentiated type of hyperplasia consisted of cell lacking recognizable mature characteristics by routine LM. By TEM, one or more of the following components were found: undifferentiated cells lacking any characteristics of maturation; cells with intermediate phenotypic characteristics of type II and Clara cells; and low cuboidal to flattened cells with features of early squamous metaplasia. We believe that the undifferentiated cell is a stem cell capable of differentiating toward either bronchiolar or alveolar epithelium. Although three main types of bronchioloalveolar hyperplasia can be recognized, the boundaries between them are blurred. Even at the ultrastructural level, there is a wide range of cellular phenotypes, including apparent intermediate forms. We hypothesize that the phenotypic lability evidenced by the transdifferentiation potential of rat bronchiolar and alveolar epithelium is an important basis for eventual development of tumors in the persistently damaged rat lung.