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 condensat e or carbon black, alone or in combination, for 18 h/day, 5 days/wk fo r 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 overa ll study was to examine the ultrastructural features of hyperplastic b ronchioloalveolar epithelium with the goal of shedding light on the ra nge of cellular phenotypes involved. By LM on routine paraffin section s, three main types of bronchioloalveolar hyperplasia were recognized: bronchiolar type, alveolar type, and poorly differentiated/undifferen tiated type. Further examination of hyperplastic foci by TEM revealed that the cellular components of the bronchiolar type of hyperplasia ge nerally resembled those of normal bronchioles, but when juvenile cilia ted cells and/or Clara cells were the main components they were not cl early identifiable by routine histologic examination. In the alveolar type of hyperplasia, three different cellular phenotypes were distingu ished by combined LM and TEM: characteristic type II alveolar epitheli al cells; cells with one or few large vacuoles which ultra-structurall y consisted of lamellated material; and low cuboidal to flattened cell s with ultrastructural characteristics intermediate between type I and type II alveolar epithelial cells. The poorly differentiated or undif ferentiated type of hyperplasia consisted of cell lacking recognizable mature characteristics by routine LM. By TEM, one or more of the foll owing components were found: undifferentiated cells lacking any charac teristics of maturation; cells with intermediate phenotypic characteri stics of type II and Clara cells; and low cuboidal to flattened cells with features of early squamous metaplasia. We believe that the undiff erentiated cell is a stem cell capable of differentiating toward eithe r bronchiolar or alveolar epithelium. Although three main types of bro nchioloalveolar hyperplasia can be recognized, the boundaries between them are blurred. Even at the ultrastructural level, there is a wide r ange of cellular phenotypes, including apparent intermediate forms. We hypothesize that the phenotypic lability evidenced by the transdiffer entiation potential of rat bronchiolar and alveolar epithelium is an i mportant basis for eventual development of tumors in the persistently damaged rat lung.