Early cytokinetic and morphological response of rat lungs to inhaled benzo(a)pyrene, gallium oxide, and SO2

The purpose of this study was to determine if the early cytokinetic and morphological responses of the lung to inhaled particles and an irritant gas are altered by the presence of a carcinogen. Fischer-344 rats were exposed by nose-only inhalation to a combination of benzo(a)pyrene (B(a)P) (7 mg/m3) adsorbed onto gallium oxide particles (22 mg/m3) and SO2 (5 ppm) or to gallium oxide particles and SO2 alone for 2 h per day for 9 days. Serial sacrifices were performed up to 28 days after the beginning of the exposure. Cell proliferation in the lungs was studied in 1-μm-thick glycol methacrylate autoradiographs of tritiated thymidine-labeled tissues. Cytokinetic and morphological changes in the two groups were similar. However, there were several changes associated only with B(a)P treatment such as increased proliferation in most cell types at 8 or 11 days and foci of large proliferating cuboidal cells in the alveolar region. Cell proliferation in airway and alveolar regions of lungs in both groups increased during exposure and decreased subsequently. Small foci of hyperplastic alveolar cells and hypertrophic terminal bronchiolar cells were present in both groups although they occurred more frequently in the group that received B(a)P. These cytokinetic and morphological changes were interpreted as a repair response of the lungs to a toxic insult. Whether the differences between the two treatments were related to the carcinogenic nature of B(a)P or to the toxic nature of B(a)P will be determined in a long-term study.