New Cell Culture System for Pulmonary Carcinogenesis and Inhalation Toxicology

Relatively little is known about the histogenesis and the underlying mechanisms of lung cancer; in particular about the target cell type(s) of carcinogens (Schüller 1987). The same can be said about the mechanisms of epithelial regeneration in the lung after injury by toxic chemicals. One of the morphologically appreciable responses of the lung to such injury is a hyperplastic growth of bronchiolo-alveolar epithelium. There is speculation that type II pneumocytes or Clara cells may give rise to the hyperplasia. Neuroendocrine (APUD) cells and type I pneumocytes are supposed to be less capable of initiating hyperplasia because of their low activity of cell division, although hyperplasia of the former cell type is experimentally inducible (Schuller et al. 1988). Mutual transformation has even been postulated between type II pneumocytes and Clara cells in certain cases (Schüller 1987). There is another cell type which, occurring in a fetal as well as regenerating adult airway epithelium (McDowell et al. 1984; Emura 1985; Strum et al. 1990), closely resembles the small mucus granule cells (SMGC) postulated to be one of the carcinogen targets in the lung (McDowell and Trump 1983). In our cell culture study (Emura et al. 1990) a large population of cells possessing SMGC characteristics are inducible in vitro from an undifferentiated population of airway epithelial cells.