The mammalian lung is composed of over 40 different cell types. The epithelial cell, which lines the upper respiratory passages and the alveoli, is the apparent target of chemical toxins and environmental pollutants. One way in which the lung responds to these insults is by increasing the size and number of cells in the epithelial lining. The type II alveolar pneumocyte is responsible for the production and storage of surfactant. It has been the subject of considerable interest because of its association with surfactant and its response to chemical injury. Lately, this cell has been shown to contain oxidative enzymes responsible for metabolism of foreign substances (xenobiotic metabolism), which may be related to its cell target specificity. Because of the complexity of this organ, isolated whole lung experiments do not significantly contribute to our understanding of the underlying cellular basis for injury. The focus of this proposal is to elucidate the mechanism(s) of pulmonary reaction to a provocative stimulus by isolating and maintaining the epithelial cells in continuous culture. The cells are isolated from rabbit lung during peak proliferation following exposure to N-nitroso-N- methylurethane. These epithelial cells have been shown to resemble those of the fetal lung in late gestation and have displayed normal morphology and contact inhibition in previously established primary explant cultures. The continuous cultures will then be characterized using classical morphological and biochemical techniques. These qualities will also be compared to existing cell lines of epithelial origin. With the knowledge generated from this project, an in vitro model system for assessing pulmonary toxicity will be constructed.
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