PATTERNS OF CELLULAR PROLIFERATION AND AIRWAY BRANCHING IN CULTURED FETAL HAMSTER LUNG EXPLANTS

Lungs were removed from hamsters at gestational day 12 and cultured in BGJb medium under the following conditions: (1) alone, (2) with 5% fe tal bovine serum (FBS), (3) with defined additives (with and without v itamin A), and (4) with defined additives but lacking both epidermal g rowth factor (EGF) and vitamin A. Patterns of cell proliferation were determined by immunochemical labeling for bromodeoxyuridine (BrdU) and airway branching was evaluated in each explant. After 4 days in BGJb alone, an orderly but limited branching pattern occurred, and labeling was greater in the epithelium than in the connective tissue. With FBS a relatively normal branching pattern occurred, and labeling was near ly equivalent in connective tissue and epithelium. With defined additi ves the connective tissue was heavily labeled in the compact region su pporting the distorted bronchioles and in the loose flange at the peri phery; removing only vitamin A did not alter these patterns. Removing both vitamin A and EGF caused an extensive but distorted epithelial br anching pattern that extended to the periphery of the explant (a flang e of loose connective tissue did not form); BrdU labeling was sparse. These results indicate that EGF played a major role in contributing to alterations in the growth and development of fetal hamster lung.