OXYGEN-INDUCED CHANGES IN PROTEIN-SYNTHESIS AND CELL-PROLIFERATION INCULTURED LUNG SLICES

Elevated fractions of inspired O-2 induce significant remodeling of th e airways and vasculature of the lung. The present study was undertake n to determine the direct effects of altered levels of O-2 on protein synthesis and cell proliferation in lung tissue cultured in vitro. Rat lungs were inflated with low-melt agarose, cut transversely into 1-mm sections, and cultured in a serum-free medium for up to 7 days in the presence of 10, 21, 40, or 70% O-2. Tissue structure integrity was ma intained as assessed by light and electron microscopy. Fractional synt hesis rates (FSR, %protein/day) of soluble protein from cultured lung homogenates demonstrated an O-2 concentration-dependent response. Tiss ue cultured in the presence of 70% O-2 exhibited the highest FSR. The FSR of tissue cultured in 21 or 40% O-2 did not differ and demonstrate d FSR values greater than tissue cultured in 10% O-2. Cell proliferati on was assessed histologically in parenchymal gas-exchange regions of lung slices cultured in the presence of 5-bromo-2'-deoxyuridine. Label ing indexes for tissue cultured in 21, 40, or 70% indicated an O-2-dep endent increase in cell proliferation after 3 days in culture followed by a return to baseline levels after 7 days. Tissue cultured in the p resence of 10% O-2 showed no change in cell proliferation over time. T he data indicate a direct influence of O-2 on lung cell growth and pro liferation. Additionally, these studies show that this in vitro model may be suitable for further understanding of the mechanistic basis inv olved in proliferative events during lung injury.