DEVELOPMENT OF FIBROSIS AFTER LUNG IRRADIATION IN RELATION TO INFLAMMATION AND LUNG-FUNCTION IN A MOUSE STRAIN PRONE TO FIBROSIS

The development of lung fibrosis after single-dose thoracic irradiatio n was studied histologically in C57L/J male mice. Lung function was mo nitored using uptake of carbon monoxide. During the latent period (pri or to 15 weeks postirradiation) mice were chosen at random, while duri ng the early phase (15-22 weeks) mice were sacrificed when they develo ped a functional deficit of at least 50%. Excess mice with a deficit o f 50% in the early phase were followed into the late phase and sacrifi ced at 31 or 40 weeks. Two scoring methods were used to quantify lung damage. Fibrotic lesions and foci of inflammation were counted for the latent period, and the proportion of nonfunctional acini was determin ed for the early and late phases. After a dose 1 Gy less than the LD(5 0/180), small regions of mild inflammatory infiltration appeared at 6 weeks, and small, focal fibrotic lesions containing numerous macrophag es appeared at 8 weeks postirradiation. The number of fibrotic lesions increased steadily during the latent period in a manner that is consi stent with conversion of inflammatory lesions to foci of fibrosis. Mic e sacrificed upon developing a 50% functional deficit during the early phase had approximately equal proportions of lung affected by fibrosi s and inflammation. Those mice which developed a similar respiratory d eficit in the early phase and were followed into the late phase usuall y showed little change in lung function. However, when sacrificed at 3 1 weeks they had twice as much fibrosis and very little inflammation, suggesting that the inflammatory lesions had become fibrosed. The aver age number of macrophages per unit area of fibrosis declined during th e latent period and changed little during the early and late phases. L ymphocytes and mast cells were also quantified in fibrosed regions.