FIBROBLAST RADIOSENSITIVITY IN-VITRO AND LUNG FIBROSIS IN-VIVO - COMPARISON BETWEEN A FIBROSIS-PRONE AND FIBROSIS-RESISTANT MOUSE STRAIN

Radiation-induced pneumonitis and fibrosis in the lung after treatment to the thoracic cavity for malignant disease currently limit the maxi mum tolerated dose to that region. It has been suggested that heteroge neity in susceptibility to radiation-induced fibrosis exists in the po pulation, implying that the lung tolerance dose is defined by a sensit ive subset of the patient population. Studies of radiotherapy patients have indicated that the survival at 2 Gy (SF2) of cultured skin fibro blasts correlates with the incidence and severity of postirradiation d amage in a number of tissues, suggesting that this assay may be a usef ul predictor of late tissue effects. The goal of the studies presented here was to determine if the radiosensitivity of fibroblasts in vitro isolated from mouse lungs was correlated with the severity of radiati on-induced fibrosis in the lungs of two inbred strains of mice previou sly shown to differ markedly in their susceptibility to radiation-indu ced lung fibrosis: the C3Hf/Kam strain, classified as fibrosis-resista nt, and the C57BL/6J strain, classified as fibrosis-prone. Quantitativ e measurements of lung fibrosis after irradiation were compared to SF2 values for fibroblasts of skin and lung cultured from each strain. Lu ng fibrosis was quantified, using computerized image analysis, as the percentage of fibrosis on Masson's Trichrome-stained lung sections fro m both strains after single doses of radiation to the thorax. For the measurements of SF2, fibroblasts plated at the second passage and grow n to confluence were given single doses of radiation ranging from 0 to 6 Gy. Survival curves were constructed and SF2 values obtained from a linear-quadratic fit to the data. The radiosensitivity of fibroblasts from the lung and skin of SCID mice was determined and served as a po sitive control. The percentage of radiation-induced lung fibrosis was significantly different between the two strains, 5.1% and 0.2% in the C57 strain and C3H strain, respectively. Follow-up of long-term surviv ors (two mice) from the C3H strain did not change this conclusion. How ever, the lung fibroblast SF2 for the C57BL/6J strain (fibrosis-prone) , 0.50 +/- 0.03, was not statistically different from the C3Hf/Kam str ain (fibrosis-resistant), 0.55 +/- 0.07. These data indicate that in v itro radiosensitivity of lung fibroblasts as assayed by survival at 2 Gy does not correlate with the development of lung fibrosis in this mo use model. The SF2 for lung fibroblasts from SCID mice was 0.10. Simil ar SF2 values were obtained for both the C3Hf/Kam mouse lung and skin fibroblasts, 0.55 and 0.56, respectively, and C57BL/6J mouse lung and skin fibroblasts, 0.50 and 0.52, respectively, indicating that the rad iosensitivity of fibroblasts isolated from lung and skin within a stra in is the same. (C) 1996 by Radiation Research Society