DIFFERENCES IN CORRELATION OF MESSENGER-RNA GENE-EXPRESSION IN MICE SENSITIVE AND RESISTANT TO RADIATION-INDUCED PULMONARY FIBROSIS

Fibrosis, characterized by the accumulation of collagen, is a late res ult of thoracic irradiation. The purpose of this study was to determin e if extracellular matrix protein and transforming growth factor beta mRNA expression are altered late in the course of pulmonary fibrosis a fter irradiation, and then to determine if these changes differ betwee n two strains of mice which vary in their sensitivity to radiation. Ra diation-sensitive (C57BL/6) and radiation-resistant (C3H/HeJ) mice wer e irradiated with a single dose of 5 or 12.5 Gy to the thorax. Total l ung RNA was prepared and immobilized by Northern and slot blotting and hybridized with radiolabeled cDNA probes for collagens I, III and IV, fibronectin, and transforming growth factor beta(1) and beta(3). Auto radiographic data were quantified by video densitometry and results no rmalized to a control probe encoding for glyceraldehyde-3-phosphate de hydrogenase. Alterations in mRNA abundance were observed in the sensit ive mice at all times, while levels in the resistant mice were unaffec ted until 26 weeks after irradiation. The relationship between extrace llular matrix protein per se and increased mRNA abundance suggests tha t late matrix protein accumulation may be a function of gene expressio n. Differences in levels of transforming growth factor beta mRNA may l ead to strain-dependent variation in fibrotic response and may also co ntribute to the radiation-induced component of pulmonary fibrosis. (C) 1995 by Radiation Research Society