Biosynthesis and degradation of collagen in X-irradiated mouse lung.
Fibrosis, characterized by accumulation of collagen, is a delayed result of radiation injury in many tissues, including lung. To investigate its development, synthesis and degradation of collagen were measured in lungs of mice after X irradiation of the whole thorax. The ratio of type I (coarse fibered) to type III (meshwork) collagen was also determined. Synthesis of procollagen, measured as the activities of prolyl-4-hydroxylase and protein disulfide isomerase in lung tissue, was increased at 2 months after X-ray doses of 5, 7.5, and 9 Gy. Maximal increases were observed 6 to 7 months after doses of 9 Gy and persisted up to 15 months after exposure. Increases after 5 and 7.5 Gy were more gradual, but by 1 year after irradiation they had reached levels similar to those after 9 Gy. X irradiation had no effect on the degradation of collagen as assessed by collagenase activity in lung. The ratio of type I to type III collagen, analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of collagen-derived cyanogen bromide peptides, was the same in irradiated lungs as in age-matched controls. Therefore, increased synthesis of procollagen, rather than decreased degradation of collagen or changes in collagen type, is an important factor in the accumulation of collagen in irradiated lung.
MRC Cyclotron Unit, Hammersmith Hospital, London, United Kingdom.
C M
CM
Walklin
R B
RB
Freedman
M P
MP
Law
D000818:Animals; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D008168:Lung / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D011347:Procollagen / Q000096:biosynthesis; D011658:Pulmonary Fibrosis / Q000209:etiology
D011347:Procollagen; D003094:Collagen