RADIATION-INDUCED CHANGES IN TRANSFORMING GROWTH-FACTOR-BETA AND COLLAGEN EXPRESSION IN THE MURINE BLADDER WALL AND ITS CORRELATION WITH BLADDER FUNCTION

Late radiation-induced changes in transforming growth factor beta (TGF -beta), collagen I and collagen III content of the bladder wall, as we ll as morphological alterations of the uroepithelium, were analyzed qu antitatively in an immunohistochemical study. An interlaboratory, i.e. interstrain, comparison of two mouse strains (Amsterdam C3H/Hen Af-nu + and Munich C3H Neu) with different dose-effect relationships for lat e bladder damage was made, choosing radiation doses producing equivale nt functional alterations in both strains (ED(80) of 25 Gy and 19 Gy, respectively, 40 weeks after irradiation). In one strain of mouse, cys tometry was also performed in the same animals at different times afte r irradiation. The TGF-beta staining intensity showed a progressive in crease between 90 and 360 days after irradiation. This increase was si milar in both strains of mouse treated with functionally equivalent do ses (ED(80)) and was less pronounced after a lower, ED(40), dose in th e Munich mice. In both strains, there was a radiation-induced increase in both collagen subtypes from 180 days after irradiation with the ED (80). The ratio of collagen type I/III, however, decreased in the Amst erdam mice and increased in the Munich mice. The relative radioresista nce of the Amsterdam mice may therefore be partly due to a greater con tribution of the elastic collagen type III, affording greater bladder compliance after irradiation. The extent of radiation-induced uroepith elial denudations or papillomatous outgrowths, the TGF-beta staining i ntensity and collagen I/III ratio were each correlated to bladder func tion determined by cystometry for the Munich mice. This correlation wa s statistically significant for all three parameters for group mean re sponses and, with the exception of the collagen I/III ratio, also for individual mice. These experiments indicate that chronic radiation-ind uced alterations in TGF-beta expression and connective tissue metaboli sm in the bladder wall are possibly important factors determining redu ced bladder function after irradiation. (C) 1996 by Radiation Research Society