VOLUME EFFECTS AND EPITHELIAL REGENERATION IN IRRADIATED MOUSE COLORECTUM

The use of three-dimensional treatment planning and volume-reduction t echniques in radiotherapy has prompted the development of a number of mathematical models to describe the effect of changing treatment volum e on the probability of associated complications in normal tissues. Ho wever, limited data are available to test or support these models. One prediction of the Probability model and analogous models, which descr ibe the volume-effect relationship for late end points in tissues with a series-type arrangement of functional subunits, is that there is no threshold volume in the development of the end point. This hypothesis was tested in mouse colorectum, a normal tissue with functional subun its suggested to be arranged in series, using the incidence of obstruc tions due to consequential fibrosis as the end point of damage. Variou s lengths of the colorectum of C3Hf/Kam mice were irradiated with sing le doses of 250 kVp X rays. A threshold length between 10 and 15 mm wa s observed after 32 Gy. The Probability model could not describe the d ata adequately, but a modified version that included a threshold volum e term (the Threshold Probability model) provided an excellent fit. In a separate experiment, epithelial regeneration (migration, extracrypt al proliferation and formation of new crypts) was examined as a possib le mechanism for the threshold length. Reepithelialization was complet e after 32 Gy was delivered to lengths below (5 or 10 mm) but not abov e (20 mm) the threshold for consequential obstruction. Proliferation o f epithelial cells outside the crypt on the mucosal surface (i.e. extr acryptal proliferation) may contribute to the regeneration process. Th e data indicate that regeneration of the epithelium after irradiation results in a threshold length of the colorectum in the development of consequential fibrosis, in contradiction to predictions of the Probabi lity model. (C) 1998 by Radiation Research Society.