MURINE STRAIN DIFFERENCES IN THE VOLUME EFFECT AND INCIDENCE OF RADIATION-INDUCED COLORECTAL OBSTRUCTION

Purpose: Interindividual variation in the level of normal tissue damag e after radiotherapy has been clinically observed. Murine models have suggested that there may be a genetic component to the variation in su sceptibility of different radiation-induced normal tissue complication s. Currently, there are no experimental data available describing inte rstrain differences in the ''volume effect'' for irradiated normal tis sues, such as the colorectum, The aims of this study are to determine if there are strain differences in: 1. the incidence of colorectal obs truction; and 2. the volume effect, after irradiation of the colorectu m using two mouse strains that are known to vary in their susceptibili ty for developing pulmonary fibrosis, Methods and Materials: Various l engths (5.2 to 22.9 mm) of the colorectum of male C57B1/6 and C3Hf/Kam mice were irradiated with a single dose (30 Gy) of Cs-137 gamma rays. Also, various doses (20 to 35 Gy) were given to a single length (22.9 mm) of colorectum. The incidence of obstruction was determined as a f unction of length and dose at 6 months after irradiation. The Threshol d Probability model was fit to the length-response data. Results: C57B 1/6 mice developed colorectal obstruction at significantly higher inci dence than C3Hf/Kam mice at all lengths after a single dose of 30 Gy, In addition, the data showed a strain difference in the threshold leng th of colorectum that had to be irradiated before obstructions were ob served. Conclusion: Strain differences in the incidence of radiation-i nduced colorectal obstruction were observed, consistent with previous studies that showed a strain difference in radiation-induced pulmonary fibrosis. The presence of a threshold length of colorectum that was d ifferent for the two strains is consistent with the concept that there may be a critical threshold amount of colorectal tissue that can tole rate a high dose without complication, and that the dimensions of the threshold may vary among individuals. (C) 1998 Elsevier Science Inc.