Murine strain differences in the volume effect and incidence of radiation-induced colorectal obstruction

Interindividual variation in the level of normal tissue damage after radiotherapy has been clinically observed. Murine models have suggested that there may be a genetic component to the variation in susceptibility of different radiation-induced normal tissue complications. Currently, there are no experimental data available describing interstrain differences in the "volume effect" for irradiated normal tissues, such as the colorectum. The aims of this study are to determine if there are strain differences in: 1. the incidence of colorectal obstruction; and 2. the volume effect, after irradiation of the colorectum using two mouse strains that are known to vary in their susceptibility for developing pulmonary fibrosis.

Various lengths (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 137Cs 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 function of length and dose at 6 months after irradiation. The Threshold Probability model was fit to the length-response data.

C57B1/6 mice developed colorectal obstruction at significantly higher incidence 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 length of colorectum that had to be irradiated before obstructions were observed.

Strain differences in the incidence of radiation-induced 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 different for the two strains is consistent with the concept that there may be a critical threshold amount of colorectal tissue that can tolerate a high dose without complication, and that the dimensions of the threshold may vary among individuals.