Mechanical Assay of Consequential and Primary Late Radiation Effects in Murine Small Intestine: Alpha/Beta Analysis

Abstract

A portion of jejunum in C3H/HeJ mice was irradiated in situ with 250 kV X rays, and the resulting elastic stiffness increase was used as an assay of chronic fibrotic injury. With data from this assay dose-response curves were evaluated with early- and late-appearing chronic intestinal injuries in two experiments. (1) After split-dose treatment with an interfraction interval of 0.0, 0.25, 0.5, 1.0, 2, 4 or 24 h, the asymptotic dose-recovery ratios in assays at 2-3 weeks and at 4 months were statistically similar, R = 1.34 (95% confidence limits: 1.29-1.39) with t1/2 = 0.75 h (0.48-1.17), and R = 1.36 (1.31-1.42) with t1/2 = 0.49 h (0.21-0.86), respectively, although the slopes of the dose-response curves for the early and late assays differed significantly. (2) Mice received 2, 3, 4, 5, 10 or 15 equal X-ray fractions in 5 days with interfraction intervals of at least 5.5-6 h. The data from the dose responses were used in either of two analyses of variance for calculating alpha/beta values. Using slopes in transformed Fe plots, alpha/beta was 8.5 Gy (6.1-12.5) for the assay at 2-3 weeks and 3.6 Gy (2.4-5.4) at 4 months. Using these and other data we argue that assay at the two times measured separate fibrotic responses to injuries to the small intestine, namely, a rapidly appearing consequential late effect that had the same alpha/beta value as for crypt microcolony assays because it was a sequela of acute inflammation after transient loss of mucosal epithelial integrity after crypt sterilization, and a lower-threshold primary or true late effect with a lower alpha/beta value, which progressively masked the consequential injury.