Radiation induced renal damage in mice: influence of fraction size.

Two functional assays (urine output and isotope clearance) have been used to assess the response of mouse kidneys to localized irradiation. The influence of the size of each X ray dose has been investigated by using single doses and two to 16 equal fractions. The X ray dose in each treatment ranged from 16 Gy as a single dose to 3.5 Gy (X 16 fractions). Three separate experiments were performed, one with and two without anesthetic for the irradiation. Sequential testing of the mice was used to determine the latent period before radiation damage became manifest. Latency was found to be dose dependent; functional defects appeared earlier after higher doses but there was a minimum period of 14-19 weeks before the onset of damage. The repair capacity of the kidney was assessed by comparing isoeffective doses from the dose-response curves. Within 24 hours a recovered dose of 5 Gy was obtained if 2 doses were used instead of one. The isoeffective dose increased with fractionation and a fraction number exponent of 0.42 was obtained. Analysis of the data using a linear quadratic model yielded a low alpha/beta ratio of 0-3.5 Gy. This is similar to values obtained for other late responding normal tissues and implies that the use of small dose fractions will spare the kidney relative to tumors and acutely reacting normal tissues. In conventional radiotherapy more effective sparing of the kidney should be achieved by using thin shielding with each fraction than by completely shielding the kidney for the latter part of the treatment course.