Repair of sublethal radiation injury after multiple small doses in mouse kidney: an estimate of flexure dose.

Functional kidney damage in mice was measured after a series of fractionated X-irradiations. Doses per fraction of 0.75-12.5 Gy were given as 2, 5, 10, 30, 40, 60, or 80 equal doses in a total treatment time of 4 weeks. Renal function (measured by clearance of 51CrEDTA or hematocrit levels) deteriorated progressively, in a dose related manner, from 20 to 46 weeks after the start of treatment. The changes in renal function versus time were fitted by a polynomial regression through all data and interpolated values for 51CrEDTA clearance were then calculated at 30 and 40 weeks after treatment. Steep dose response curves were obtained and these were used to calculate isoeffective doses for the different fractionation schedules. There was a marked increase in total isoeffective doses from 2-30 fractions and these data were well described by a linear quadratic (L.Q.) expression for damage with an alpha/beta ratio of 2.3 +/- 0.2 Gy. There was only a slight increase in the total isoeffect dose as the size of the dose per fraction was decreased below 2 Gy and the measured isoeffect doses after 40 to 80 fractions were lower than predicted on the basis of an L.Q. model assuming complete repair between successive irradiations. The flexure dose for mouse kidneys irradiated 3 times per day was, effectively, 1 to 2 Gy and hyperfractionation using lower doses per fraction did not lead to significant, additional repair.