Acute response of mouse kidney clonogens to fractionated irradiation in situ and then assayed in primary culture

Abstract

Although the difference in sensitivity to the changes in dose fraction size between early-responding and late-responding tissues is well established, the underlying mechanisms in terms of target-cell responses are not yet clearly identified for any tissue. The radiosensitivity of mouse kidney cells after in situ single-dose, 2, 8, and 16 fraction X-irradiations was measured in primary culture using a clonogenic assay. The assay was made 12 h after single doses or 12 h after the last dose of the multifraction regimens. When analysed using the linear-quadratic model, as predicted the individual alpha components for all the different fractionation schedules were not significantly different, and the changes in the beta values were consistent with those expected on the basis of the reciprocal fraction numbers. When all four data sets were integrated to derive a common alpha/beta ratio, the result was 4.4 +/- 1.3 (1SE) Gy, or 2.8 +/- 0.9 Gy (a better fit) if the single-dose data set was excluded. These values fall into the range reported for kidney using assays of tissue function at long times after irradiation. Hence, it has been shown for the first time that the fractionation sensitivity of a late-responding organ is mimicked by that of a clonogenic cell population in that organ. The evidence also suggests that the time available prior to fixation of potentially lethal damage does not influence the low alpha/beta ratio observed for the kidney.