Early Recovery for Intestinal Stem Cells, as a Function of Dose per Fraction, Evaluated by Survival Rate after Fractionated Irradiation of the Abdomen of Mice

The additional dose <tex-math>$D_{r}$</tex-math> necessary to reach a given biological effect, when a fraction D_s is split into two equal "subfractions" <tex-math>$2D_{i}$</tex-math> separated by an interval of time i, has been studied as a function of the dose per fraction D_s. LD₅₀ of mice, scored 20-30 days after irradiation on the abdomen, has been chosen as biological endpoint ("intestinal death"). When smaller doses per fraction, D_s and <tex-math>$2D_{i}$</tex-math> were studied, they had to be delivered N times (<tex-math>$N\times D_{s}$</tex-math> or <tex-math>$N\times 2D_{i}$</tex-math>), the number of fractions N being adapted to their size in order to reach a suitable rate of survival. The overall treatment time for each compared protocol was kept constant. Intervals i between the two subfractions <tex-math>$2D_{i}$</tex-math> of 3.5 and 24 hr were studied. No significant difference appeared in the variation of <tex-math>$D_{r}$</tex-math> as a function of D_s related to interval i for the two considered intervals. For i = 3.5 hr, additional dose <tex-math>$D_{r}=2D_{i}-D_{s}$</tex-math> may be ascribed mainly to a difference in cellular repair (Elkind repair) between the compared radiation regimes or, in other words, <tex-math>$D_{r}$</tex-math> may be considered as the "differential recovered dose" related to cellular repair when a fraction D_s is split into two equal subfractions <tex-math>$2D_{i}$</tex-math> separated by an interval i. <tex-math>$D_{r}$</tex-math> was found to be very small for the doses per fraction currently used in radiotherapy (<tex-math>$D_{s}\leq 300\ {\rm rad}$</tex-math>). It increases rather rapidly when D_s exceeds 400 rad and reaches about 300 rad for <tex-math>$D_{s}\cong 1000\ {\rm rad}$</tex-math>. On the other hand, variation of <tex-math>$D_{r}$</tex-math> as a function of D_s was not very different for "intestinal death" and the other "gross" criteria we have investigated: skin reactions on mice, skin reactions on patients, tumor regression on patients. A differential effect related to fraction number is then unlikely between these tissues in the usual conditions of radiotherapy. Finally, in a fractionated radiation treatment, the total dose corresponding to a given effect does not depend very much on the number of fractions, provided that the overall time is kept constant and that the doses per fraction do not exceed 300 rad.