Further Studies on the Influence of Dose Fractionation on the Lethal X-Ray Effect Produced by Total Body Irradiation in Mice

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Abstract
The influence of dose fractionation upon the lethal effect of total body roentgen irradiation on mice has been previously reported (1). The present paper describes the change in effect of the absolute lethal dose LD100 of x-rays in mice, with fractionation into single doses of various sizes and when different over-all exposure times are employed. Methods A total of 220 white male Swiss mice were used in this experiment. Twenty of these served as unirradiated controls. The irradiation factors employed were as follows: 200 kv.p., 10 ma., 0.25 mm. Cu and 1.0 mm. Al total filtration, corresponding to a half-value layer of 0.75 mm. Cu. The intensity of the radiation was 23.4 r/min. and the target-skin distance was 50 cm. A field 20 × 20 cm. was employed, and the set-up for the exposures was the same as in our previous experiments (2). The doses used were as follows: 1,000 r was given to 63 mice in a single exposure. 1,000 r was given to 40 mice, using 100 r daily on ten consecutive days. 1,000 r was given to 33 mice over a sixteen-day period, with single doses of 100 r. 1,000 r was given to 21 mice over an eighteen-day period, 12 doses of 75 rand 2 doses of 50 r being administered. 1,000 r was given to 41 mice over a twenty-day period, in 50 r doses. The method of recording deaths and the presentation of the results are as previously described. The days after exposure were used as abscissa and the percentage mortality as ordinate values (Fig. 1). For correct comparison, the graphs for the animals treated by fractionation have been transformed in such a manner that the zero day in a fractionated group is the day on which the total dose in that group has been accomplished. Results Our results are summarized in Figure 1. Comparison of curves A and B shows that simple dose fractionation with one-tenth of the lethal dose (B) reduced the mortality rate from 100 per cent to 9C per cent. A slightly greater reduction was obtained in the mortality rate when the same single dose was employed, but the time of exposure was extended from ten to sixteen days (curve C). However, the reduction in mortality rate becomes strikingly pronounced when the single exposures are reduced to 75 r per dose and the time extended to eighteen days. Noteworthy is the fact that further reduction in the single exposure to 50 r and the over-all time to twenty days, produced only an insignificant additional decrease in mortality rate. The general appearance of the animals was in agreement with the decrease in mortality rates, and it was noted that the severe radiation sickness produced with a single exposure of 1,000 r (2) became relatively less manifest as fractionation was increased. In group E, the physical appearance of the mice was almost indistinguishable from that of the controls.
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