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

Abstract

In previous investigations it has been demonstrated that in various animal species increasing doses of x-rays in the form of total body irradiation produce an increasing mortality rate (1, 2). Data concerning the influence of dose fractionation on the lethal effect produced in mice by total body irradiation are presented in this paper. The influence of dose fractionation on the biologic effect of x-rays has been the subject of a large number of investigations. From the accumulated evidence it appears that fractionation usually decreases the effect of a given dose administered in one exposure. In certain tissues and organs with high reproductive capacity, however, as, for example, the testis (3) and malignant tumor tissue (4), the effect of the fractionated dose was found to be more pronounced. The mammalian body is composed of tissues known to react differently to dose fractionation. A study of its influence on the organism as a whole appears, therefore, of special interest. Methods A total of 253 white male mice has been used in these experiments. The radiation factors employed were as follows: 200 kv.p., 10 ma, 0.25 mm. Cu and 1.0 mm. Al inherent filtration, corresponding to a half-value layer of 0.75 mm. Cu. The intensity of the radiation was 23.4 r/min. The distance from the target to the animal container was 50 cm., and the total field size 20 × 20 cm. The set-up for the exposures was the same as in our previous experiments (2). Doses of 1,000, 500, and 400 r/air were given in one exposure and in fractions of 100 r/air on consecutive days (simple dose fractionation). These single exposure doses according to our previous experiences represent the LD 100, 50, and 35, respectively. The choice of 100 r/air as the dose for each fraction of treatment was determined by previous experience, which showed that this dose represents the maximum effective dose, i.e., the dose which in single exposure produces a marked effect within the irradiated body without causing fatalities. Mortality rates for both groups, those receiving the radiation in a single exposure and those receiving the same total dose in equal installments, have been established by recording the number of fatalities daily. A graphic presentation of the results is made, as previously, by using the days after exposure as abscissa values and the percentage mortality as ordinate values. For correct comparison the graphs for the fractionated treated animals have been transformed in such a manner that the zero day in the fractionated group is the day on which the total dose in this group has been accomplished (e.g., zero day for 500 r fractionated is the fourth day after beginning of treatment). Results As shown in Figure 1, fractionation of each of the three investigated doses results in a decrease in the mortality rate. The significance of these observations is illustrated in Figure 2.