Reproducibility of the lethal effect of total-body irradiation in mice.

Abstract

During the past fifteen years we have been engaged in a systematic investigation of the effects of total-body irradiation, using a variety of small laboratory animals, including goldfish, mice, and guinea-pigs. These studies have demonstrated a positive relationship between increase of the administered x-ray dose and the percentage mortality (1–3). We have also been able to show that the lethal effects of total-body irradiation upon fish or mammals can be used advantageously for the study of numerous problems in medical radiation biology, such as depth dose determination (4), the influence of dose fractionation (5, 6), and the pharmacological analysis of the acute radiation syndrome (7, 8). The use of the lethal effect of total-body irradiation in recent years, in laboratories all over the world, brings to the fore the problem of the reproducibility of this effect. In this paper there will be presented pertinent data on mice, collected during the years 1949–53. Procedures and Methods A total of 586 male white Swiss mice of the Institute stock, weighing 25 ± 3 gm., form the biological material of this study. Of these, 144 received a dose of 400 r/air, 322 a dose of 410 r/air, and 120 a dose of 425 r/air, of x-rays generated at 200 kv and 25 ma, with filtration of 0.25 mm. Cu and 1.0 mm. Al, resulting in h.v.l. of 0.8 mm. Cu. The animals were exposed in groups of 12 under full utilization of back-scatter in a Lucite chamber resting on a Masonite phantom of 10 cm. depth (Fig. 1), as previously described (3, 9). Before going into the details of the study, it appears desirable to outline certain procedural points which we recognized as essential to optimum reproducibility of the lethal effect in total-body irradiation. These are listed in Table I. The importance of line-voltage stability is best illustrated by Figure 2, a tracing of input line voltage showing a surge lasting for about thirty minutes and causing a variation of about 14 per cent. This represents one extreme example of similar observations made during one working day. There exists an approximate second power relation of x-ray intensity to the applied tube potential in the range of interest of our study, as shown in Figure 3. This means that even smaller line-voltage changes, e.g., of the order of 5 per cent, may cause the x-ray output to vary between 42.8 and 47.3 r/min., which approximates a change of about 10 per cent in x-ray dose. To deliver a dose of 400 r at a rate of about 42 r/min. would take 9 minutes 31 seconds, a period shorter than the duration of the observed line-voltage fluctuation. Thus, three consecutively administered doses intended to be 400 r/air may actually amount to 375, 400, and 425 r/air. The influence of these changes on the lethal effect is best illustrated in Figure 4, which shows that the respective mortalities for the fourteenth day after irradiation would be 26, 43, and 69 per cent instead of a constant 43 per cent.3