Lethal Irradiation of Mice with High Doses of Roentgen and Gamma Rays

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Abstract
Roentgen Irradiation Experimental Procedure: White mice of a heterogeneous population obtained by cross-breeding several strains were divided into groups of 10 animals each and were irradiated over a wide dosage range, under identical conditions, with a D.E.W. 215 type tungsten anticathode Siemens tube.2 The factors were as follows: 200 kv., 10 ma., 1.0 mm. Al filtration, maximum output 470 r per minute at 23 cm. Various dosimeters (Hammer, Strauss, Küstner,Victoreen) were tried, but the best results were obtained with small graphite-bakelite ionization chambers (1) put at our disposal by Dr. L. H. Gray,3 which permitted direct determination of the total energy absorbed by the mice (2). Following irradiation, the animals were observed at frequent intervals so as to determine as accurately as possible the survival time. From the individual survival times for each dose, the mean survival time and its standard deviation were calculated by the log-probits graphical statistical method (3), the Bliss group correction (4) being previously made. For lethal irradiation, the mean survival time seems to be a satisfactory measure of radiosensitivity of an animal population, and its variation coefficient gives the amplitude of natural or induced variations of such radiosensitivity (Fig. 1). Experimental Results: The curve reproduced in Figure 2, based on 943 animals, shows the relation of dose to mean survival time. Four areas are apparent: (1) The first deaths followed irradiation with 100 r and the mortality rate increased rapidly with the dose, reaching 100 per cent at 800 to 1,000 r (5). After a period of normal behavior—the so-called latent period—the classical signs of radiation sickness appeared. The coats of the animals became dull and shaggy and they displayed asthenia, diarrhea, nystagmus, kyphosis, emaciation, and dyspnea prior to death. (2) From 800 r to about 13,000 r an interesting phenomenon was observed, expressed on the curve by a plateau. In this dose range the mean survival time remained relatively constant at 80 hours, in spite of variation of dosage in a ratio as high as 1 to 15. This observation may be explainable bythe "impact theory," assuming that death is due to injury of a "target" corresponding to an essential vital mechanism. This target would be a small but highly radiosensitive fraction of the body4, and the ionization produced outside of this "sensitive volume" would be practically ineffective until a dose of 13,000 r was attained. A variation of both the cross section (hit probability) and radiosensitivity (action probability) of this target may account for the individual variations in radioresistance. (3) From 13,000 r the survival time gradually diminishes as the dose increases, and after a shorter latent period the animals show symptoms of a much more acute and rapid poisoning.

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