1164 RADIATION BIOLOGY 



LD 50 died of leukemia as compared to per cent of the controls. Expo- 

 sures below that dose have caused only few leukemias thus far (Upton 

 et al., unpublished data). 



While depression of hemopoiesis immediately after exposure to ionizing 

 irradiation is reversible, the liability of late changes of which leukemia is 

 most important appears irreversible. This varies greatly with species, 

 strains of animals, mode and dose of exposure, and is influenced by 

 several factors. In mice the smallest dose of X radiation which depresses 

 lymphopoiesis is about 25 r and the smallest dose which causes leukemia 

 is somewhat below 200 r. Rats are possibly susceptible to the induction 

 of leukemia by radiation (Metcalf and Inda, 1951) ; rabbits and guinea 

 pigs, and probably also dogs, are refractory, but no large-scale studies in 

 which animals were observed during their entire life span have been 

 reported in species other than these. 



The leukemogenic potency of X radiation was first demonstrated 

 experimentally in mice by Krebs et al. (1930). Of 5500 mice exposed to 

 sublethal doses of X radiation 3.5 per thousand developed lymphoid 

 leukemia as compared to 0.6 per thousand of the controls. Furth and 

 Furth (1936) exposed large numbers of mice of three unrelated strains to 

 one or a few doses of 300-400 r of X radiation and found a sevenfold 

 increase in lymphoid leukemia, mainly of mediastinal type, and an eight- 

 fold increase of myeloid leukemia. Subsequent work by several investi- 

 gators disclosed the following: (1) Repeated, well-timed exposures are 

 more leukemogenic than single exposures. (2) The leukemia induction 

 rate is increased with the dose. (3) All strains of mice that were carefully 

 tested proved susceptible although there are marked strain and sex differ- 

 ences in susceptibility. (4) In no species other than the mouse, and 

 possibly the rat, has leukemia been induced experimentally, but adequate 

 follow-up of the exposed animals has been done only in mice, rats, rabbits, 

 and guinea pigs. (5) Gamma radiation of radium and fast and slow neu- 

 trons of the atomic reactor likewise increased the incidence of leukemia 

 in mice. (6) Leukemia induction by radioactive substances other than 

 P 32 has not been reported in animals; it has been described, however, in 

 handlers of radioactive substances. 



In most strains of mice spontaneous leukemias are thymic in origin. 

 Operative removal of this organ (Furth, 1946) or its involution brought 

 about by cortisone (Upton and Furth, unpublished data) diminish the 

 incidence of spontaneous leukemias or their induction by irradiation 

 (Kaplan, 1950b; Kaplan et al., 1951). Hueper (1934) exposed mice bear- 

 ing spontaneous mammary tumors to repeated doses of 30-80 r of X 

 radiation once a week over a period up to six weeks. His treatment 

 caused extensive myeloid hyperplasia with extensive myelopoiesis of the 

 spleen; the greatly increased incidence of leukemia in Hueper's experi- 

 ments suggested that irradiation caused a leukemic transformation 



