1100 RADIATION BIOLOGY 



platelets are discussed in Chap. 16 (by Jacobson). In contrast to the 

 radiosensitivity of the free hematopoietic cells is the great resistance of 

 macrophages, reticular cells, and fat cells, none of which show any evi- 

 dence of damage even with 2000 r or more. This is important since the 

 reticular cells are more primitive than the free stem cells and are the 

 most important source of regenerating hematopoietic cells (W. Bloom, 

 1948a). 



First attempts at regeneration of hematopoietic cells, sometimes during 

 the first week after irradiation, are often abortive at the LD 50 level of 

 total-body X irradiation, but full recovery eventually takes place some 

 weeks later. Regenerating erythroblasts often contain highly con- 

 stricted nuclei, and regenerating myelocytes may be greatly enlarged. 

 Regeneration follows a definite pattern: the gelatinous intercellular sub- 

 stance is largely replaced by fat cells and the dilated venous sinuses 

 resume their normal size. A proliferation of stem cells — hemocytoblasts 

 —arising from mitosis of their own cell kind or by transformation of 

 reticular cells (homoplastic or heteroplastic origin) is followed by active 

 erythropoiesis, later by myelocytopoiesis, and finally by the return of 

 young megakaryocytes. After lower doses of X rays, 400 to 100 r, 

 cellular destruction is less extensive and recovery occurs earlier. The 

 effect of 50 r is scarcely perceptible. The morphological and temporal 

 details of regeneration after very high doses of localized radiation have 

 not been worked out. 



X rays affect the bone marrow much less when administered at the 

 rate of 80 r per day for several weeks than when the same quantity of 

 radiation is given in a single dose (M. A. Bloom, 1948). Daily exposure 

 of mice to external y rays reveals no changes in the marrow with 1.1 r 

 for 16 months (Eschenbrenner, 1946; Spargo et at., 1951). An increased 

 gelatinous replacement of the cellular elements of the marrow, particu- 

 larly in the metaphysis, begins at four months after 8.8 r per day and at 

 six months after 4.4 r per day. The number of immature cells of the 

 myelocyte series (particularly hemocytoblasts) increases progressively 

 from 8 to 16 months in the 8.8-r series. These animals also show a 

 progressive increase in connective tissue mast cells in the marrow (Spargo 

 et at., 1951). In guinea pigs 8.8 r per day produces a low-grade anemia 

 with a sudden terminal ending after some months (Lorenz, Heston, 

 Jacobson, et al., 1953). 



A similar pattern of damage and repair results from equivalent doses 

 of X rays, fast neutrons, and slow neutrons (M. A. Bloom, 1948; Lawrence 

 and Tennant, 1937). With all types of radiation, damage to the bone 

 marrow is roughly proportional to the size of the dose. 



All bone-seeking isotopes tend to accumulate at the growing ends of 

 bones and produce earlier and more severe damage in the marrow there 

 than in the center of the shaft. A somewhat similar but less striking 



