HISTOLOGICAL CHANGES AFTER IRRADIATION 1121 



mitoses becomes very small after 5 or 6 days and many of the dividing 

 cells are degenerate. During the second and third weeks many of the 

 cells seem shrunken. In the succeeding weeks the polymorphism of the 

 cells becomes greater, and many of the cells appear swollen and poorly 

 stained. The epidermis shrinks to two or three layers of cells beneath the 

 cornified layer. If the epidermis is not completely destroyed, a period of 

 mitotic activity may set in (fifth to eighth week). From this time on 

 the epidermis is composed of normal appearing cells. With still larger 

 doses this layer degenerates, and consequently after several weeks the 

 entire epidermis in the irradiated area has been destroyed. This epi- 

 dermal degeneration has been claimed to be the result of destruction of 

 dividing cells. More properly, it is the expression of injury to resting 

 cells which becomes apparent only when the cells divide some time later. 

 After complete degeneration of the epidermis, regeneration is said to 

 occur mainly, if not exclusively, by ingrowth of epithelium from the sur- 

 rounding uninjured epidermis. In laboratory animals exposed to intense 

 or prolonged doses of external (3 rays, regeneration is helped also by 

 proliferation of those hair follicles which are not destroyed by these 

 shallow penetrating rays. The regenerating epidermis is often thin and 

 very susceptible to mechanical and other injuries. This friable epi- 

 dermis may persist for some years. After long-continued irradiation and 

 a long latent period, it has been the source of malignant tumors, particu- 

 larly following the softer X rays used so extensively in the early days of 

 radiology. 



Derma. A dose of 600 to 800 r total-body irradiation in laboratory 

 animals calls forth an exceedingly mild inflammatory reaction character- 

 ized by slight hyperemia, a very low-grade migration of heterophil 

 leukocytes and lymphocytes, some destruction of mast cells, and a barely 

 perceptible edema by 24 hours (Lacassagne and Gricouroff , 1941 ; Schinz 

 and Slotopolsky, 1925; Snider, 1948a). 



In man an erythema due to dilatation of the blood vessels is elicited 

 with 600 to 700 r of hard X rays over relatively small areas. The 

 erythema appears in the first day or so, lasts for a few days, and dis- 

 appears, to reappear on or about the eleventh day. This second ery- 

 thema lasts three or four weeks and gradually merges into a stage of 

 pigmentation of the skin (Ellinger, 1941). 



With larger doses the inflammatory changes are more marked and 

 persist longer. After repeated exposures, giant fibroblasts may be found 

 many months later (Maximow, 1923). Perhaps the most important 

 effects are on the blood vessels, which show marked arteriolar changes. 

 It is claimed that with doses up to 1200 r the vascular changes are reversi- 

 ble, but that with higher doses permanent damage to endothelium and 

 especially to the smooth muscle and elastic fibers results. The swollen 

 or vacuolated endothelial cells may form tufts extending into the lumen. 



