INFLUENCE OF FRACTIONATION 399 



is suggested that daily doses, each of which is high enough to reduce 

 survival time, produce death by so-called acute mechanisms. In rats 60 

 r per day (of the gamma or 25 r per day of daily short x-ray exposures) 

 would permit a certain measure of recovery from the acute effects, and 

 death would require a large complement of subacute or chronic radiation 

 damage. In guinea pigs, on the other hand, both 60 and 120 r per day 

 (gamma radiation) would be expected to produce death by acute mecha- 

 nisms, as the guinea pig is more radiosensitive than the rat. 



Although early effects are markedly reduced by fractionation, it is 

 possible to obtain definite effects eventually by continued fractions, each 

 one of which is too low to produce a noticeable effect by itself (30). 

 The influence of dose fractionation on the lethal x-ray effect produced 

 by total-body irradiation in the mouse has been studied by Ellinger (11, 

 12). Simple dose fractionation (daily exposures of 100 r) decreased the 

 mortality rates produced by the same dose when given in one exposure. 

 The influence of fractionation on the lethal effect of x-rays was studied 

 in a different way by Henshaw several years ago (30). In these experi- 

 ments, the fractionated exposures (at different daily levels) were con- 

 tinued until death. From the maximum survival time (36 weeks) in 

 the mice exposed to 5 r per day, to the shortest (20 weeks) in mice 

 receiving 25 r per day, the decrease in survival with increase in amount 

 of the daily exposure approximated a straight line. It was also observed 

 that, although animals receiving the smaller daily exposures lived longer, 

 the total accumulated exposure at the time of death was less than that 

 of the mice exposed to the heavier treatments. Henshaw (30) observed 

 that the overall picture of the radiation effect was one of aging (loss 

 of parenchymatous cells together with poor regenerative ability), and 

 that "if radiation acts to hasten the normal process of aging, normal 

 aging would be expected to exert a relatively greater effect in those ani- 

 mals that lived longest, as was observed." It is concluded by Lorenz 

 et al. (46) from studies of mice that the ovarian-tumor-inducing dose is 

 cumulative and independent of dose level. These authors have also re- 

 ported that death following daily exposures is uniformly caused by ane- 

 mia and thrombocytopenia in guinea pigs, but not in mice or rabbits. 

 It should be borne in mind that in some tissues and organs with high 

 reproductive capacity fractionated exposures are more effective. This 

 is apparently true for the testis (14). Although a single massive ex- 

 posure is more likely to produce an immediate and pronounced depopu- 

 lation of the spermatogenic elements, the mitotically inactive spermato- 

 gonia are more resistant and eventually repopulate the tubules. Con- 

 tinued or fractionated exposures are more likely to result in a gradual 

 but steady depopulation of the tubules with eventual permanent sterility. 



