374 D. C. VAN DYKE, P. JANSSEN AND C. A. TOBIAS 



After a dose of 10,000 rad, no microscopic lesion was recognizable dur- 

 ing the first few weeks (none by 37 days) , but eventually (84 days or more) 

 a minimum lesion appeared in the irradiated area. 



At doses above 10,000 rad, a microscopic lesion appeared earlier and at 

 a dose of 20,000 eventually (6 weeks postirradiation) led to complete necro- 

 sis and removal of the irradiated zone with healing of the margins. At 20,000 

 rad, the first recognizable morphologic changes were seen by the 5th day. 



Because doses of irradiation differing by 20 9r can easily be difTerentiated 

 by the fluorescein technique, it was thought that this method might be useful 

 in demonstrating whether such variables as age of animal, size of aperture, 

 or type of particle would affect the result. 



A dose of 10,000 rad appeared to be ideal for demonstrating any differ- 

 ences in effectiveness, because at this dose there is a definite time lag fol- 

 lowed by a plateau in response which clearly differentiates it from the next 

 highest or next lowest dose (12,000 or 8.000 rad). 



The effect of age of the rat on flourescein staining of the irradiated brain 

 was studied using 22-day- and 120-day-old rats, a dose of 10,000 rad, and a 

 postirradiation interval of 7 days (4 rats of each age) . The results in the two 

 groups were identical, 3 rats of each group being classed as l-j- and 1 from 

 each group being classed as 2-|-, a response which could not be expected 

 from a dose effect equivalent to 8,000 or 12,000 rad. Thus, the appearance 

 of the fluorescent lesion is not affected by the age of the animal, within the 

 range studied. 



To determine the effect of size of lesion on flourescein staining of the 

 irradiated rat brain, a study was made 7 days after irradiation with 10,000 

 and 8,000 rad through a 4, 2, or 0.5 mm. slit aperture ( 2 mm used in all 

 other studies). The exact dosimetry for the different apertures was deter- 

 mined in the manner described. When the animals were autopsied, all brains 

 given the larger dose showed a clear band of fluorescence corresponding to 

 the position of the beam, and no brain given the smaller dose showed a 

 lesion. Thus the dose-effect relationship appears to be independent of the 

 size of the irradiated area within the limits studied, i.e., 0.5 to 4 mm. 



Two experiments were done to compare the effectiveness of a given dose 

 of alpha particle irradiation in diflerent species. Rats, rabbits, and monkeys 

 were given a single dose of 11,000 rad and examined at various postirradia- 

 tion intervals. In the first series, the earliest time interval was 48 hours, by 

 which time the monkey brain showed a 4-\- fluorescein staining and begin- 

 ning licjuefaction of the irradiated area. The results from examination of 

 fluorescein staining in the second series, in which the time intervals were 

 shortened to get early observations on monkeys, are compared in Fig. 5. 

 Five monkeys given 3,000 rad and autopsied at 3, 5, 8. 12, and 15 days 

 showed no staining with fluorescein. By comparing the results from Fig. 5 



