HISTOLOGICAL CHANGES AFTER IRRADIATION 1113 



degeneration in the zone of provisional calcification (Heller, 1948a). 

 This is observed in rats 3 days after a single dose of 600 r of X rays (total- 

 body) and is followed by partial or complete separation of epiphyseal 

 cartilage from the primary spongiosa and eventual recovery with resump- 

 tion of growth (see section on Bone). 



The greater and more sustained damage to cartilage produced by 

 certain internally administered radioactive isotopes parallels their greater 

 injurious effects on bone, and varies with the dosage and with the age of 

 the animal and the consequent stage of growth of its bones. Swelling 

 and death of cells of the epiphyseal cartilage are noted early after deposi- 

 tion of most bone-seeking isotopes. The effects are especially severe in 

 young rats, in which separation of the cartilage from the bone begins at 3 

 days and is nearly complete 7 days after a Sr 89 dose of 2.9 /xc/g (Heller, 

 1948a). By 11 days the entire epiphyseal cartilage is several times the 

 normal width and many cartilage cells are dead, especially in the zone 

 bordering the metaphysis. The articular cartilage cells, particularly 

 those facing the epiphyseal cavity, are either dead or greatly enlarged. 

 In some instances the articular cartilage becomes separated into several 

 portions by connective tissue. By three or five months (depending on 

 the dose and the particular isotope) that portion of the cartilage not 

 destroyed by radiation from the deposited isotope has continued its 

 growth and moved away from the zone of damage; growth in length of 

 the bones continues in histologically normal although slower fashion, and 

 the animals are permanently stunted. 



In rats injected with radium, 0.5 /xc/g, the width of the cartilage plate, 

 at least twice the normal at two months, increases still more at three and 

 five months. At this last interval the cartilage has been invaded by 

 vascular connective tissue, which extends transversely from the region 

 of the periosteum and separates large portions of the hypertrophic 

 cartilage, often 30 cell layers deep, from the rest. 



In mice, in which growth in length of the bone ceases early, Sr 89 also 

 causes an abnormal hypertrophy and vacuolization of cartilage cells at 

 most intervals, but conspicuous from 90 to 197 days after 3.6 juc/g and as 

 late as 70 days after 0.86 /xc/g. The cartilage plate becomes thicker with 

 marked irregularities owing to the increased number of hypertrophic 

 cells. After higher dosages, from 5 to 15 juc/g, the same changes occur, 

 but earlier. The effect of radium is similar but even more severe, despite 

 its doubtful deposition in the epiphyseal cartilage at early intervals and 

 its absence at 40 days. From 8 to 40 days after a radium dose of 1 /xc/g, 

 swollen and degenerating cartilage cells of the epiphyseal cartilage 

 encroach even into the deeper layers of the plate. Eighty days after a 

 dose of 0.5 iic/g, multiplication of the cartilage cells has increased the 

 width of the plate two or three times and dead cartilage cells are numer- 

 ous. The irregularity of this invasion of connective tissue results in 



