F. A. KALLFELZ, C. L. COMAR, P. H. CRAIG AND A. P. CASARETT 
909 
creased population of lymphocytes and atrophy 
i of lymphoid germinal centers seen in the 70X 
dog killed at this time. Such changes were also 
seen after one year or 2,400 rad but were not 
significantly greater in severity at this time 
than at three months. Similar, though less se- 
vere lesions were seen in the 15X animals. 
The testicular lesion amounted to almost com- 
I plete cessation of spermatogenesis in the 70X 
I animal killed at three months after implanta- 
tion and aspermatogenesis in the 70X dog killed 
after one year. The total dose to the testes 
during three months was 140 rads while after 
one year the total accumulated dose was 570 
rads assuming a dose rate of 65 mrads per 
hour. Such changes would probably be expected 
from such a dose at a daily dose rate of approxi- 
mately 1.5 rads.'* 
i Of great interest is the mast cell tumor found 
in association with the connective tissue capsule 
in the 70X dog killed at one year. This region 
(within 1 cm of the implant surface) received a 
total dose in the neighborhood of 18,000 rad 
during the year of implantation. It is true that 
mast cell tumors occur frequently in dogs, and 
it might be argued that the occurrence of the 
tumor in this animal is fortuitous. However, the 
tumor did show some unusual characteristics, 
specifically: 1) mast cell tumors are rare in the 
Labrador Retriever;^ 2) spontaneous mast cell 
tumors arise almost without exception in the 
dermis, or deep layers of the skin, while the 
tumor in question had no association with the 
skin ; 3) the tumor metastasized and this occurs 
only rarely in cases of spontaneous mast cell 
tumor; and 4) the tumor arose at the site of 
maximum radiation dose. Because of these spe- 
cial features it is felt that this tumor may be an 
example of radiation carcinogenesis; however, 
no definite conclusions can be made on the basis 
11 
of this one case. 
The decreased level of erythropoietic ele- 
I ments and megakaryocytes in the marrow of 
' the lumbar vertebrae immediately adjacent to 
the capsule was associated with a dose of ap- 
proximaitely 170 rads in the 15X dog and 750 
rads in the 70X dog killed after one year. 
Only one other group has conducted studies 
j similar to the one in progress at our 
laboratx>ry.^^ Their results to date aire very 
similar to the results reported here. However, 
they have detected fewer pathological changes 
than seen in the current study. This is probably 
due to the fact that their sources are in the 
probable range of IX to 5X, and pathological 
data are given for animals killed after two 
years. Based on our results, two years may be 
too short a time period for the accumulation of 
sufficient dose for distinct biological effects 
from sources in this dose rate range. 
SUMMARY 
Results obtained to date from this study, 
though preliminary, are encouraging. It should 
be emphasized that all clinical and pathological 
changes seen have been in 15X or 70X animals. 
No functional changes have been discerned in 
IX or 5X animals. It is true that the 15X and 
70X animals have been implanted for a longer 
period of time than any of the other dogs and 
have accumulated a much larger total dose. 
However, clinical changes were seen in the high 
dose rate animals at a much earlier time (3 
months) than in the lower dose animals some of 
which have now been implanted for one and 
one-half years. Because of the relatively low 
dose rate in the IX and 5X animals, long term 
studies, i.e., five to ten years, will probably be 
necessary in order to detect possible subtle 
changes such as life-shortening and shortening 
of incidence times for various tumors.^ 
REFERENCES 
1. Cole, D. W., Mott, W. E., and Sagan, L. A. 
Factors relating to the applications of radioisotopes 
to circulatory support systems. Isotopes and Radia- 
tion Tech. 7:138-145, 1969. 
2. MuLLiNS, L. J., and Leary, J. A. Plutoniuni-238 
for biomedical applications. Nuclear Applications 
6:287-297, 1969. 
3. Cross, F. T., and Sheppard, C. In-phantom dosi- 
metry of Plutonium-238 heat sources in relation to 
circulatory support systems. AEC Research and De- 
velopment Report, BNWL-1489, 1970. 
4. Casarett, A. P. Radiation Biology, Prentice-Hall, 
Englewood Cliffs, N.J., 1968. 
5. Post, John E. Personal Communication. 
