Blood, 1957, Vol. 12, No. 3, pp. 251-260.
© 1957 American Society of Hematology, Inc.
The Effect of the Amount of Isologous Bone Marrow Injected on the Recovery of Hematopoietic Organs,
Survival and Body Weight after Lethal
Irradiation Injury in Mice
PAUL URSO 1 and
C. C. CONGDON 1
1 Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee.
Work performed under USAEC Contract No. W-7405-eng-26.
The relation between the amount of isologous bone marrow injected into a
lethally irradiated mouse and its 30 day survival, its bone marrow response, the
histology of the bone marrow in its left femur, its peripheral blood leukocyte
count, the weight of its thymus, spleen, and body, and its appearance showed
that quicker recovery of these end points occurred with increasing amounts of
bone marrow administered.
The bone marrow parameter was the quickest to respond to the varying
amounts of bone marrow injected. In addition, no optimum dose of bone marrow
was found in these experiments for this end point. This indicates that the bone
marrow of an irradiated mouse could be made to show even quicker return to
normal by injection of greater amounts of cells.
The peripheral blood leukocyte count and the spleen weight also showed very
quick recovery with the massive doses of bone marrow injected. For both end
points, however, an optimum response was reached, which in the leukocytes, was
64.4 x 106 -237.9 x 106 cells injected, and in the spleen weight, 12.8 x 106
-237.9 x 106. An optimum response for thymus weight was also found with bone
marrow doses of 64.4 x 106 - 237.9 x 106 cells. The cell dose for the optimum
response in recovery of body weight was 12.8 x 106 - 237.9 x 106.
Optimum 30 day survival was reached with injection of 64.4 x 106 bone marrow cells in these experiments. However, doses from 12.8 x 106 to 64.4 x 106 cells
were not tested. The dose of bone marrow cells that was calculated to give 50 per
cent 30-day survival was 0.42 x 106 (0.17 x 106, 1.92 x 106) cells for the males
and 1.06 x 106 (0.42 x 106, 2.51 x 106) cells for the females. The calculated dose
of bone marrow cells that would give 1 per cent 30-day survival of the males was
0.008 x 106 (0.0008 x 106, 0.0284 x 106) and for the females 0.0102 x 106
(0.001 x 106, 0.040 x 106) cells. These point estimates seem to be unreliable in
view of the extremely large 95% confidence intervals. However, in experiments
done by other workers at the National Cancer Institute similar to those reported
in this paper, M. Schneiderman determined a threshold dose ranging from 0.0026
to 0.0320 x 106 cells by a somewhat different analysis of the data.7 Jacobson et al.
cite a figure of 3-5 x 106 bone marrow cells from young donor mice as causing
53% 28-day survival in CF No. 1 mice exposed to 900 r.2 In using bone marrow
from older mice, they found that 5-9.9 x 106 cells caused 54.9% 28-day survival.
They also estimate that 50,000 cells are necessary to produce significant recovery
of mice after an LD99 exposure. This figure is similar to that determined from the
results of the present experiments.
The results obtained from mice injected intravenously with a massive dose of
bone marrow 3 days after irradiation indicated that the number of cells in the
bone marrow of the right femur can be elevated within a few hours after injection.
However, this could be observed only in an irradiated animal where the number
of cells in the right femoral bone marrow was already low. A similar observation
was made by Graevsky.8 This finding gives further support to the hypothesis
that intravenously injected bone marrow transplants to bone marrow sites in the
irradiated host.9
Submitted on July 9, 1956
Accepted on August 12, 1956
