116
STRAIN DIFFERENCES IN THE RESPONSE OF THE MOUSE SKELETON
TO EXTERNAL BETA IRRADIATION
D. J. Simmons, R. Hakin,* and Helen Cummins
Irradiation of mice with external Sr®-Y™ applicators provides
a way to control the dose rate and time of exposure of the
skeleton and other tissues to beta ravs. Therefore, toxicity
information may be obtained which is impossible to resolve
by the use of internal emitters. This investigation concerns the
skeletal changes that were produced by preliminary exposures
of three strains of mice to body surface doses of 5000 to 7200
Rads. Several strain differences in response were found.
INTRODUCTION
The results from experiments which have measured
the skeletal response to continuous whole-bedy x or
gamma irradiation (100-200 Rads/day)} or to single
or multiple pulses of x rays (600-8000 Rads) admuinistered over relatively short time periods suggest that
radiation interferes with normal growth processes,
Some of the end points studied have been total bone
length,“-> the state of calcification,'® the histologic
integrity of the cartilage plates,“ 7? the ability of
cells in the cartilage and bone to sustain DNA synthesis,{) the rate of fracture healing,'') and the changes
in bone alkalime phosphatase concentrations, which are
believed to measure (indirectly) the numbers of functional osteoblasts. 17 1) With certain dose schedules,
however, there has been tissue recovery.1)
In an autoradiographic study of the kinetics of a
heterogeneous population of osteogenic cells in the ir-
radiated rat femur (1750 Rads), Kember"® reported
an initial decrease in the numberof cells that could be
flash-labeled with tritiated thymidine curing the first
two davs, but full recovery on the sixteenth day. Recovery did not occur after a dose of 3000 Rads. In continuous irradiation studies (20 days), the reduction in
the thymidine labeling indices became particularly severe as the dose was increased (84, 176, and 415 Rads/
day); the time period of greatest damage occurred
during the initial four days, but thereafter there
evidence that the degree of damage leveled off and
there was at least partial recovery. Adaptation to
tinuous irradiation has been noted for gut“!
marrowcell populations.‘
was
that
conand
Age, species, and the genetics of animals have also
been shownto affect the ability of tissue cells to adapt
to a particular dose level of irradiation, Thus, several
laboratories have demonstrated strain differences in
the normal incidence of bone tumors‘?*: 18) in mice and
rats, and the incidence of bone tumors in mice follow*CSUI Honor Student, Spring, 1967. Present address: Harvard Biological Laboratories, Harvard University, Cambridge,
Mass.
ing the parenteral administration of bone-ser
emitters such ag ®8Sr@? and sr, '?)
This report is a preliminarystudyof the chang
the skeletons of three strains of Argonne Cad7
which had been subjected to partial-body irradi:
from an external °°Sr-®°Ybeta source. This metho:
been employed by Auerbach and his associates‘
study epidermal cell population kinetics in mic
radiated with high doses at a slowrate. Interest
focused upon the histologic changes in the epiph
growth plates and trabeculae in the primary spon
following irradiation and the time required for
skeletal tissues to recover from the insult.
MATERIALS AND METHODS
Animals from three genetic strains of male Co7 .
black (HB = C47 BL/6 ANL [ANL 66]), and ha
white (H), and haired analogues (HW), each
months old were exposed in a total-body surface
irradiator
(9°Sr-°°Y)
designed
by
Auerbach
Brues.{**) The Sr-°°Y source was in the form ©
ramic microspherules embeddedin polyurethane s|
The sheet formed the inner lining of a 4% long a:
numtube placed inside a wooden box, which was =:
by a 4,” thick fixed aluminumshield at one en:
a similar but movable shield at the other. Irradi
was performed byinserting a mouse confined in a
tilated Lusteroid test tube within the source for 1]
16 hr, but the head of the mouse was shielded fro:
radiation by a 1” thiek glass shield. Dosimetric =t:
using solid fluorod dosimeters in Lucite phantons
eated a surface dose rate of 455 Rads/hr whicl
ereased to 68 Rads/hr at a 3-mm depth—well w
the range of the surface tissues of the knee Joint.
total-body surface doses, then, for 11-hr and 16-!
radiation periods were 5000 and 7200 Rads, re
tively. The maximum dose rate delivered to the «
lar elements in the epiphyseal medullary ea
(about 5 mmfrom the surface) might be expeetc
der optimal geometrical conditions to be on the«
of 20-30 Rads/hr. However, it was difficult to e-ti
the actual doses delivered to the knee Joints. We ¢l
know, for instance, 1f the knee joints were in co:
with the walls of the Lusteroid tube during the ¢
11- to 16-hr exposure period. A few control anu
both stressed {restrained in the test tubes) an:
stressed were included in this study, but they we:
sacrificed with the mice killed one day after irr
tion to establish base line values.