Late Effects of Thermal Neutron Irradiation in Mice"
A. C. UPTON,J. FuRTH,f ANDK. W. CHRISTENBERRY
(Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tenn.)
a facility designed for irradiation of biological material. It con
sisted of a graphite exposure chamber which could be lowered
by means of a motor-driven hoist into the thermal column, as
shown previously (4). The box was large enough to hold simul
taneously only four mice; the animals were exposed within
thin-walled lucite tubes, two at the bottom and two at the top
of the chamber.
Doximelry.—Thermal neutrons were measured by activa
tion of indium foils, as described previously (4). Determina
tions of the cadmium/indium ratio indicated the presence of
negligible fast neutron radiation (4); however, there was con
siderable contamination with high-energy gamma rays (4, 5).
Exposure.—Siblingmale and female RF mice, 6-8 weeks of
TABLE 1
age, were divided into various groups for exposure to thermal
neutrons and to x-rays as shown in Table 1. The highest dose
MICE EXPOSEDTOTHERMALCOLUMN
given (LDso/30 days) required exposure for approximately 80
RADIATIONS
ANDX-RAYS
minutes at the lower position within the graphite chamber (to
a flux of 0.9 X 10"thermal neutrons/cm'/second, with 6.5 r /min
THERMALCOLUMNDOSE
Total
of contaminating gamma rays). Exposures in the reactor were
con-DURATION
matched by doses of x-radiation that caused equal lethality;
80 minutes in the thermal column at the top of the box (3.3 X
orEXPOSUBE(min.)80
10U n/cm* + 416 r of gamma radiation) corresponded to 80
MICEEXPOSED*9612116112812821812518123691941S8447
minutes of 250 kvP x-radiation at 6.4 r/min, or 512 r (LDj/30
/cm*4.3X10»3.3X10U1.1X10«0.8X10U2.7X10"2.1X10"1.4X10»1.0X10"tami-natinggammaray«
(r)520416ISO104SS26]fiISX-iurDOSE(r)5121283210No.
days). The factors of x-radiation were as follows: 250 kvP, 12.5
t80(B)
ma, 3.5 mm. copper 61tration, TSD 93.7 cm., rate 6.4 r/min.
î8020
(T)
Observations.—Afterirradiation the mice were observed for
the remainder of their lives under standard conditions, each
(B)20
cage containing mice from various dose levels. Purina labora
(T)20S
tory chow and drinking water were available ad libitum, sup
(B)5(T)52.
plemented once weekly by chopped lettuce and carrots. Héma
tologie studies, including counts of white blood cells and
reticulocytes, were performed on small numbers of mice during
(B)2.
5
the initial postirradiation period. Periodically, mice were se
(T)2.50Totalthermalneutrona
5
lected at random from the various dose levels and examined
(as unknowns) with the slit lamp for opacities of the lens ; the
severity of the opacities was graded from 0 to + + + + accord
* Approximately one-half males and one-half females.
ing to a predetermined scale (3). Grade I (+) opacities are
t Bottom of box: approximately 0.0 X 10* thermal neutrons/cmVaec,
0.5 r gamma rays/min.
detectable only with the slit lamp, while those designated
ÃŽ
Top of box: approximately 0.7 X 10* thermal neutrons/cm'/aec, 5.2 r
grade II (++) appear as "mild" opacities when viewed with
gamma rays/min.
the ophthalmoscope.
Post mortem examinations were performed on all animals,
mal neutron irradiation in mice (2, 12, 14, 18, 20),
and tissues were examined microscopically as needed to estab
but the late pathological changes resulting from
lish the major anatomical diagnoses. The mice were observed
until natural death or sacrificed in extremis.
exposure to slow neutrons have been analyzed
Neutrons
of thermal energies, produced in
evitably in the vicinity of nuclear reactors and
neutron generators
by moderation
of escaping
fast neutrons in shielding material and in air,
cause ionization on capture within protoplasm;
their biological effects, therefore, are of interest.
With the development of the nuclear reactor, slow
neutrons have become available in the amounts
required for radiobiological
studies. Several re
ports have appeared on the acute effects of ther-
only incompletely
(13).
MATERIALS
AND METHODS
Exposure facility.-—Thermalneutron irradiation was carried
out in the thermal column of the Oak Ridge graphite reactor in
* Work performed under Contract No. W-7405-eng-26 for
the Atomic Energy Commission.
t Present address is Children's Cancer Research Founda
tion, 35 Binney Street, Boston, Mass.
RESULTS
White blood cell and reticulocyte counte.—The
early effects of irradiation on total white blood
cell and reticulocyte levels in the peripheral blood
are shown in Charts 1 and 2, respectively. The
data on animals exposed at both top and bottom
positions of the treatment chamber in the thermal
column have been combined for simplicity" of
analysis
Received for publication June 24, 1954.
in these and subsecjuent
figures. Charts
682
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UPTONet al.—Neutron Irradiation of Mice
1 and 2 show that the depression and recovery
curves of erythro- and leukopoiesis are nearly
identical following 80 minutes' exposure to x-rays
(512 r) and after 80 minutes' exposure in the ther
mal column.
Cataracts.—Opacities of the lens occurred at
all dose levels (Chart 3) ; the latent period varied
inversely, and the rate of progression and final
severity directly, with the dose. Thermal neutron-
683
vival are illustrated in Charts 4 (females) and 5
(males). Longevity was inversely proportional to
the dose; irradiated males tended to survive
slightly longer than irradiated females. There
were no significant differences between x-rays and
pile radiations, matched in terms of acute lethali-
80min
80 (512r)
tr
o
s
24
12
16
AGE(months)
is
20
DAYS AFTER
25
30
IRRADIATION
CHABT1.—Total white blood cell counts of mice exposed
to thermal column radiations and to x-rays.
, 80 min.
neutrons;
,80 min. (Slid r) x-rays.
CHART3.—Averageseverity of opacities of the lens in mice
exposed to thermal column radiations and to x-rays. The mice
were irradiated at 6-8 weeks of age.
, neutrons;
,
x-rays.
100-
S
*»80-
12-
60-
P 404
20
ÃŽNORMAL
:ÃŽAN6E /Vf
12
16
20
24
AGE AT DEATH (months)
5
10
15
20
DAYS AFTER
K
3O
40
50
60
IRRADIATION
CHART2.—Reticulocyte counts of mice exposed to thermal
column radiations and to x-rays.
, 80 min. neutrons;
,80 min. (513 r) x-rays.
gamma radiation was several-fold more damaging
to the lens than x-radiation, in doses of equivalent
acute lethality. Even after 16 r, opacities devel
oped appreciably earlier than the cataractous
changes occurring in aging nonirradiated controls.
Longevity.—The effects of irradiation on sur
28
32
CHART4.—Longevity of female RF mice exposed to ther
mal column radiations and to x-rays. Heavy lines, neutrons;
light lines, x-rays. Solid lines, 80 min.; dashed lines, 20 min.;
dot-dash lines, 5 min.; very heavy line, control.
ty, in shortening the life span. Reduction of sur
vival was due primarily to neoplastic diseases, of
which leukemia was most important.
Leukemia.—The incidence of leukemia of vari
ous types in relation to time postirradiation is
shown in Charts 6 (female) and 7 (male). Myeloid
leukemias occurred infrequently and late in life
in mice of the RF strain. Their frequency was in-
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Cancer Research
684
creased after 128 r or more of x-radiation and after
comparable doses of pile radiations, the incidence
being greater among males. The peak incidence
occurred at 12-16 months of age. The myeloid
leukemias of irradiated mice were not different,
clinically or morphologically, from those of nonirradiated controls. Great enlargement of the
spleen, moderate enlargement of the liver, and
slight enlargement of the lymph nodes, often with
greenish discoloration (chloroleukemia), were the
usual findings. The degree of maturation of the
myeloid series varied, the predominant cell being
usually the myelocyte or promyelocyte. Myeloblasts were few. Maturation was slight. Necrosis
of the bone marrow occurred in over 50 per cent
100-
80-
60
g
i «M
20-
12
16
20
24
AGE AT DEATH (months)
28
32
CHABT5.—Longevity of male KF mice exposed to thermal
column radiations and to x-rays. Heavy lines, neutrons; light
lines, x-rays; solid lines, 80 min.; dashed lines, 20 min.; dotdash lines, 5 min.; very heavy line, control.
of mice with myeloid leukemia. This lesion, dis
cussed earlier (22), was not observed in other
animals.
Lymphoid tumors of the thymus were increased
equally by near-lethal doses of x-radiation (512 r)
and by corresponding doses of pile radiations
(Charts 6 and 7). These doses hastened their on
set, the peak incidence occurring within the first
year after irradiation. Thymic lymphomas were
more common in females. They were either local
ized in the mediastinum, causing death by com
pression or invasion of adjacent structures, often
with massive hemorrhage, or were accompanied
by generalized lymphomatosis. In contrast to
myeloid leukemias, the generalized lymphomas
were associated with great enlargement of the
lymph nodes and infiltrations in the kidney and
other nonhemopoietic organs. Microscopic ex
amination revealed that infiltrations in the same
organs were common in lymphomas which, on
gross inspection, appeared localized to the medias
tinum.
The frequency of nonthymic lymphomas was
inversely proportional to that of thymic lymphoid tumors. Irradiation had no significant effect
on the incidence of monocytic and reticulum-cell
tumors.
Ovary.—Neoplasms of the ovary occurred con
sistently in mice surviving longer than 18 months
after 128 or 512 r and were rare in controls (Chart
8). X-rays and pile radiations appeared equally
effective in ovarian tumorigenesis at the higher
dose levels; however, although only 32 r of x-radia
tion was definitely carcinogenic to the ovary, the
matching dose of pile radiations failed to increase
significantly the incidence of ovarian tumors. The
neoplasms of the ovary were of varied histological
types, including granulosa-cell tumors, luteomas,
tubular adenomas, hemangiomas, stromal-cell
tumors, cystadenomas, and undifferentiated neo
plasms. Mixtures of distinct histologie types were
common. Métastaseswere very rare. Degenera
tion and necrosis of neoplastic tissue occurred
frequently. Occasionally, uterine hyperplasia in
a tumor-bearing mouse indicated excessive secre
tion of estrogen or progesterone.
Lung.—Tumors of the lung, for the most part
pulmonary adenomas, occurred in 21-25 per cent
of nonirradiated controls. They tended to develop
late in life (Chart 9). The incidence of these neo
plasms was increased but slightly by irradiation
in females and slightly if at all in males. Multicentric growth of pulmonary adenomas was com
mon, and on microscopic examination neoplastic
tissue was frequently observed growing into bron
chi; however, metastasis to pleura or to distant
organs was rare.
Hepatoma.—Tumors of the liver occurred in
approximately 6 per cent of nonirradiated males
and 0.5 per cent of nonirradiated females (Table
2). Their incidence was increased slightly in fe
males by high doses but not in males. Nearly all
observed hepatomas were benign and were not
associated with cirrhosis.
Other neoplasms.—Thesewere encountered spo
radically at all dose levels and comprised a wide
range of cell types (Table 3). There is no conclu
sive evidence that irradiation significantly af
fected their incidence, with few exceptions. Neo
plasms of the Harderian gland were observed in
four irradiated mice, which resembled the tumors
(adenomas and adenocarcinomas) induced in
larger numbers of LAFi mice irradiated by nu
clear detonation (9).
Only one pituitary tumor was found in this
series, but the cranial cavity was examined only
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1954 American Association for Cancer Research.
IO
14
18
22
26
H
LYMPHOID, NONTHYMIC
30
LYMPHOID, THYMIC
filïïl MYELOID
CD
IO
14
18
22
26
MONOCYTIC
30
AGE AT DEATH (months)
CHABT6.—Cumulative incidence of leukemia, per histologie type, in female RF mice exposed to thermal column radiations
and to x-rays.
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XRAYS
80 min (512 r)
IO
14
18
22
26
•
LYMPHOID, NONTHYMIC
MS
MYELOIO
CD
MÃ’NOCYTIC
30
LYMPHOID, THYMIC
10
14
18
22
26
30
AGE AT DEATH (months)
CBABT7.—Cumulative incidence of leukemia, per histologie type, in male RF mice exposed to thermal column radiations and
to x-rays.
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UPTONet al.—Neutron Irradiation of Mice
infrequently, and neoplasms may have been in
duced by irradiation as described previously (9).
Adrenal tumors (adenomas) occurred in five fe
male and six male irradiated mice but in none of
the controls. This suggests that such tumors also
might have been caused by irradiation.
601
O 50-j
30
or
O
S 20-
687
half of the biological effect of thermal column radi
ations, the remainder resulting from contaminat
ing gamma rays, as will be described. Physical
measurements of neutron flux and of gamma radi
ation (Table 1), respectively, were carried out in
the exposure facility, as indicated (4, 5), both
with mice present in and absent from the exposure
chamber. On insertion of mice into a field of ther
mal neutrons, the dosimetry is complicated by a
local reduction in the flux of thermal neutrons and
increase in gamma radiation, as described by
Brennan et al. (2). Thus, a compact group of mice
acting as a neutron "sink" may reduce the total
incident neutron flux as much as 20 per cent, and
the capture gamma rays emitted from the mice
may add considerably to the inherent gamma radi
ation of the thermal column (2).
TABLE2
INCIDENCEOFHEPATOMA
IN MICE EXPOSED
TOTHERMALNEUTRONS
ANDTOX-RAYS
1i I0"
o
8
12
16
20
24
AGE ATDEATH (months)
28
32
CHART8.—Cumulative incidence of ovarian tumors in fe
male RF mice exposed to thermal column radiations and to
x-rays. Heavy lines, neutrons; light lines, x-rays; solid lines,
80 min.; dashed lines, 20 min.; dot-dash lines, 5 min.; very
heavy line, control.
70-
30
10
16
20
24
AGE AT DEATH (months)
CHART9.—Combined cumulative incidence of pulmonary
tumors in female mice exposed to thermal column radiations
and to x-rays. Solid lines, 80 min.; dashed lines, 20 min.; dotdash lines, 5 min.; very heavy line, control.
Mortality rates.—Death rates of mice dying
without leukemia or other neoplastic diseases,
summarized in Chart 10, indicate that longevity
was reduced in proportion to the dose even in the
absence of neoplasia.
DISCUSSION
Physical considerations.—Thermal neutrons
were estimated to account for approximately one-
DURATION
OF
EXPOSURE
(min.)
80
20
5
2.5
0
FEMALES
Thermal
X-ray
column
(per cent)
5.7
4
3
0
0
0
4
0
0.5
MALES
Thermal
column
X-ray
(per cent)
S.I
99
5.5
3.3
7.2
.'i.6
0
6.6
6.1
Conversion of the integral dose of neutrons per
square centimeter to rep entails estimation of the
energy absorbed within the irradiated tissue. The
interaction of impinging thermal neutrons with
the atoms of protoplasm has been analyzed the
oretically (15, 23), and a formula has been de
rived to enable calculation of the energy liber
ated by neutron capture (4). The principal re
actions occurring in mammalian tissue are (a)
hydrogen capture, with emission of a 2.2-Mev
gamma ray, (6) nitrogen capture, with emission
of a 0.62-Mev proton, and (c) boron capture, with
emission of a 2.35-Mev alpha particle (1). The
dose in rep/unit flux of thermal neutrons was cal
culated by Brennan et cd. (2) and correlates favora
bly with recent theoretical (17) and experimental
(16) studies of the absorption of thermal neutrons
in protoplasm.1 Harris, in a more recent analysis
of the Los Alamos data (11), reported that 1.35 X
IO10thermal neutrons per cm2 was equivalent to
1.0 rem of 250-kvP x-radiation for the LDw/30
1A few attempts were made in this study to measure the
absorption of slow neutrons in the mouse by exposing indium
foils in the subhepatic region of the abdomen; this location was
approximately at the center of the mouse, 0.4-0.7 cm. beneath
the abdominal wall. Foils at this site were activated to 75-80
per cent of those exposed on the abdominal skin.
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688
Cancer Research
days of mice, the RBE being 1.5. From this it may
be inferred that 2.0 X 10'°thermal neutrons/cm2
were estimated
to deliver 1 rep of whole-body
radiation. To estimate the RBE, it is necessary
to calculate the rem/rep ratio. In this experiment,
ministered
simultaneously
are apparently
addi
tive (19), the rem contribution
of the thermal
neutrons was calculated by subtracting
the rem
dose of the gamma-ray component from the total
rem dose of combined pile radiations. The doses
TABLE 3
INCIDENCEANDTYPESOFMISCELLANEOUS
NEOPLASMS
OFMICE EXPOSEDTO
THERMALCOLUMNRADIATIONSANDX-RAYS
SEX
Duration of exposure (min.)
Dose* (r)
No. exposed*
80
512
185
20
128
ÕSS
Females
5
32
218
Malen
2.5
16
128
0
0
197
80
512
193
20
128
241
5
32
274
2.5
16
192
0
0
250
No. of mice with tumor
Site
neoplasm:AdrenalAnusBladderBoneBreastHarderian
of primary
2
glandHemangioma
sites)IntestineKidneyPituitarySkinConnective
(various
(sarcoma)StomachTestisUterus
tissue
(endometrium)21113211122
* In this analysis data of x-radiated and pile-exposed mice have been combined.
100-
80-
6CH
P 40-
20-
10
14
18
22
26
3O
AGE AT DEATH ( months)
CHART10.—Combined longevity in female and male RF
mice dying without detectable leukemia or neoplastic diseases
after exposure to thermal column radiations and to x-rays.
Heavy lines, neutrons; light lines, x-rays; solid lines, 80 min.;
dashed lines, 20 min.; dot-dash lines, 5 min.; very heavy line,
control.
as in the Los Alamos studies, 250-kvP x-rays
served as the rem standard. Thus, irradiation for
80 minutes in the pile was found to be equivalent
in terms of acute mortality to 512 r of 250-kvP
x-radiation, or to 512 rem. Because the biological
effects of thermal neutrons and gamma rays ad-
of gamma radiation were converted from r units
to rem by assuming the RBE to be 0.53 on the
basis of the analogous gamma radiations of the
Los Alamos thermal column, compared to 250kvP x-rays (2). The similarity of the energies of
the gamma rays of the two reactors is indicated
by their absorption curves in lead (2, 5) and their
common mode of origin. For the LDw/30 days,
therefore, 3.3 X IO12 thermal neutrons/cm2
(165
rep)2 + 416 r (200 rem) of gamma radiation were
approximately
equivalent
to 512 r of 250-kvP
x-rays; 165 rep of thermal neutrons was thus
equivalent to 512-220 rem, or 292 rem. Since the
RBE is equal to the ratio of rem/rep (2), the RBE
of thermal neutrons for LD6o/30 days is 292/165,
or 1.77. This value is in close agreement with that
found by Harris (11); however, it must be con
sidered only a rough approximation,
since almost
one-half of the biologic effect of the thermal col
umn radiations is attributed
to gamma rays, the
RBE of which is uncertain.
Biological considerations.—Pile radiations and
x-rays appeared not only qualitatively
identical
in their effects on mice, but, matched in terms of
acute lethality, they appeared biologically equiva
lent at each dose level for most late pathologic
12.0 X 1010thermal neutrons/cm»1 rep (11).
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1954 American Association for Cancer Research.
UPTONet al.—Neutron Irradiation of Mice
changes, as well as for early hématologieeffects.
From this it would appear that the RBE of pile
radiations was relatively constant for most of the
parameters in question. A notable exception, how
ever, was cataract. The data of this study do not
enable precise estimation of the RBE for opacification of the lens; however, comparison of the
severity of lesions in pile-exposed and x-radiated
mice (Chart 3) suggests that the RBE for lens
damage is several times higher than that for lethal
ity. The RBE of 14.8 initially reported by Storer
et al. (20) was later estimated to be approximately
7.7 judged on the basis of lens damage present 1
year after irradiation and after recalculation of the
energy deposited within the mouse lens by ther
mal neutron irradiation (11). The latter value
would appear to be consistent with the results of
this study.
Previous reports have stressed the high radiosensitivity of the lens of the mouse (21), which
appears to be a peculiarity of the species (10).
Although detectable opacities resulted from doses
as low as 16 r, such lesions appeared relatively late
and failed to advance markedly even in old age.
Only moderate cataracts resulted from 128 r,
severe cataracts (H—|—(-)only from doses in the
neighborhood of the LDw, and complete opacities
H—I—I—h)were observed only in mice irradi
ated by neutrons at the LDso level. The induction
time of opacities was inversely proportional to the
dose.
Another significant departure of the RBE of
thermal neutrons from that characteristic for
most effects was noted in ovarian tumor induc
tion. Whereas 32 r of x-radiation was clearly car
cinogenic to the ovary (Chart 8), the correspond
ing thermal column exposure was slightly if at
all tumorigenic to the ovary. This is in contrast
to the close agreement between the incidences of
ovarian neoplasms produced by higher doses of
x-rays and pile radiations, respectively. It is pos
sible that 32 r of x-radiation is close to the thresh
old dose for ovarian tumor induction and that the
"matching" dose of thermal column exposure is
probably only slightly beneath this threshold.
Microscopic observations of ova and follicles in
ovaries at this dose level were consistent with the
observed absence of ovarian tumors. The discrep
ancy in the RBE may reflect a relatively high
absorption of thermal neutrons in tissues super
ficial to the ovary. Histologically, the ovarian
neoplasms encountered in this study were similar
to those described earlier in irradiated mice of the
same strain (1). The pathogenesis of these tumors
has been discussed elsewhere (8).
689
Induction of thymic lymphoid tumors by ir
radiation was also anticipated from previous stud
ies (8). The higher incidence of this form of leu
kemia in females is characteristic for most strains
of mice studied thus far and may be due to the
leukemogenic action of estrogen (8). These data
suggest that the threshold dose for thymic lymphoma induction is between 128 r and 512 r; other
studies indicate that it is in the neighborhood of
300 r if given as a single dose (8). The incidence
of nonthymic lymphoid tumors was not markedly
affected by irradiation, as has been observed with
other strains of mice (9).
The greatly increased frequency of myeloid
leukemia in mice of the RF strain exposed to ir
radiation at the 128-r level confirms earlier obser
vations (6). Thus, this strain of mice, being more
susceptible to induction, by irradiation, of mye
loid than lymphoid leukemia, resembles man
more closely than other strains of mice studied
(8). These findings indicate the importance of
genetic factors in the mechanism of neoplasia
induction (8). The higher frequency of myeloid
leukemia after 128 r, compared to 512 r, is attribut
able to the greater longevity of mice at the lower
dose level, since the peak incidence of myeloid
leukemia occurred at 12-16 months of age; at the
512-r level, heavy mortality in the first year of
life from radiation-induced
lymphomas killed
many potentially myeloid leukemic animals. Like
wise, the lower frequency of myeloid leukemia in
the female may have resulted from the greater
incidence of early thymic lymphomas in this sex.
It appears highly significant that the RBE of pile
radiations for both myeloid and lymphoid leukemias was essentially identical with that for
acute lethality.
The slightly increased incidence of pulmonary
tumors in irradiated females (Chart 9) confirms
earlier findings. It is significant that a slight ef
fect appears even after ^ of the LDw If corrected
for reduced longevity, the incidence of tumors was
markedly elevated after high doses of radiation,
an effect somewhat obscured by the long latency
of pulmonary neoplasms; thus, tumors occurred
in 22 of 66 females (33 per cent) surviving 18
months after 80 minutes' exposure, while only 19
of 127 nonirradiated females (15 per cent) had
lung tumors after 18 months of age.
The frequency of hepatomas was only slightly
increased after whole-body irradiation (Table 2),
as noted by Lorenz (7). This is in contrast to the
regenerative hyperplasia and hepatoma forma
tion which often follow larger doses of irradiation
delivered to the liver by intravenously injected
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Cancer Research
colloidal Au198which is selectively taken up in
this organ.3
The observed shortening of the life span by
irradiation in the absence of specific lethal neoplastic diseases (Chart 10) supports the idea that
irradiation accelerates the aging process. This is
also suggested by the hastening of the onset of
neoplasms and by the exaggeration of a non-neoplastic, degenerative change, such as cataract,
which is a characteristic senile alteration. Aside
from neoplasia, the irradiated mice of this study
manifested no specific lesions to which death could
be attributed. They differed in this respect from
mice of another strain in which heavy total-body
irradiation often led to fatal nephrosclerosis (9).
4. CONGER,A. D., and GILES,N. H. The Cytogenetic Effect
of Slow Neutrons. Genetics, 36:397-419, 1950.
5. DARDEN,E. B.; SHEPPARD,C. W.; and EMERSON,L. C.
Gamma-Ray Contamination in the Thermal Neutron Ex
posure Facility of the Oak Ridge Reactor. USAEC Un
classified Report ORNL-100S, 1951.*
6. FURTH, J., and FURTH, O. B. Neoplastic Diseases Pro
duced in Mice by General Irradiation with X-Rays. I. In
cidence and Types of Neoplasms. Am. J. Cancer, 28:54-65,
1936.
7. FURTH, J., and LORENZ,E. Carcinogenesis by Ionizing
Radiations. In A. HOLLAENDEH
(ed.), Radiation Biology.
New York: McGraw-Hill Book Co., 1954.
8. FURTH, J., and UPTON,A. C. Vertebrate Radiobiology:
Histopathology and Carcinogenesis. Ann. Rev. Nuclear
Sc., 3:303-38, 1953.
9. FURTH,J.; UPTON,A. C.; CHRISTENBERRT,
K. W.; BENE
DICT,W. H.; and MOSHMAN,J. Late Effects in Mice of
Ionizing Radiation from an Experimental Nuclear Detona
tion in Mice. Radiobiology (in press).
SUMMARY
10. HAM, W. T., JR. Radiation Cataract. Arch. Ophth., 50:
618-13, 1953.
1. Pathologic effects caused in mice by irradia
tion in the thermal column (thermal neutrons and 11. HARRIS,P. S. Measurement of Slow Neutrons and Co
existing Radiations. Radiation Research, 1:34-42, 1954.
gamma rays) were qualitatively indistinguishable
12. HARRIS,P. S., and BRENNAN,J. T. The Biological Effec
from those of x-radiation.
tiveness of Thermal Neutrons Determined by the De
2. The relative biological effectiveness of ther
crease in Weight of the Spleen and Thymus of the Mouse.
USAEC Unclassified Report LA-1410, 1952.<
mal neutron radiation was essentially the same
for most late effects, such as induction of leukemia 13. HENSHAW,P. S.; SNIDER,R. S.; RILET, E. F.; STAPLETON,
G. E.; and ZIRKLE,R. E. Delayed Effects of Single Doses
and other neoplasms and reduction of longevity,
of Slow Neutrons on Mice. USAEC Declassified Report
as for acute lethality and acute hématologiein
MonH-117, 1946.4
jury.
14.
. Effects of Periodic Doses of Slow Neutrons on
Mice. Ibid., MDDC-754, 1946.«
3. The relative biological effectiveness of ther
15. MITCHELL,J. S. Provisional Calculation of the Tolerance
mal neutrons was several times higher for cataract
Flux of Thermal Neutrons. Brit. J. Radiol., 20:79-82,
induction than for acute lethality.
1947.
4. The RF mouse, like man, is susceptible to 16. SMITH,B. S., and TAIT, J. H. Thermal Neutron Distribu
induction of myeloid leukemia by relatively low
tion in a Slab of Paraffin. Nature, 165:196 1950.
17. SNTDER,W. S. Calculations for Maximum Permissible
doses of ionizing radiation.
Exposure to Thermal Neutrons. Nucleonics, 6 (2) : 46-50,
1950.
ACKNOWLEDGMENTS
18. STORER,J. B. The Biological Effectiveness of Thermal
The authors wish to thank G. E. Stapleton for guidance and
Neutrons in Inhibiting Mitosis in Mice. USAEC Unclassi
assistance in the use of the thermal column of the reactor;
fied Report LA-1400, 1952.«
C. W. Sheppard, A. D. Conger, and E. B. Darden for dosi
19. STORER,J. B., and HARRIS,P. S. Additivity of Thermal
metrie data; and F. F. Farbstein, W. D. Gude, J. J. Lane,
Neutrons and X-Rays in their Acute Lethal Action on
E. S. Ledford, and J. R. Thomson for technical assistance.
Mice. USAEC Unclassified Report LA-1502, 1952.<
20.
. Incidence of Lens Opacities in Mice Exposed to
X-Rays and Thermal Neutrons. Ibid., LA-1455, 1952.4
REFERENCES
K. W.; and FUBTH,J.
1. BALI, T., and FURTH, J. Morphological and Biological 21. UPTON,A. C.; CHHISTENBERRY,
Comparison of Local and Systemic Exposures in Produc
Characteristics of X-Ray Induced Transplantable Ovarian
tion of Radiation Cataract. Arch. Ophth., 49:164-67,1953.
Tumors. Cancer Research, 9:449-72, 1949.
22.
UPTON,A.
C., and FUHTH,J. The Effects of Cortisone on
2. BRENNAN,J. T.; HARRIS,P. S.; CARTER,R. E.; and LANGthe Development of Spontaneous Leukemia in Mice and
HAM,W. H. The Biological Effectiveness of Thermal Neu
on its Induction by Irradiation. Blood (in press).
trons on Mice. USAEC Unclassified Repoit LA-1408,1952,
23. ZIRKLE,R. E. Components of the Acute Lethal Action of
and Nucleonics, 12 (2): 48-57; (4): 31-35, 1954.
Slow Neutrons. Radiology, 49:271-73, 1947.
3. CHRISTENBERRT,
K. W., and FUBTH,J. Induction of Cata
racts in Mice by Slow Neutrons and X-rays. Proc. Soc.
4Information on availability of government reports may be
Exper. Biol. & Med., 77:559-60, 1954.
had from Office of Technical Services, Department of Com
1A. C. Upton and J. Furth, unpublished observations.
merce, Washington 25, D.C.
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1954 American Association for Cancer Research.
Late Effects of Thermal Neutron Irradiation in Mice
A. C. Upton, J. Furth and K. W. Christenberry
Cancer Res 1954;14:682-690.
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