Download Effect of Mammary Tumor Virus Infection on in Vivo Oxidation of

[CANCER RESEARCH 31, 1955-1961,
December 1971]
Effect of Mammary Tumor Virus Infection on in Vivo Oxidation
of Glucose-l-14C and Glucose-6-14C in C3H Mice1
Hans R. Burki2 and George T. Okita
Northwestern University Medical School, Department of Pharmacology, Chicago, Illinois 60611
SUMMARY
The in vivo oxidation
of glucose-1-14C and glucose-6-14C
was measured in C3H and C3Hf female virgin mice of different
ages. C3H virgins after the age of 4 to 6 months exhibited a
faster rate of glucose-6-14C, but not glucose-1-14C, oxidation
than C3Hf factor-free controls. No difference was observed
between the two strains of mice with respect to the blood
glucose level, but C3H virgins attained lower body weights
than C3Hf controls. These results suggested that the mammary
tumor virus, transmitted in the milk of C3H mice, may induce
in the host alterations in regulatory systems controlling growth
and glucose metabolism. The presence of a transplanted
mammary tumor, which had arisen spontaneously in a C3H
exbreeder female, had no effect on body weight and
glucose-6-'4C
oxidation of C3H virgins but caused an
elevation in glucose-6-14C oxidation and a reduction in body
weight in C3Hf virgin hosts. Thus, the level of glucose-6-14 C
oxidation and the body weight of C3Hf recipients of
mammary tumor transplants were comparable to that of C3H
virgins with or without mammary tumor transplants.
controls. There also appeared to exist a correlation between
the magnitude of the metabolic changes and the extent of
cancerous involvement of the mammary tissue in these mice.
For example, C3H exbreeders with multiple tumors showed
the greatest deviations in in vivo glucose metabolism. These
observations seemed to suggest that the increased mammary
tumor yield observed in MTV-infected animals may be related
to distortions of physiological metabolic control systems in
the host by MTV (10). Thus, further experiments were carried
out to explore the consequences of MTV infection on glucose
metabolism in vivo. The purpose of the present study was
2-fold: (a) to investigate the temporal development of
alterations in glucose metabolism in vivo in C3H virgins. Thus,
the rate of oxidation of glucose-l-I4C and glucose-6-14C was
compared in C3H and C3Hf virgins of different ages; (6) to
determine whether the presence of small foci of tumor tissue
might elicit a host response, hormonal or immunological,
which may lead to alterations in glucose metabolism in vivo.
For this purpose, the degradation of glucose-14C was
measured in mice with transplanted mammary tumors.
MATERIALS AND METHODS
INTRODUCTION
Early studies on the genesis of mammary tumors in C3H
mice led to the concept that 3 factors are essential for the
development of mammary tumors: milk-transmitted MTV,3
Mice. C3H and C3Hf female mice were obtained from The
Jackson Memorial Laboratory, Bar Harbor, Maine, and from
Cumberland View Farm, Clinton, Tenn. In one experiment,
C3H and C3HfB females, generously donated to us by Dr.
Walter Heston, NIH, were used. The animals were kept in our
animal quarters for at least 1 month before use and had access
to water and standard mouse diet of Purina laboratory chow
pellets ad libitum.
Chemicals. D-Glucose-1 -14C(specific activity, 7 mCi/mmole)
inherited mammary tumor susceptibility,
and hormonal
stimulation of the breast tissue (6). More recent studies,
however, indicated that the MTV may not be necessary for
tumorigenesis (8, 11, 12) and that adequate hormonal
stimulation of the mammary glands, in genetically susceptible
mice, may be sufficient for mammary carcinogenesis.
Recently, papers of Batra and Okita (5), Ezz et al. (10), and
Okita et al. (18, 19) described alterations in in vivo oxidation
of specifically labeled glucose-14 C to I4C02 in MTV-infected
C3H mice compared
to factor-free
C3Hf controls.
Precancerous and tumor-bearing C3H females exhibited a
faster rate of glucose-6-14C oxidation and also a lower ratio of
glucose-l-14C to glucose-6-14C degradation than did C3Hf
were diluted with 0.9% NaCl solution under sterile conditions
(Millipore filtration) to a concentration of about 4/jCi/ml.
These sterile solutions were stored in the deep freeze at -10°.
At regular intervals, the glucose-l-14C and glucose-6-'4C
'This investigation was supported by USPHS Research Grant CA
07930 from the National Cancer Institute and NIH Training Grant
GM-00162 from the National Institute of General Medical Sciences.
2Present address: Research Institute, Dr. A. Wander Ltd., P. O. Box
2747, 3001 Bern, Switzerland.
3The abbreviation used is: MTV, mammary tumor virus.
Received January 26, 1971; accepted August 3, 1971.
solutions were checked for purity by paper chromatography
(10).
Blood Glucose. Blood glucose levels were determined with a
Technicon Auto Analyzer by a procedure utilizing the
potassium
ferricyanide-potassium
ferrocyanide
oxidation
reduction reaction as described by Hoffman (13). The change
in color was measured at 420 mß.
was obtained from Nuclear Research Chemicals, Inc.. Orlando,
Fla. D-Glucose-6-14C (specific activity, 27.5 mCi/mmole) was
obtained from Nuclear Chicago, Chicago, 111.
For injection purposes, glucose-1-14C and glucose-6-14C
DECEMBER
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1955
Hans R. Burki
Estimation of Tumor Size. The tumor volumes were
estimated by the formula V= (0.4) ab2, where a equals longest
RESULTS
axis of tumor in millimeters, b equals shortest axis in
millimeters, and V equals volume in cu mm (1). Tumor
volumes calculated with this formula were in close agreement
with those found by immersing the tumors in 0.9% NaCl
solution.
Measurement of Expired C02 and 14CO2. The apparatus
Recovery Patterns of CO2 and 14C02. Chart 1 shows a
sample of C02 and 14C02 recovery patterns from a mouse
given an injection of glucose-6-14C, 0.02 ¿/Ci/gi.p. (injection
used has been described previously (16) and consisted of the
following components: an all-glass mouse chamber and a
freezing trap (C02-acetone mixture) connected in series with a
250-ml ionization chamber (Gary stainless steel spherical
ionization chamber) and a CO2 analyzer (Lira Model 300
infrared analyzer). Outputs from both the ionization chamber
and the C02 analyzer were recorded on a Speedomax
recording instrument (Speedomax G Model S Multiple Point
Recorder) as well as fed into an analog-to-digital converter.
The digital output was recorded on a paper tape punch (Friden
tape punch). The equipment was standardized with gases
containing 0.5 and 1.0% CO2 in air as well as with a gas
containing a known amount of 14C02 in air. The experiments
were performed in air-conditioned laboratories where the
room temperature varied between 22 and 24°.
Mice deprived of food for 8 to 14 hr were given i.p.
injections of 0.02 i/Ci/g glucose-14 C and placed into the
mouse chamber. A continuous flow of air of 250 ml/min was
established through the entire system, and a recording of the
expired CO2 and 14C02 was taken every 20 sec. In most
instances, it was sufficient to measure the recovery of 14C02
at O min). For simplification of the presentation of data in this
chart, the amounts of CO2 and 14C02 excreted were pooled
into 5-min segments. Chart 1 demonstrates that the C02
excretion was high for the first several min after the animal
was treated and placed into the mouse chamber. This initial
peak output of C02 correlated with the exploratory activity
of the animal. Later the rate of the CO2 excretion dropped off
considerably as the animal went to sleep. Occasional physical
activity resulted in increased output of CO2. The recovery of
14CO2 increased rapidly within 25 to 30 min after the
injection of glucose-6-14C to reach a peak after 30 to 40 min.
At times of elevated C02 excretion, the recovery of 14C02
was also increased. However, as expected, the specific activity
curve was not appreciably affected by the physical activity of
the animal. The specific activity curve rose to a maximum
between 25 and 40 min after the injection of glucose-6-14C
and decreased steadily thereafter. The cumulative specific
activity curve, 15 to 20 min after the injection of
glucose-6-14C, entered a near-linear phase. The slope of this
05-
for 40 min. In some experiments, the measurements were
extended to 60 min. The length of the recording is indicated in
the respective tables.
All calculations were performed on an IBM 1800 digital
computer utilizing the data punched on to the paper tape. For
each 20-sec segment, the recovery of 14C02 was determined
(expressed in percentage of the injected dose of glucose-14C),
and the excretion of C02 was measured (mmoles CO2
corrected to 0°and 760 mm Hg). Adding all 180 (= 60 min) or
120 (=40 min) 20-sec segments yielded the cumulative
recovery of 14CO2 and the total excretion of C02 for 60 and
40 min, respectively. Also, for each 20-sec segment, the
specific activity (percentage of injected glucose-14C excreted
as 14C02 per mmole of CO2) was calculated. The slope of the
cumulative specific activity curve of 14C02 was calculated,
with the use of all data points between 20 and 40 min after
injection of glucose-14C, by the method of least squares. This
slope (expressed as percentage of 14C excreted as 14CO2 per
mmole of C02 per hr) represents the average specific activity
of the expired ' 4CO2 and is used in this paper to compare the
metabolic activities of different treatment groups.
As in previous studies (10, 19), glucose-1-14C
glucose-6-14C
were
selected
as substrates
for
and
the
measurements
of in vivo oxidation of glucose. These
compounds
are often used to evaluate
the relative
participation
of the Embden-Meyerhof
pathway and the
pentose cycle in the degradation of glucose (15).
Statistics. Statistical significance was determined by the
Student t test.
1956
20
60
80
100
TIME, MINUTES
KO
160
Chart 1. CO2 and I4CO2 excreted by a C3H mouse, age 40 weeks,
givenan i.p. injection, at O min, of glucose-6-14C, 0.02 /iCi/g.
CANCER RESEARCH VOL. 31
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Glucose Metabolism in C3H Mice
GLUCOSE-I-UC
linear portion proved to be highly reproducible in animals of
the same treatment group and independent of their physical
activity. Therefore, this slope (14C02 in percentage of
injected glucose-14C per mmole of CO2 per hr) was considered
not only an accurate but also a convenient measurement of the
rate of glucose-14 C degradation and is used in this paper to
compare the metabolic activity of different treatment groups.
In Vivo Oxidation of Glucose-14C in C3H and C3Hf Virgins
of Different Ages. The first objective of this study was to
investigate the temporal development
of the metabolic
differences between C3H and C3Hf mice observed by Okita
and coworkers. For this purpose, the rate of oxidation of
glucose-1-14C and glucose-6-14C to 14C02 in vivo was
measured in C3H and C3Hf virgins of different ages. All
animals used for this study were free of mammary tumors. The
results of these experiments are presented in Chart 2 and in
Tables 1 and 2.
Chart 2 shows the specific activity curves and the
cumulative specific activity curves of expired 14C02 of
60-week-old C3H and C3Hf virgins, given i.p. injections of
glucose-l-'4C
or glucose-6-14C, 0.02 ¿iCi/g. It may be
GLUCOSE -6- '*C
15-
observed that there was no difference in the rate of excretion
of 14CO2 in terms of specific activity when glucose-l-14C was
used as substrate. In contrast, the rate of conversion of
glucose-6-14C to 14C02 was increased in C3H virgins
40
O
10
TIME. MINUTES
Chart 2. Specific activity curves and cumulative specific activity
curves of expired "CO2 of C3H (o) and C3Hf (•)virgins, 60 weeks
old, given i.p. injections of glucose-1-1 *C or glucose-6-' 4C. Each point
is the average of 5 to 6 mice.
compared to C3Hf controls, the slope of the cumulative
specific activity curve for C3H virgins being significantly
greater (p < 0.01) than that of C3Hf controls.
Table 1 presents a summary of the results of measurements
of glucose-6-14C oxidation in C3H and C3Hf virgins of
different ages. At the age of 18 weeks, no differences were
apparent between the 2 strains of mice with respect to body
Table 1
In vivo oxidation of glucose-6-'4C in C3H and C3Hf mice of different ages
Mice were given i.p. injections of glucose-6-"C, 0.02 jiCi/g, and the expired '4CO2 was measured as
described in "Materials and Methods." All values are mean ±S.E.
"C
recovered
min(%)36.68
0—60
C02
0—60min
(mmoles)2.70
of cumulative
specific activity curve
(% "CO2/mmole
CO./hr)19.60
miceAge
State of
(g)19.0
wkC3Hf
18
virginsC3H
virginsAge
0.320.2
±
0.6n.s."28.7
±
2.4630.82
±
1.50n.s.24.66
±
0.282.31
±
0.14n.s.2.82
±
0.3320.52
±
1.41n.s.14.25
±
±1.123.6
±0.7p
0.0125.8
<
0.9426.80
±
3.06n.s.21.83
±
0.132.37
±
0.21n.s.2.70
±
0.7017.22
±
0.84p±
0.0513.72
<
1.0825.64
±
0.082.56
±
0.08n.s.3.27
±
0.5416.64
±
0.83p±
0.0211.60
<
wk"C3Hf
40
virginsC3H
virginsAge
wk*C3Hf
46
virginsC3H
virginsAge
0.523.4
±
0.5p ±
0.0130.3
<
2.85n.s.25.51
±
wkC3Hf
60
virginsC3H
0.825.9
±
2.1429.77
±
0.223.05
±
virginsNo.55656556Weight
0.7p ±
2.65n.s.Total
±
0.21n.s.Slope
±
< 0.02Total
0.2515.02
±
0.89p
±
< 0.01
'n.s., not significant.
1Duration of experiments. 40 min.
DECEMBER 1971
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1957
Hans R. Burki
Table 2
In vivo oxidation of glucose-1-"C in C3H and C3Hf mice of different ages
Mice were given i.p. injections of glucose-l-"C, 0.02 ¿iCi/g,and the expired "CO2 was measured as
described in "Materials and Methods." All values are mean ±S.E.
"Crecovered0—60
min(%)45.03
cumulativespecific
of
curve(%
activity
"CO2/mmoleC02/hr)19.15
min(mmoles)3.29
—60
4.1336.02
3=
3.25n.s.34.20
±
0.232.78
±
0.28n.s.3.37
±
miceAge
State of
wkC3Hf
18
virginsC3H
virginsAge
±1.1419.4
0.94n.s."30.2
±
wkC3Hf
60
virginsC3H
±1.1126.6
2.1233.25
±
0.133.02
±
virginsNo.6555Weight(g)20.0
1.07p±
2.47n.s.TotalCO20
±
0.07n.s.Slope
±
< 0.05Total
0.4719.92
±
1.39n.s.15.67
±
0.7815.96
±
0.99n.s.
±
" n.s. not significant.
Table 3
In vivo oxidation of glucose-6-"C in C3H and C3HfB mice" of different ages
Mice were given i.p. injections of glucose-6-"C, 0.02 nC\/g, and the expired "CO2 was measured as
described in "Materials and Methods." All values are mean ±S.E.
"Crecovered0—40
min(%)18.48
cumulativespecific
of
curve(%
activity
min(mmoles)1..82 "CO2/mmoleC02/hr)17.73
0.7226.36
±
3.44p±
0.0520.52
<
0.042.15
±
0.08p
±
0.012.51
<
miceAge
State of
wkC3HfB
15
virginsC3H
virginsAge
0.720.0
±
1.7p ±
0.0529.00
<
wkC3HfB
19
virginsC3H
0.919.25
±
2.0531.47
±
0.092.10
±
virginsNo.6464Weight(g)24.5
0.6p ±
3.18p±
0.05p
±
< 0.01Total
< 0.02TotalCOZ0—40
< 0.01Slope
1.3419.66
±
1.56n.s.613.44
±
0.2320.11
±
0.83p
±
< 0.01
"C3H and C3HfB females obtained from Dr. W. Heston, NIH.
a n.s., not significant.
weight and glucose-6-'4C
oxidation as measured by the slope
of the cumulative specific activity curve. Part of the variations
in total recovery of 14CO2 and in the total amount of C02
excreted is due to differences in random physical activity. At
40, 46, and 60 weeks, however, C3H mice oxidized
glucose-6-14C significantly faster and had lower body weights
than did C3Hf controls.
In Table 2 are summarized the results of measurements of
glucose-1-1 4C degradation in 18- and 60-week-old C3H and
C3Hf virgins. There was again a significant difference in body
weight between the 2 strains at 60 weeks but not at 18 weeks.
Contrary to the findings with glucose-6-14C, no significant
differences were found at either age between C3H and C3Hf
mice with respect to the rate of glucose-1-14C oxidation.
Thus, the ratio glucose-l-"*C/glucose-6-14 C degradation was
0.98 for C3Hf and 0.97 for C3H mice, respectively at 18
weeks. At 60 weeks, these ratios were 1.35 forC3Hfand 1.06
for C3H virgins, respectively.
The measurements of glucose-6-14C degradation and body
weight were repeated with C3H and C3HfB virgin females
from Dr. Heston's laboratory. As indicated in Table 3,
significant differences between the 2 strains of mice with
respect to body weight were already apparent at 15 weeks of
1958
Table 4
Blood glucose levels in blood collected from the tails of C3H and C3Hf
mice, ages 64 to 66 weeks
glucose
(mg/100
ml)104.3
GroupsC3Hf
virgins
C3H virginsNo.11
9Blood
±4.9«
97 . 1 ±2.5
" Mean -HS.E.
age, while a significant difference in glucose-6-'4C
oxidation
between C3H and C3HfB virgins was observed at 19 weeks of
age.
Since it is known that the rate of the in vivo oxidation of
glucose-14 C is in part dependent on the body glucose pool, the
blood glucose level was measured in 64- to 66-week-old C3H
and C3Hf virgins. Table 4 shows that there was no significant
differences between these 2 strains with respect to the blood
glucose level.
In Vivo Oxidation of Glucose-14 C in C3H and C3Hf Virgins
with Transplanted Mammary Tumors. Because C3H mice of
age 5 to 6 months and older (14) develop precancerous
hyperplastic nodules in the mammary tissue which are
CANCER
RESEARCH
VOL. 31
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Glucose Metabolism in C3H Mice
BODY
ü C3Hf
VIRGINS
D
VIRGINS
C3H
TUMOR
WEIGHT
VOLUME
T T
4 I
32
s28
D 1200-
g 24
ÃœJ
>1000-
QC
O 800-
O 16
z
o
m 12
Oi
Chart 3. Body weights and mammary tumor
volumes of C3H and C3Hf virgins. T, recipients of
tumor transplants.
UJ
P
600^
_ 400-
8
E 2003
0
DAYS
35
AFTER
8
TUMOR
In vivo oxidation
35
TRANSPLANTATION
of glucose-6-"C
Table 5
in C3H and C3Hf virgins, age 40 weeks, with transplanted
mammary
tumors
Mice were given i.p. injections of glucose-6-"C, 0.02 ¿iCi/g,and the expired "CO2 was measured as
described in "Materials and Methods." Values are mean ±S.E.
Weight1.2.3.4.GroupsC3Hf
Tumor
volume
mm)28.131
cumulative
specific(g)76*i1.0.16< activity curve
ColminoleC02/hr).2524<22<40<it0.±0.•i0.0.701.320
virginsC3Hf
tumortransplant"C3H
virgins with
22P23P849
±63
0.01".6<.2<±0t00.010.,0l7A61418.P17.P18.Pof
virginsC3H
tumortransplant"No.6656(cu
virgins with
23p ±214
< 0.05'
pSlope
°35 days after tumor transplantation.
"Compared to Group 1.
'Compared to Group 2.
characterized
by a high tumorigenic
potential
(17), size in both strains of mice. These tumor nodules increased
experiments were therefore designed to test the possibility progressively in size in C3H virgins only, however, while their
that the alterations in glucose-6-I4C oxidation and in body growth in C3Hf virgins appeared to be retarded.
Table 5 presents a summary of the results of measurements
weight observed in C3H females compared to factor-free
of in vivo oxidation of glucose-6-14C in C3H and C3Hf virgins
controls could be related to the presence of small foci of
tumor tissue in the mammary gland, eliciting a host response with transplanted mammary tumors, 35 days after the
of hormonal or immunological nature (7). For this purpose, 1 inoculation. In C3H virgins, neither the body weight nor the
rate of glucose-6-14C degradation was altered in the presence
mammary tumor, surgically removed from a C3H exbreeder
where it had arisen spontaneously, was homogenized in 0.9% of the tumor transplant. In C3Hf virgins, on the other hand,
the transplantation of the mammary tumor resulted in a
NaCl solution ( l g tumor tissue per 10 ml 0.9% NaCl solution),
and 0.1 ml of this homogenate was injected s.c. into each of 6 significant reduction in body weight and a significant increase
in glucose-6-14C oxidation compared to C3Hf controls. With
C3Hf and 6 C3H virgins. Six C3Hf and 5 C3H virgin mice of
respect to body weight and glucose-6-14C oxidation, the C3Hf
the same age (35 weeks) were used as untreated controls. Body
weights and glucose-6-14C oxidation were measured 35 days virgins with transplanted tumor tissue exhibited now the
characteristics of C3H mice.
after transplantation of tumor tissue (Chart 3, Table 5).
Chart 3 indicates that the transplantation of the mammary
tumor caused a significant reduction (p<0.01)
in body DISCUSSION
weight in C3Hf but not C3H virgins. It may also be observed
The yields of expired 14C02 from glucose-1-C
and
that until around 8 days after inoculation, the tumor nodules
glucose-6-14C may be used, after making several simplifying
arising from the sites of transplantation were about equal in
DECEMBER 1971
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1959
Hans R. Burki
assumptions, to estimate the relative participation of the
pentose cycle and the glycolysis-Krebs cycle pathway in the
metabolism of glucose (15). In this study, it was found that,
after the mice were about 4 months old, the rate of oxidation
of glucose-6-14C, but not of glucose-1-14C, was increased in
MTV-infected C3H mice when compared to factor-free
controls of the same age. This suggests that there was no
difference between the 2 strains of mice with respect to
metabolism via the pentose cycle, whereas there was an
increased degradation via the glycolysis-Krebs cycle pathway
in C3H mice compared to controls. Similar findings have been
published previously (5, 10, 18, 19). Since it was also noted
that MTV-infected C3H mice attained lower body weights
than did C3Hf controls, it seems likely that the alterations in
glucose-6-14C oxidation in C3H mice when compared to
be to create in the host conditions favorable for tumor growth,
provided that the MTV is introduced into the animal at an
early age (14). Thus it has been shown, with recipients of
transplants of mammary tissue from different strains of mice,
that the susceptibility of tumor development is determined at
the level of the mammary gland tissue (8, 9). The presence of
MTV in the recipients of mammary tissue transplants resulted
in a reduction of the average tumor detection age from 400 to
600 days to 200 to 300 days (8). Thus, one may speculate that
the reduction of the average tumor detection age in
MTV-infected mice may have been related to metabolic
alterations produced in the host by the presence of MTV.
controls were caused by a general alteration in regulatory
systems controlling growth and glucose metabolism. With the
available data, no statement can be made about the nature of
the regulatory systems presumed to be affected, although
there is evidence that in vivo glucose-14C metabolism in C3H
1. Attia, M., and Weiss, D. Immunology of Spontaneous Mammary
Carcinomas in Mice. V. Acquired Tumor Resistance and
Enhancement in Strain A Mice Infected with Mammary Tumor
Virus. Cancer Res., 26: 1787-1800, 1966.
2. Barrett, M. K., and Deringer, M. K. The Effect of Foster Nursing
on the Growth of a Transplantable Tumor. Cancer Res., ¡I:
134-138, 1951.
3. Barrett, M. K., Deringer, M. K., and Dunn, T. B. Influence of the
Mammary Tumor Agent on the Longevity of Hosts Bearing a
Transplanted Tumor. J. Nati. Cancer Inst., 13: 109-119, 1952.
4. Barrett, M. K., and Morgan, W. C. A Maternal Influence on the
Growth Rate of a Transplantable Tumor in Hybrid Mice. J. Nati.
Cancer Inst., JO: 81-88, 1949.
5. Batra, K. V., and Okita, G. T. Effect of Spontaneous Mammary
Carcinogenesis on in Vivo Glucose-U-' *C Incorporation in C3H
Mice. Proc. Soc. Exptl. Biol. Med., 125: 1163-1168, 1967.
6. Bittner, J. J. Genetic Concepts in Mammary Cancer in Mice. Ann.
N. Y. Acad. Sci., 71: 943-975, 1957- 1958.
7. Dezfulian, M., Zee, T., DeOme, K. B., Blair, P. B., and Weiss, D. W.
Role of the Mammary Tumor Virus in the Immunogenicity of
Spontaneous Mammary Carcinomas of BALB/c Mice and in the
Responsiveness of the Hosts. Cancer Res., 28: 1759-1772, 1968.
8. Dux, A., and Muhlbock, O. Susceptibility of Mammary Tissues of
Different Strains of Mice to Tumor Development. J. Nati. Cancer
Inst., 40: 1259-1265, 1968.
9. Dux, A., and Muhlbock, O. Propagation of the Mammary Tumor
Agent (Bittner Virus) in the Absence of Mammary Glands in Mice.
J. Nati. Cancer Inst., 40: 1309-1312, 1968.
mice can be influenced by altering the hormonal status of the
animals (10, 19).
The age at which differences in glucose metabolism and
growth between C3H and C3Hf mice became apparent varied
according to the source of the mice. Enhanced oxidation of
glucose-6-14C and reduction in growth occurred earlier in C3H
mice when these mice were compared with the C3HfB strain
than when compared with C3Hf mice. It seems reasonable to
assume that the differences in metabolic characteristics
between the 2 C3Hf strains may have been caused by
prolonged inbreeding in different institutions with consequent
selection for slightly different genetic traits.
Attempts were made to elucidate possible factors that may
have caused the differences in growth and glucose metabolism
between C3H and C3Hf mice. Since only virgin mice were
used, metabolic alterations resulting from pregnancy and
lactation can be excluded. The age (4 to 6 months) at which
metabolic differences between C3H and C3Hf females became
detectable coincides with the age at which hyperplastic
alveolar nodules develop in the mammary tissue of C3H
females (14). Thus, it appeared likely that alterations in
glucose-14C metabolism and growth in C3H females when
compared to factor-free controls may have been due to a host
response to the presence of the tumor tissue. However, in this
study it was shown that the presence of a transplanted
mammary tumor had no effect on body weight and
glucose-6-14C oxidation of C3H mice. It was therefore
concluded that the presence of a tumor mass per se had no
effect ontheseparameters. C3Hf recipients of mammary tumor
transplants, on the other hand, showed an elevated rate of
glucose-6-14C oxidation and a reduction in body weight. This
appeared to suggest that the transplantation of mammary
tumor tissue resulted in infection of the C3Hf recipients with
MTV and probably other pathogens, thus causing a reduction
in body weight and an alteration in glucose-6-14 C oxidation.
In the present experiments, it was also found that mammary
tumor transplants grew well in C3H recipients but not in C3Hf
mice, a finding that has also been reported by others (2—4,7).
This seemed to suggest that one important role of MTV may
1960
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DECEMBER 1971
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1961
Effect of Mammary Tumor Virus Infection on in Vivo Oxidation
of Glucose-1- 14C and Glucose-6-14C in C3H Mice
Hans R. Burki and George T. Okita
Cancer Res 1971;31:1955-1961.
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