Purine Metabolism in Mouse Ascites Tumor Cells
I. Effect of Preformed Purines on in Vitro
Incorporation of Glycine-2-CU!
ANNAMARIAWILLIAMSANDG. A. LEPAGE
(McArdle Memorial Laboratory, Medical School, University of Wisconsin, Madison 6, Wis.)
In view of the potential importance of purine amounts of inosine (and deoxyinosine) and hypo
xanthine. The pools of inosine and hypoxanthine
antagonists as chemotherapeutic agents, an un
derstanding of the relationship of exogenous seemed to act as traps for the radioactivity from
purines to purine metabolism in normal and neo- glycine-2-C14. D-AMP1 which was not a diluent,
plastic cells is desirable. Edmonds and LePage (2) was not converted by these cells to significant
studied the purine metabolism of Ehrlich ascites quantities of inosine and hypoxanthine. However,
tumor cells in vitro by two technics: the ability of the conversion of AMP to the latter two com
exogenous purine derivatives to dilute incorpora
pounds did not fully account for its effectiveness
tion of glycine-2-C14 into nucleic acids and soluble as a diluent, and the uptake of AMP into nucleic
nucleotides, and the incorporation of C14-labeled acid adenine did not appear to involve a pre
nucleotides and nucleosides. The work reported
liminary conversion to inosine. Thus, a second
was concerned with derivatives of adenine and mechanism for the incorporation of AMP into
hypoxanthine. We have extended the investiga
nucleic acid adenine was probably also involved
tion to derivatives of guanine and xanthine and in the effect of AMP as a diluent of glycine in
have used four ascites-cell tumors. This paper will corporation.
report the studies on incorporation of glycine-2-C14
The extension of these experiments to other
ascites-cell tumors and to additional purine com
into cell purines (de novo synthesis).
Earlier work has shown that the incorporation
pounds has shown that some exogenous purine
of glycine, by de novo purine synthesis, into RNA1 derivatives act to increase the glycine-2-C14 radio
and DNA purines of mouse ascites cells could be activity reaching nucleic acids and that the effect
markedly reduced by the addition of exogenous of some of these compounds differs from one tumor
purines and their nucleoside and nucleotide deriva
to another.
tives (4). To relate these "dilution" effects to path
MATERIALS AND METHODS
ways of de novo purine synthesis, Edmonds and
Ascites cells.—Ascitescells were grown in mice by methods
LePage studied the metabolic fate of the exoge
previously described (4). The Ehrlich and Sarcoma 180 cells
nous purine compounds concurrently with their were carried in female white Swiss mice; the 6C3HED, in fe
effects on the incorporation of glycine-2-C14 in male C3H mice; and the TAS, in male CAFl mice.
Incubation of cells in vitro.—Cellswere centrifuged, washed
Ehrlich ascites cells. AMP, adenosine, and deoxy8 times with isotonic saline (10-15 ml. 0.9 per cent NaCl/ml.
adenosine, which diluted the incorporation, were packed cells) and added to 60-ml. Warburg respirometer ves
converted by the Ehrlich cells to relatively large sels containing 12 ml. of Robinson's medium (5), supplemented
* This research was supported in part by American Cancer
Society Institutional Grant (INSTR-71D), in part by United
States Public Health Service Grant No. C2491, and in part
by the Alexander and Margaret Stewart Fund.
'Abbreviations
used: RNA, ribonucleic acid; DNA,
deoxyribonucleic acid; AS, acid-soluble; AMP, adenosine-5'monophosphate; D-AMP, deoxyadenosine monophosphate;
ADP, adenosine-5'-diphosphate; ATP, adenosine-5'-triphosphate; GMP, guanosine-5'-monophosphate; D-GMP, deoxyguanosine monophosphate; XMP, xanthosine-5'-monophosphate; IMP, inosine-5'-monophosphate; PCA, perchloric acid.
Received for publication November 18, 1957.
with glucose and sodium bicarbonate, and 2.0 junólesglycine2-C14.2Duplicate or triplicate flasks, each containing 80-35 mg.
dry weight of cells, were used for each test and were incubated
in a 95 per cent nitrogen: 5 per cent carbon dioxide atmosphere
at 88°C. Specific activity values from replicate flasks varied
by not more than 10 per cent from the mean. The incubation
was stopped, at 60 minutes unless otherwise indicated, by
tipping 1 ml. of 2.6 M PCA into the flask from the sideann of
each vessel. Supernates from replicate flasks were combined to
provide sufficient acid-soluble components for analysis. In
1Glycine-2-C14 was obtained from Tracerlab Inc. on allo
cation by the U.S. Atomic Energy Commission (approximately
1.1 millicuries/millimole).
548
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WILLIAMSANDLEPAGE—PurineMetabolism in Ascites Tumor Cells. I
experiments in which RNA and DNA were separated, acidinsolubJe residues from replicate flasks were also combined.
The residues were washed 2 times with cold 0.2 M PCA, and
the original supernate plus washings was neutralized with
KOH in the cold. Precipitated potassium perchlorate was re
moved by centrifugation. The supernatant fluid, which is the
extract of cells plus incubation medium, is designated as the
acid-soluble extract.
Isolation of compounds for radioactivity measurements.—
Purines from total nucleic acids, or from RNA and DNA, were
isolated, purified, and measured for radioactivity3 as de
scribed by Edmonds and LePage (2). The system used by these
workers for fractionating the acid-soluble extracts on Dowex1-formate columns, by manual addition of a series of eluants
of increasing formate ¡onconcentration, was modified to give
a better separation of degradation products from guanine
compounds. The modified method is shown in Chart 1. Com
pounds in the various fractions were separated by paper
chromatography as described by Edmonds and LePage (2).
The initial effluent plus water washes from the Dowex-1-for
mate column was further fractionated by chromatography on
a Dowex-50 column and eluted with HC1, before paper chro
matography. Isolated acid-soluble compounds were plated on
aluminum planchéisfor measurement of radioactivity.
RESULTS AND DISCUSSION
Experiments with Ehrlich osciles cells.—Insome
initial experiments with Ehrlich cells, GMP,
guanosine, and deoxyguanosine diluted the 60minute incorporation of glycine-2-C14 into total
nucleic acids, whereas D-GMP did not, in agree
ment with the results (2) for the corresponding
adenine compounds. One, 2, and 4 /¿molesGMP
per reaction vessel diluted glycine incorporation
to the same degree, also in agreement with results
for AMP. An unlabeled pool of 2 /¿molesglycine
had no effect on the 60-minute incorporation of
either AMP-C14 or GMP-C14 (Table 1).
Survey of four ascites-cell tumors.—Table 2 sum
marizes the effects of various preformed purine
compounds on incorporation of glycine-2-C14 into
four ascites-cell tumors. Each result represents the
specific activity obtained when the unlabeled pu
rine compound was added divided by the specific
activity with glycine-2-C14 alone. Duplicate flasks
were averaged for each specific activity value, and
the same cell suspension was used to test all com
pounds in one of the two groups, adenine series or
guanine series. This permitted a comparison of the
magnitude of dilution by related compounds,
since some variation in degree of effect is found
with cell suspensions prepared from different
transplants of a particular ascites tumor. How
ever, the characteristic effect of some compounds
on glycine incorporation and certain differences
between tumors were reproducible and can be
pointed out in the data of Table 2: (a) Dilution
effects were greatest with Sarcoma 180; every
549
compound tested except xanthine was a good dilu
ent of glycine incorporation. (6) Dilution of in
corporation into nucleic acid adenine by guanine
compounds and into nucleic acid guanine by ade
nine compounds differed among the tumors, being
especially high with Sarcoma 180 and low with
6C3HED. (c) Hypoxanthine and inosine were
good diluents of glycine-2-C14 incorporation into
both nucleic acid adenine and nucleic acid guanine
0.20
ZO
TUBE
*-H,0-*OSM-»-OM*-2.0H—
Z
-,
FA
pa
»3.0»H|-4.0M-«4.0M-«4.0*
¡OM
. ¡FA-»«
p*
PA
FA+
+0.4M
FA -f
+0.4M
02MAF
AF
I.OMAF
CHART1.—Typical chromatogram of compounds with ul
traviolet absorption (at 260 m/i) found in acid-soluble ex
tracts from 60 to 70 mg. dry weight of Ehrlich carcinoma cells
incubated in 24 ml. of medium. Solid areas represent com
ponents after incubation with 4.0 jumólesglycine-2-C14; areas
outlined by broken lines, after incubation with 2.0 /tmoles
various purine compounds. The extracts were chromatographed on Dowex-1-formate columns, 1 X 10 cm.
TABLE 1
EFFECTOFGLYCINE
ONINCORPORATION
OFAMP-C14
ANDGMP-C14
INTOEHRLICH
CELLS
SPECIFICACTIVITY
op
NUCLEIC
Adenine
ADDITIONS
ACID PCBINES
Guanine
(counts/mm/ftmole)
*AMP-C14 (2 .0 Mmoles;4 .5 X IO4 (counts/ 478
218
min/Vmole)
AMP-C1M-2.0 /»moles
glycine
467
210
»GMP-C14(2.0 /»moles;
7. 4X103 (counts/
8
368
min//imole)
GMP-C14+2.0 Amólesglycine
8
362
* These were prepared as described in an accompanying
paper (6).
in all four tumors, whereas xanthine and xanthosine (except for the latter in Sarcoma 180) were
not. (¿)Addition of certain compounds, particu
larly D-AMP and xanthine, resulted in a markedly
high incorporation of glycine-2-C14 into some
tumors.
Dilution of glycine-S-C1* incorporation into
Sarcoma 180 cells by D-AMP.—The dilution of
glycine incorporation into Sarcoma 180 nucleic
*We wish to acknowledge the assistance of Mrs. Dorothy
acids by D-AMP permitted a test of the role of
McManus and Mrs. Myrtle Gilboe in the determination of
inosine and hypoxanthine in the diluting effect of
radioactivity.
Downloaded from cancerres.aacrjournals.org on June 16, 2017. © 1958 American Association for Cancer Research.
Vol. 18, June, 1958
Cancer Research
550
adenine compounds. With Ehrlich ascites cells,
significantly larger amounts of acid-soluble inosine
and hypoxanthine were recovered from flasks con
taining glycine +1-0 /rmole AMP, adenosine, or
deoxyadenosine than from control flasks with only
glycine, and these three compounds were good
diluents. D-AMP did not dilute glycine incorpo
ration in Ehrlich cells, and levels of insosine and
hypoxanthine were not above those of the control
flasks. Table 3 includes some of the results with
Ehrlich cells from Edmonds and LePage (2) for
comparative purposes, and shows that the acidsoluble extracts of Sarcoma 180 cells, unlike those
from Ehrlich cells, contained significantly larger
amounts of inosine and hypoxanthine with added
D-AMP. Thus, the dilution of glycine incorpora
tion in Sarcoma by D-AMP could be correlated
with a formation of extra inosine and hypoxan
thine.
Additional data from the same experiment with
TABLE2
EFFECTOFPREFORMED
FURINECOMPOUNDS
ON60-MiNUTE
INCORPORATION
OF
GLYCINE-2-C1* INTO NUCLEIC ACIDS OF ASCITES TüMORCELLS
SP. ACT. WITH GLYCINE-2-C"
+ PüHINE COMPOUND*
WITH8CSHEDAdenine.16.22.29.751.88.30.241.14.81.89.901.291.221.51Guanine.82.92.95.971.64.67.581.02
SP. ACT.
GLYCINE-2-C»
2.0 JiMOLES
OfCOMPOUND
+1.0 (1HOLE8
TAS
LISTEDAdenineAdenosineD-AdenosineAMPD-AMPHypoxanthineIllusineGuanineGuanosineD-GuanosineGMPD-GMPXanthineXanthosineEhrlichAdenine.06f.88.48.241.0.12.74.75.67.70.961.121.06Guanine.12f.84.22
Adenine.02.15.36.871.65.24.19.55.75.631.89.74
* Duplicate flasks varied not more than 10 per cent from the mean.
t Values for the adenine series with Ehrlich cells were calculated from data in (2) and (4).
TABLE 3
RECOVERY
OFACID-SOLUBLE
INOSINE
ANDHYPOXANTHINE
IN EXPERIMENTS
WITHD-AMP
Inosine Hypoxanthine
(Amóles)0.07
Ehrlich cells
2.0 /imoles GIycine-2-C14
+1.0 AmólesAMP
+ 1.0 /miólesD-AMP
+1.0 /imoles D-Adenosine
Sarcoma 180 cells
2.0 MinólesGlycine-2-C14
+1.0 Minóles
D-AMP
Total radioactivity
inosine +hypozanthine
(counta/min)
0.21
0.02
0.110.05
0.48
0.03
0.100.0
1,600
6,520
1,120
3,090
0.220.04
0.35
800
9,970
TABLE 4
Sarcoma 180 cells are presented in Table 4.
D-AMP diluted incorporation into DNA purines
more than into RNA purines. Dilution of acid2.0 AmólesGlycine-2-C1* soluble AMP was not as great as dilution of RNA
2.0 /imoles
D-AMP(counts/min//imole)24390654No
1.0 gniole
ComponentisolatedRNA
adenine. At least a part of the greater dilution of
radioactivity entering RNA might be explained
adenineRNA
by considering two effects which could result from
guanineDNA
the increased size of the inosine-hypoxanthine pool
adenineDNA
guanineAS-AMPAS-ADPAS-GMPGlycine-2-C«(counts/min/Vmole)1,4703,3505142,08025,00024,800130,000+
act.9,97011,60045
meas.
when D-AMP was added. Since the specific activi
ty of this larger pool was as high as that of the
smaller inosine-hypoxanthine pool from control
,300
DILUTION
OFGLYciNE-2-C14
INCORPORATION
INTOSARCOMA
180BYD-AMP
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WILLIAMSANDLEPAGE—PurineMetabolism in Ascites Tumor Cells. I
flasks, these two metabolites were evidently acting
as traps for radioactivity from glycine-2-C14 and
thus decreasing the carbon-14 entering other acidsoluble nucleotide pools. In addition to diluting
radioactivity in acid-soluble nucleotides by a
carbon-14 trapping mechanism, the increased con
centrations of inosine and hypoxanthine could
affect the concentrations of various metabolites in
the de novo and preformed pathways and thereby
influence the rates of reactions leading to incor
poration of nucleotides into nucleic acids.
Glycine incorporation into RNA and DNA of
Ta3 ascites cells.—Theeffect of purine nucleotides
551
Acid-soluble extracts examined previously had
been from tests with exogenous compounds which
diluted or had no effect on glycine incorporation
in the particular tumor studied. It was thus de
cided to examine an acid-soluble extract from a
test in which a compound had increased incorpo
ration into a nucleic acid purine. The acid-soluble
extract from the duplicate flasks containing exog
enous GMP was compared with the extract from
the control containing glycine-2-C14 alone. As
shown in Table 6, specific activities of acid-soluble
AMP and ADP were not diluted by exogenous
GMP. In fact, although differences were too small
TABLE5
EFFECTOFPREFORMED
FURINECOMPOUNDS
ON60-MiNUTEINCORPORATION
OF
GLYCINE2-C14INTORNA ANDDNA OFTA3 ASCITESCELLS
2.0 pUOLES
GLYCINE-2-C"
RNA
ADEXINE
counts/min/fimole
DNA
ADENINE
counts/m ¡n/pmole
393
217
2.0 AmólesGlycine-2-C"
-t-1.0 pmolea of com
pound listed
AMP
D-AMP
GMP
D-GMP
RNA
DNA
GUANINE
(il AMM
counts/min/nmole
920
counts/min/pmole
«17
Sp. act. with glycine-2-C14 + purine compound
Sp. act. with glycine-2-C»
.54
1.85
1.48
1.28
TABLE
.16
.66
24
.88
.40
.37
2.72
.85
.88
.96
.85
.55
6
EFFECTOFGMP ONINCORPORATION
OFGLYciNE-2-CuINTOACID-SOLUBLE
PURINECOMPOUNDS
OFTA3 ASCITESCELLS
2.0 HMOLES GLTCINE-2-C"
2.0 ,.:•(>!,. GLTCINE-2-C"
(counts/min//imole)20,20019,20073
COMPONENT
ISOLATED
AMP
ADP
GMP
Inosine+hypoxanthine
Xanthosine+xanthine
L'ric acid
,10016,50041
+ 1.0 pMOLES UNLABELED GMP
(counts/min//¿mole)26,30023,00030
,90018
,40023,80024,500Totalcounta/min1,7551,0704,5106343,1301,050
,50043
,600Totalcounts/min1,5008802,1805451,690780
and deoxynucleotides on incorporation of glycine2-C14 into RNA and DNA was tested with TA3
cells. As shown in Table 5, the specific activity of
DNA adenine was diluted more than that of RNA
adenine by all four compounds tested; in fact,
incorporation into RNA adenine was higher with
added D-AMP, GMP, and D-GMP than with
glycine-2-C14 alone. AMP and D-AMP diluted in
corporation into DNA guanine more than into
RNA guanine; GMP diluted each to the same
extent and D-GMP diluted incorporation into
RNA guanine somewhat more than into DNA
guanine. Addition of GMP, D-GMP, or D-AMP
reduced the specific activity of DNA adenine but
increased the specific activity of RNA adenine.
Such an effect would be obscured in a test with
total nucleic acids.
to determine whether there was stimulation or no
change, the specific activities and total radioac
tivities were higher than those of the control, cor
responding to the results for the nucleic acid
purines. Total radioactivity in the inosine-hypoxanthine pool was not much higher than in the
control. Rather, extra radioactivity was being
trapped in the larger pools of xanthosine, xanthine, and uric acid present when GMP was added.
As discussed by Edmonds and LePage (2), the
"dilution effects" exerted by preformed purine
compounds on the incorporation of glycine-2-C14
into the ascites cell nucleic acids do not necessarily
represent simple dilution of the endogenous coun
terpart. Two major factors are probably involved :
(a) a dilution of radioactivity of the acid-soluble
adenine and guanine nucleotides or of compounds
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552
Cancer Research
Vol. 18, June, 1958
which are in equilibrium with them; (6) the effect
of increased concentrations of the exogenous purine compound on the rates of the various reac
tions in de novoand "preformed" pathways leading
to polynucleotide synthesis. As a hypothetical il
lustration of (6) : in the increase of specific activity
of RNA and acid-soluble AMP by exogenous
GMP (in T A3 ascites cells), the pool of added
GMP could reduce the reaction IMP —>
GMP and
favor the reaction IMP —»
AMP.
The incorporation of a "de novo precursor" has
been shown to pass through compounds associated
with the preformed pathway, particularly IMP,
AMP, GMP, and their di- and tri-phosphates (1).
The ascites tumors carry out a multiplicity of
reactions, both synthetic and degradative, and it
is difficult to assess the quantitative role of any
of these intermediates in the effects exhibited
nation of adenine and guanine nucleotides. These
relationships can be seen more readily in a dia
gram of the systems involved (Chart 2). Ehrlich
cells have been shown to maintain their adenine
pool at relatively constant levels by deamination
of added adenine compounds to hypoxanthine
compounds (2). Yet the larger pools of inosinehypoxanthine
or xanthosine-xanthine
formed
when unlabeled AMP or GMP was present with
glycine-2-C14 had about the same specific activi
ties as the smaller endogenous pools with radio
active glycine alone. Thus, glycine was still being
converted to purine compounds. When more AMP
(or GMP) was degraded to inosine-hypoxanthine
(or xanthosine-xanthine), a correspondingly greater
amount of radioactivity from the de novo precursor
entered this pool, presumably through IMP (or
XMP), rather than going to AMP (or GMP). The
larger pools of adenine or guanine nucleotides
would be expected to reduce the reaction IMP—»
\NOS1NE
AMP and XMP -> GMP. The animation systems
AMP
involved in converting IMP and XMP to AMP
DE NOVO
GLYCINEand GMP, and the systems converting the latter
PATHWAY
POLYNUCLEOTIDES
two nucleotides to polynucleotides are the ones
which appear to be saturated, with degradative
XMP
systems of apparently large capacity serving as
outlets to adjust pool sizes from both the pre
GMP
formed
and the de novo directions. It will be shown
XANTHOSINE
in the following paper (6) that only small amounts
CHART2.—Relationships of acid-soluble purine compounds
of IMP and XMP are present in the acid-soluble
in the conversion of glycine to nucleic acid polynucleotides.
pools of the ascites tumors studied, so that deami
when a certain preformed purine derivative is nation and dephosphorylation of the adenine and
added. Edmonds and LePage (2) have shown that guanine nucleotides must occur essentially at the
unlabeled AMP did not reduce the amount of same time.
Although glycine is still converted to purine
carbon-14 from orotic acid which reached uridylic
derivatives
when exogenous adenine and guanine
acid, when the orotic acid was incorporated simul
taneously with glycine-2-C14, which indicates that compounds are added, there could be a reduction
polynucleotide synthesis (or turnover) is not being in the rate, particularly at early time intervals. If
inhibited by the addition of exogenous purines. mechanism (6), a negative feedback, were operat
However, part of the dilution of radioactivity from ing, the inhibition would be thought to occur at
glycine into nucleic acids, particularly at early the first essentially irreversible step of the de novo
pathway, the conversion of phosphoribosylpyrotime periods, may well be from a preferential
utilization of the preformed purine compound. It phosphate to phosphoribosylamine. We have no
should be remembered that glycine did not affect evidence for such a feedback and consider mech
incorporation of AMP-C14 and GMP-C14 during a anism (a) more likely. However, it is worth while
to mention the second possibility in view of the
1-hour incubation period. Addition of the pre
recent
work on feedback inhibition in nucleic acid
formed compound could reduce the incorporation
of de novo precursors by either of two mechanisms, metabolism (3, 7).
As emphasized in the above discussion of mech
neither excluding the other: (a) saturation of
anisms, degradative reactions and products have
enzyme systems; (6) negative feedback.
an important part in the dilution effects. This is
In (a), various enzyme systems involved in con
verting acid-soluble nucleotides to nucleic acid especially illustrated by the studies with D-AMP
polynucleotides would be saturated by the added in Sarcoma 180 cells, which can convert that com
pound to inosine and hypoxanthine. The latter
preformed compound with a consequent disturb
ance of equilibria. The major adjustment made by two compounds were good diluents of glycine in
the ascites cells seems to be an increase in deami- corporation in all ascites tumors studied. Although
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WILLIAMSANDLEPAGE—PurineMetabolism in Ascites Tumor Cells. I
deamination products of guanine compounds were
not such good diluents, pools of these products
(xanthosine, xanthine, uric acid) accumulated
carbon-14, just as did the inosine-hypoxanthine
pools. In 60-minute incorporations of GMP-C14,
deamination products recovered from acid-soluble
extracts of Sarcoma 180 cells exceeded those from
6C3HED cells by threefold. In the dilution tests,
glycine incorporation into Sarcoma 180 was
strongly diluted by most of the compounds tested,
but much less dilution occurred in 6C3HED, par
ticularly with respect to dilution of incorporation
into one nucleic acid purine by derivatives of the
other purine. The greater capacity of the degradative enzyme systems in Sarcoma 180 would be
expected to result in a more rapid adjustment to
disturbance of pool sizes when exogenous purines
are added.
The greater dilution in specific activity of DNA
than of UNA with the Sarcoma 180 and TA3
ascites cells at 60 minutes, by both purine deoxyribose and purine ribose compounds, may be partly
a reflection of the extra steps before the preformed
precursors reach DNA. Probably a more impor
tant factor in the greater dilution of DNA, how
ever, is that relative changes in pool size upon
addition of exogenous purine compound would be
greater for the small pools of acid-soluble deoxynucleosides and deoxynucleotides than for the
larger pools of the corresponding ribose com
pounds.
The effects of the unlabeled purine compounds
on glycine-2-C14 incorporation differed among the
four types of ascites tumors, indicating differences
in enzymatic levels and perhaps in organization
and permeability of cell components.
SUMMARY
The effect of exogenous preformed purine com
pounds on the incorporation of glycine-2-C14 into
553
nucleic acids and acid-soluble nucleotides has been
investigated in four ascites tumors: Ehrlich,
Sarcoma 180, 6C3HED, and TA3. The action of
some of these compounds differed from one tumor
to another. The majority of compounds diluted
incorporation of glycine into nucleic acids, but a
few increased incorporation in some tumors. In
TA3 cells, several of the compounds increased in
corporation into UNA and decreased that into
DNA.
Acid-soluble adenine and guanine nucleotides
showed the same effect (i.e., dilution or increase of
specific activity) as the corresponding nucleic acid
purine. Deamination products of adenine and gua
nine played an important role in magnitude of
dilution, the pools of these compounds acting as
traps for the carbon-14 from glycine-2-C14. Pos
sible mechanisms involved in the effects of pre
formed purine compounds on de novo purine syn
thesis have been discussed.
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Downloaded from cancerres.aacrjournals.org on June 16, 2017. © 1958 American Association for Cancer Research.
Purine Metabolism in Mouse Ascites Tumor Cells: I. Effect of
Preformed Purines on in Vitro Incorporation of Glycine-2-C14
Anna Maria Williams and G. A. LePage
Cancer Res 1958;18:548-553.
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