Correlation of nucleotides and carbohydrates metabolism with pro-oxidant and antioxidant systems of erythrocytes depending on age in patients with colorectal cancer
Aim: To examine the relationship between metabolic features of purine nucleotides and antioxidant system depending on the age of patients with colorectal cancer. Materials and Methods: The activity of adenosine deaminase, xanthine oxidase, glutathione peroxidase, superoxide dismutase and glucose-6-p...
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| Опубліковано в: : | Experimental Oncology |
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| Дата: | 2014 |
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2014
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| Цитувати: | Correlation of nucleotides and carbohydrates metabolism with pro-oxidant and antioxidant systems of erythrocytes depending on age in patients with colorectal cancer / S.A. Zuikov, B.G. Borzenko, O.P. Shatova, E.M. Bakurova, G.E. Polunin // Experimental Oncology. — 2014. — Т. 36, № 2. — С. 17-120. — Бібліогр.: 24 назв. — англ. |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine| _version_ | 1860077486437564416 |
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| author | Zuikov, S.A. Borzenko, B.G. Shatova, O.P. Bakurova, E.M. Polunin, G.E. |
| author_facet | Zuikov, S.A. Borzenko, B.G. Shatova, O.P. Bakurova, E.M. Polunin, G.E. |
| citation_txt | Correlation of nucleotides and carbohydrates metabolism with pro-oxidant and antioxidant systems of erythrocytes depending on age in patients with colorectal cancer / S.A. Zuikov, B.G. Borzenko, O.P. Shatova, E.M. Bakurova, G.E. Polunin // Experimental Oncology. — 2014. — Т. 36, № 2. — С. 17-120. — Бібліогр.: 24 назв. — англ. |
| collection | DSpace DC |
| container_title | Experimental Oncology |
| description | Aim: To examine the relationship between metabolic features of purine nucleotides and antioxidant system depending on the age of patients with colorectal cancer. Materials and Methods: The activity of adenosine deaminase, xanthine oxidase, glutathione peroxidase, superoxide dismutase and glucose-6-phosphate dehydrogenase, the NOx concentration and the oxidative modification of proteins were determined spectrophotometricaly in 50 apparently healthy people and 26 patients with colorectal cancer stage III–IV, aged 40 to 79 years. Results: Increase of pro-oxidant system of erythrocytes with the age against decrease in level of antioxidant protection in both healthy individuals and colorectal cancer patients was determined. A significant increase of products of oxidative proteins modification in erythrocytes with ageing was shown. Statistically significant correlation between enzymatic and non enzymatic markers pro-oxidant system and the activity of antioxidant defense enzymes in erythrocytes of patient with colorectal cancer was determined. Conclusion: Obtained results have demonstrated the imbalance in the antioxidant system of erythrocytes in colorectal cancer patients that improve the survival of cancer cells that is more distinctly manifested in ageing. Key Words: age, colorectal cancer, erythrocyte, nucleotides, antioxidants, oxidative stress.
|
| first_indexed | 2025-12-07T17:14:09Z |
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| fulltext |
Experimental Oncology 36, 117–120, 2014 (June) 117
CORRELATION OF NUCLEOTIDES AND CARBOHYDRATES
METABOLISM WITH PRO-OXIDANT AND ANTIOXIDANT SYSTEMS
OF ERYTHROCYTES DEPENDING ON AGE IN PATIENTS
WITH COLORECTAL CANCER
S.A. Zuikov 1,* , B.G. Borzenko 1 , O.P. Shatova 1 , E.M. Bakurova 1 , G.E. Polunin 2
1 Department of Chemistry, Maksim Gorky National Medical University, Donetsk 83003, Ukraine
2 Department of General Surgery and Surgical Diseases, Maksim Gorky National Medical University,
Donetsk 83003, Ukraine
Aim: To examine the relationship between metabolic features of purine nucleotides and antioxidant system depending on the age
of patients with colorectal cancer. Materials and Methods : The activity of adenosine deaminase, xanthine oxidase, glutathione
peroxidase, superoxide dismutase and glucose-6-phosphate dehydrogenase, the NOx concentration and the oxidative modification
of proteins were determined spectrophotometricaly in 50 apparently healthy people and 26 patients with colorectal cancer
stage III– IV, aged 40 to 79 years. Results: Increase of pro-oxidant system of erythrocytes with the age against decrease in level
of antioxidant protection in both healthy individuals and colorectal cancer patients was determined. A significant increase of pro-
ducts of oxidative proteins modification in erythrocytes with ageing was shown. Statistically significant correlation between enzy-
matic and non enzymatic markers pro-oxidant system and the activity of antioxidant defense enzymes in erythrocytes of patient
with colorectal cancer was determined. Conclusion: Obtained results have demonstrated the imbalance in the antioxidant system
of erythrocytes in colorectal cancer patients that improve the survival of cancer cells that is more distinctly manifested in ageing.
Key Words: age, colorectal cancer, erythrocyte, nucleotides, antioxidants, oxidative stress.
It is known that ageing is accompanied by the dete-
rioration of protective functions of the organism and we-
akening of antioxidant defense (AOD). The metabolism
of carbohydrates, proteins and nucleotides is underwent
changes, in particular amplification of catabolic pro-
cesses is observed resulting in the accumulation of toxic
substances, including carcinogens, that is promoted
by reactive oxygen species (ROS) [1, 2]. Mentioned
processes are significantly amplified with ageing that
indicates the necessity to concentrate the attention
on the peculiarities of tumor growth in older patients.
Colorectal cancer (CC) — is a widespread patho-
logy in the world; among the CIS countries the high-
est incidence of disease is observed in Ukraine [3].
Number of patients suffering from CC is growing
steadily. This type of cancer takes one of the first
places on mortality in Cancer Registry among men
and women [4]. Among the methods for cancer
treatment, surgery supplemented with chemothera-
peutic drugs [5] remains currently the main one.
But the question of the use of antioxidants and pro-
oxidants in the treatment of oncology patients has not
been fully explored [6].
The objective of this work is to determine the acti vity
of key enzymes of purine nucleotides decomposition —
adenosine deaminase (ADA) and xanthine oxidase (XO),
as sources of ROS formation [7] (Figure), as well as non-
en zymic representative of pro-oxidant system (POS) —
nitric oxide (NO) [8]. For study the antioxidant level
of protection, we have determined the activity of key
enzymes of AOD: superoxide dismutase (SOD) and
glutathione peroxidase (GPO) [9], as well as the acti-
vity of the regulatory enzyme of the pentose phosphate
pathway (PPP) of carbohydrates conversion — glucose-
6-phosphate dehydrogenase (G6PDH).
Figure. Schematic representation of the purine nucleotides
decomposition
As an indicator of the intensity of the oxidative modifi-
cation of proteins (OMP), we have determined the content
of ketone dinitrophenylhydrazones (KDNPH) and alde-
hyde dinitrophenylhydrazones (ADNPH) of the neutral
and basic character. This is one of the earliest and most
stable indicators of lesions of various tissues and cells
of the body during the intensification of free-radical oxi-
dation and oxidation of thiol proteins [10]. We determined
the values of these parameters in erythrocytes to study
the effect of POS and antioxidant system (AOS) in different
age groups under normal conditions and in case of CC.
MATERIALS AND METHODS
The determination of mentioned indices was con-
ducted in hemolysate of erythrocytes received by double
freezing of washed erythrocytes. 26 pati ents aged
40–79 years with adenocarcinoma of the rectum III–IV stage
Submitted: January 13, 2014.
*Correspondence: E-mail: 83chem@mail.ru
Abbreviations used : ADA — adenosine deaminase; ADNPH — aldehyde
dinitrophenylhydrazones; AOD — antioxidant defense; AOS — antioxi-
dant system; CC — colorectal cancer; G6PDH — glucose-6-phosphate
dehydrogenase; GPO — glutathione peroxidase; KDNPH — ketone
dinitrophenylhydrazones; NO — nitric oxide; OMP — oxidative modifica-
tion of proteins; ONOO − — peroxynitrite; POS — pro-oxidant system;
PPP — pentose phosphate pathway; ROS — reactive oxygen species;
SOD — superoxide dismutase; XO — xanthine oxidase.
Exp Oncol 2014
36, 2, 117–120
118 Experimental Oncology 36, 117–120, 2014 (June)
were examined. The control group consisted of 50 condi-
tionally healthy middle-aged and elderly people without
pathologies of the gastrointestinal tract or other severe
systemic pathology. All examined people were divided
into two groups depending on their age: the first age
group — 40–59 years, the second — 60–79 years.
The study is conformable to the ethical principles
for clinical trials and the provisions of the Helsinki
Declaration of the World Medical Association and elimi-
nates infringing the interests of the patient and damage
of his health (Commission on Bioethics of Maxim Gorky
National Medical University, Donetsk).
ADA activity was determined by changing the
optical density of the reaction mixture at a wave-
length of 265 nm due to the accumulation of inosine
during hydrolytic decomposition of adenosine [11].
Determination of activity of XO is based on the ability
of the enzyme to generate superoxide anion radi-
cal, the content of which was determined by the rate
of recovery of nitro blue tetrazolium to formazan [12].
Endogenous level of NO in the form of nitrite anion
(NO 2
− ) after enzymatic recovery of nitrates to nitrites
was determined by means of standard Griess reac-
tion and designated as NO х [13]. SOD activity was
determined by inhibition of adrenaline autooxidation
with adrenochrome formation. GPO activity was deter-
mined by the rate of oxidation of reduced glutathione
according to the method of Moin [14]. G6PDH acti vity
was determined by increase of NADPH [15]. OMP
was evaluated by the method of R.L. Levine modified
by Е.Е. Dubinina [16], OMP products were registered
spectrophotometrically at different wavelengths:
356 nm and 430 nm — aliphatic KDNPH of neutral
and basic character; 370 nm and 530 nm — aliphatic
ADNPH of neutral and basic character. The level
of OMP products was given μmol 2,4-dinitrophenyl-
hydrazones generated per 1 mg of erythrocytes
protein. Determination of total protein was performed
according to the procedure described by Lowry [17].
Identification of all parameters was performed spectro-
photometrically (a spectrophotometer Specord-200).
Statistical data processing was performed using
the program “Statistica 10.0” Statsoft. Shapiro — Wilk
W test was used for checking normality of data dis-
tribution. Correlation analysis was performed using
Spearman’s rank correlation test.
RESULTS AND DISCUSSION
During the study of the control group (conditi-
onally healthy), we discovered a significant decrease
with age of enzymatic activities of: ADA, SOD, GPO,
NADPH in erythrocytes, whereas the activity of XO with
age did not show statistically significant changes.
Furthermore, a significant increase in the level of NO x
in the group of elderly people was observed (Table 1).
The obtained data indicate weakening of cellular
AOS: decrease in concentration of reduced glutathi-
one (as activity of G6PDH is decreased, which means
that formation of NADPH was decreased), increase
in the oxidation of thiol groups of enzymes leads
to weakening of AOD of erythrocytes and to changing
in their metabolism with age. At the same time, in-
crease of OMP products with age was discovered
(Table 2), which is another reason for the inhibition
of enzymatic link of the AOD system. It contributes
to enhancement of oxidative stress [18].
Table 1. Markers of decomposition of purines, POS and AOS in erythro-
cytes depending on age (M ± m)
Markers 40–59 years (n = 29) 60–79 years (n = 21)
NO x (mmol/l) 2.95 ± 0.22 3.65 ± 0.24*
ADA (nmol/min·mg) 12.1 ± 0.28 9.7 ± 0.24**
XO (μmol/min·mg) 5.9 ± 0.19 5.75 ± 0.22
G6PDH (nmol/min·mg) 0.42 ± 0.04 0.33 ± 0.03*
SOD (u/mg) 9.3 ± 0.22 7.45 ± 0.21*
GPO (μmol/min·mg) 421.0 ± 7.45 364.0 ± 13.8**
Note : *marker values are reliable when p < 0.05; **marker values are reli-
able when p < 0.001
Table 2. Level of OMP products in erythrocytes depending on age
(μmol/mg; M ± m)
Age groups
(years)
Wavelengths at which the OMP products were recorded
356 nm
KDNPH
(neutral)
370 nm
ADNPH
(neutral)
430 nm
KDNPH
(basic)
530 nm
ADNPH
(basic)
40–59 (n=29) 8.08 ± 0.03 7.30 ± 0.05 5.51 ± 0.06 4.07 ± 0.02
60–79 (n=21) 8.38 ± 0.03* 7.68 ± 0.06* 5.98 ± 0.09* 4.73 ± 0.05*
Note : *marker values are reliable when p < 0.001
After the correlation analysis of changes in the pa-
rameters of the erythrocytes depending on age,
we determined the statistically significant negative
correlation of ADA with NO x ( rho = 0.33, p = 0.020),
i.e., decrease of ADA in erythrocytes and increase
of NO acts as a protective mechanism activated
in conditions of hypoxia [19]. Also positive correla-
tions of ADA with SOD ( rho =0.67; p=0.0003), ADA
with GPO ( rho = 0.46; p = 0.001), GPO with G6PDH
( rho = 0.49; p = 0.001) were discovered, thus pointing
to the coordinated operation of enzymatic link of the
AOD system. It is of particular interest to note that with
age in control group, enzymatic markers of POS and
AOD decrease, but non-enzymatic markers of POS
significantly increase. Thus, age is one of the deter-
mining factors in the correlation of AOD with POS.
In the study of patients with CC in the second age
group (with respect to the first one), the decrease
of the activities of ADA, GPO and G6PDH was shown,
while SOD activity was not significantly changed
(Table 3).
Table 3. Markers of decomposition of purines, POS and AOS in erythro-
cytes in patients with CC depending on age (M ± m)
Markers 40–59 years (n = 10) 60–79 years (n = 16)
NO x (mcmol/l) 9.2 ± 0.41 13.1 ± 0.81*
ADA (nmol/min·mg) 5.4 ± 0.19 4.3 ± 0.24*
XO (μmol/min·mg) 7.7 ± 0.16 12.3 ± 0.51**
G6PDH (nmol/min·mg) 0.23 ± 0.04 0.15 ± 0.03*
SOD (u/mg) 11.6 ± 0.44 12.1 ± 0.45
GPO (μmol/min·mg) 203.0 ± 8.25 154.0 ± 2.95**
Note : *marker values are reliable when p < 0.05; **marker values are reli-
able when p < 0.001
At the same time, in the enzymatic and non-enzy-
matic link of POS, increase in the activity of XO and
NO x levels with age, as well as increase in OMP
level in erythrocytes of patients from the second age
group (Table 4) was identified. Therefore, it can be as-
sumed that there is an enhancement of OMP in eryth-
rocytes of older patients with CC, that is accompanied
Experimental Oncology 36, 117–120, 2014 (June) 119
by changes in the intensity of metabolic processes
of the organism and, therefore, further exacerbates
the development of oxidative stress. Erythrocytes are
highly sensitive to oxidative stress because of contact
with high O 2 concentrations. It may result in the auto-
oxidation of hemoglobin, peroxidation of membrane
lipids followed by impairment of erythrocyte mem-
brane and limited erythrocyte capability to repair
mentioned injuries.
Table 4. Level of OMP products in erythrocytes in patients with CC depending
on age (μmol/mg; M ± m)
Age groups
(years)
Wavelengths at which the OMP were recorded
356 nm
KDNPH
(neutral)
370 nm
ADNPH
(neutral)
430 nm
KDNPH
(basic)
530 nm
ADNPH
(basic)
40–59 (n=10) 10.6 ± 0.15 9.79 ± 0.09 8.38 ± 0.07 6.63 ± 0.12
60–79 (n=16) 12.1 ± 0.14* 10.6 ± 0.10* 9.49 ± 0.08* 7.52 ± 0.09*
Note : *marker values are reliable when p < 0.001
During the comparative analysis of the mentioned
parameters in CC patients, there were established
statistically significant relationships for: NO x and XO
( rho = 0.44; p = 0.032), NO x and ADA ( rho = −0.49;
p = 0.014) and GPO and XO ( rho = −0.72; p = 0.0001).
The decrease in the activity of ADA in erythrocytes
combines with hypoxia is typical for CC. It keeps ex-
tracellular adenosine level, thus acting as an adaptive
mechanism of cells protection activated in conditions
of hypoxia and stimulating increase in production
of NO [20]. It is known that the cellular effect of NO de-
pends on the ratio of the concentration of NO and
superoxide anion radical in a cell. NO and superoxide
anion radical individually are inducers of apopto-
sis. However, simultaneous increase in the activity
of XO and NO levels observed by us in the older age
group of patients with CC contributes to the formation
of peroxynitrite (ONOO − ), thus acting as a protective
mechanism of a tumor cell from the cytotoxic action
of these metabolites. Furthermore, in comparison
with superoxide anion radical ONOO − is even more
powerful oxidizing agent capable of oxidizing both
NH- and SH-groups of proteins [21]. This oxidation
leads to inactivation of certain enzymes, one of which
is SOD, as well as GPO — involved in the deactiva-
tion of peroxynitrites with formation of thiol radicals
of glutathione (GS). As a result, the last of antioxidants
is transformed into prooxidant [22]. This, in its turn,
is consistent with the data obtained on decrease
in the activity of G6PDH in erythrocytes accumulating
NADPH for recovery of glutathione.
We also discovered direct correlation of OMP with
NO x products ( rho = 0.49; p = 0.041), OMP with XO
( rho = 0.62; p = 0.008), while activities of enzymatic
markers of AOD negatively and significantly corre-
late with the level of protein oxidation products: GPO
with OMP ( rho = −0.67; p = 0.003), G6PDH with OMP
( rho = −0.51; p = 0.011). The observed increase in NO x
and OMP with age in conditions of simultaneous de-
crease of enzymes of antioxidant level of protection
is an indication of strengthening of pro-oxidant status
of erythrocytes. Therefore, in erythrocytes of older pa-
tients with CC, restructuring of the antiradical protection
system is observed. This restructuring is closely related
to changes in the metabolism of nucleotides. It is known
that in healthy cells and cells of benign tumors, oxidizers
contribute to increase in cell proliferation, while antioxi-
dants inhibit it, thus acting as a signal that controls cell
division [23]. By contrast to this, in cells of malignant
tumors, wherein the oxidative stress is characterized
by even more expressed manifestation, antioxidants
help tumor cells to proliferate and survive by protecting
them from apoptosis. But excess of the ROS can also
irreversibly damage the regulatory proteins and nucleic
acid molecules, thereby contributing to enhancement
of metastasing of tumor cells [24].
Thus, determined malfunctions of AOD in erythro-
cytes have age-related features, which are aggravated
in case of tumor pathology, affecting the viability of a tu-
mor cell and its functional full-value, which is more typi-
cal in the late stages of the disease. Such malfunctions
lead to an imbalance between the POS and AOS, which
are closely related to enzymatic changes in the metabo-
lism of carbohydrates and nucleotides, contributing
to strengthening of each other on the principle of feed-
back, which in its turn leads to the development of oxi-
dative stress and as a consequence — to the structural
modification, primarily, of biomembranes, enzymes,
and nucleotides. Intensity of metabolic processes and
pathogenetic restructuring at the cellular level in their
turn depend on the severity of these disorders. There-
fore, the balance between oxidants and antioxidants
is a key issue in the development of cancer, which
remains topical up to the present.
CONFLICTS OF INTEREST
The authors declare that they have no competing
interests.
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Copyright © Experimental Oncology, 2014
|
| id | nasplib_isofts_kiev_ua-123456789-145341 |
| institution | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| issn | 1812-9269 |
| language | English |
| last_indexed | 2025-12-07T17:14:09Z |
| publishDate | 2014 |
| publisher | Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| record_format | dspace |
| spelling | Zuikov, S.A. Borzenko, B.G. Shatova, O.P. Bakurova, E.M. Polunin, G.E. 2019-01-20T18:03:26Z 2019-01-20T18:03:26Z 2014 Correlation of nucleotides and carbohydrates metabolism with pro-oxidant and antioxidant systems of erythrocytes depending on age in patients with colorectal cancer / S.A. Zuikov, B.G. Borzenko, O.P. Shatova, E.M. Bakurova, G.E. Polunin // Experimental Oncology. — 2014. — Т. 36, № 2. — С. 17-120. — Бібліогр.: 24 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/145341 Aim: To examine the relationship between metabolic features of purine nucleotides and antioxidant system depending on the age of patients with colorectal cancer. Materials and Methods: The activity of adenosine deaminase, xanthine oxidase, glutathione peroxidase, superoxide dismutase and glucose-6-phosphate dehydrogenase, the NOx concentration and the oxidative modification of proteins were determined spectrophotometricaly in 50 apparently healthy people and 26 patients with colorectal cancer stage III–IV, aged 40 to 79 years. Results: Increase of pro-oxidant system of erythrocytes with the age against decrease in level of antioxidant protection in both healthy individuals and colorectal cancer patients was determined. A significant increase of products of oxidative proteins modification in erythrocytes with ageing was shown. Statistically significant correlation between enzymatic and non enzymatic markers pro-oxidant system and the activity of antioxidant defense enzymes in erythrocytes of patient with colorectal cancer was determined. Conclusion: Obtained results have demonstrated the imbalance in the antioxidant system of erythrocytes in colorectal cancer patients that improve the survival of cancer cells that is more distinctly manifested in ageing. Key Words: age, colorectal cancer, erythrocyte, nucleotides, antioxidants, oxidative stress. en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Experimental Oncology Original contributions Correlation of nucleotides and carbohydrates metabolism with pro-oxidant and antioxidant systems of erythrocytes depending on age in patients with colorectal cancer Article published earlier |
| spellingShingle | Correlation of nucleotides and carbohydrates metabolism with pro-oxidant and antioxidant systems of erythrocytes depending on age in patients with colorectal cancer Zuikov, S.A. Borzenko, B.G. Shatova, O.P. Bakurova, E.M. Polunin, G.E. Original contributions |
| title | Correlation of nucleotides and carbohydrates metabolism with pro-oxidant and antioxidant systems of erythrocytes depending on age in patients with colorectal cancer |
| title_full | Correlation of nucleotides and carbohydrates metabolism with pro-oxidant and antioxidant systems of erythrocytes depending on age in patients with colorectal cancer |
| title_fullStr | Correlation of nucleotides and carbohydrates metabolism with pro-oxidant and antioxidant systems of erythrocytes depending on age in patients with colorectal cancer |
| title_full_unstemmed | Correlation of nucleotides and carbohydrates metabolism with pro-oxidant and antioxidant systems of erythrocytes depending on age in patients with colorectal cancer |
| title_short | Correlation of nucleotides and carbohydrates metabolism with pro-oxidant and antioxidant systems of erythrocytes depending on age in patients with colorectal cancer |
| title_sort | correlation of nucleotides and carbohydrates metabolism with pro-oxidant and antioxidant systems of erythrocytes depending on age in patients with colorectal cancer |
| topic | Original contributions |
| topic_facet | Original contributions |
| url | https://nasplib.isofts.kiev.ua/handle/123456789/145341 |
| work_keys_str_mv | AT zuikovsa correlationofnucleotidesandcarbohydratesmetabolismwithprooxidantandantioxidantsystemsoferythrocytesdependingonageinpatientswithcolorectalcancer AT borzenkobg correlationofnucleotidesandcarbohydratesmetabolismwithprooxidantandantioxidantsystemsoferythrocytesdependingonageinpatientswithcolorectalcancer AT shatovaop correlationofnucleotidesandcarbohydratesmetabolismwithprooxidantandantioxidantsystemsoferythrocytesdependingonageinpatientswithcolorectalcancer AT bakurovaem correlationofnucleotidesandcarbohydratesmetabolismwithprooxidantandantioxidantsystemsoferythrocytesdependingonageinpatientswithcolorectalcancer AT poluninge correlationofnucleotidesandcarbohydratesmetabolismwithprooxidantandantioxidantsystemsoferythrocytesdependingonageinpatientswithcolorectalcancer |