DNA damage in tumor cells and peripheral blood lymphocytes of endometrial cancer patients assessed by the comet assay
To date, genome instability is considered to be a common feature not only of tumor cells, but also of non-malignant cells of cancer patients, including peripheral blood lymphocytes (PBLs). The issue of the association between genome instability in tumor cells and PBLs, as well as of its relationship...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
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| Cite this: | DNA damage in tumor cells and peripheral blood lymphocytes of endometrial cancer patients assessed by the comet assay / L.G. Buchynska, O.V. Brieieva, N.P. Iurchenko, V.V. Protsenko, S.V. Nespryadko // Experimental Oncology. — 2017 — Т. 39, № 4. — С. 299–303. — Бібліогр.: 35 назв. — англ. |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine| _version_ | 1860096967061798912 |
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| author | Buchynska, L.G. Brieieva, O.V. Lurchenko, N.P. Protsenko, V.V. Nespryadko, S.V. |
| author_facet | Buchynska, L.G. Brieieva, O.V. Lurchenko, N.P. Protsenko, V.V. Nespryadko, S.V. |
| citation_txt | DNA damage in tumor cells and peripheral blood lymphocytes of endometrial cancer patients assessed by the comet assay / L.G. Buchynska, O.V. Brieieva, N.P. Iurchenko, V.V. Protsenko, S.V. Nespryadko // Experimental Oncology. — 2017 — Т. 39, № 4. — С. 299–303. — Бібліогр.: 35 назв. — англ. |
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| container_title | Experimental Oncology |
| description | To date, genome instability is considered to be a common feature not only of tumor cells, but also of non-malignant cells of cancer patients, including peripheral blood lymphocytes (PBLs). The issue of the association between genome instability in tumor cells and PBLs, as well as of its relationship with tumor progression remains poorly understood. Aim: To evaluate the level DNA damage in tumor cells and PBLs of endometrial cancer (EC) patients with regard to clinical and morphological characteristics of the patients. Materials and Methods: DNA damage was assessed in 106 PBLs samples and 42 samples of tumor cell suspension from EC patients by comet assay. PBLs from 30 healthy women were used as control. The level of DNA damage was expressed as the percentage of DNA in the comet tails (% tail DNA). Results: It was revealed that the amount of DNA damage in PBLs of EC patients was 2.2 times higher in comparison with that of healthy donors (8.3 ± 0.7 and 3.7 ± 0.4% tail DNA, respectively) (p < 0.05). In this study, no association between the levels of DNA damage in endometrial tumor cells and PBLs was observed (r = 0.11; p > 0.05). The amounts of DNA damage both in tumor cells and PBLs were not related to the degree of tumor differentiation as well as the depth of myometrial invasion, but depended on the body mass index (BMI) of EC patients: high level of lesions was observed in patients with elevated BMI values. Furthermore, the level of DNA damage in tumor cells was associated to familial aggregation of cancer and was significantly higher in endometrial cells from patients with family history of cancer vs that from EC patients with sporadic tumors (32.3 ± 2.9 and 22.8 ± 1.8% tail DNA, respectively) (p < 0.05). It was also found that for women who had high level of DNA damage in PBLs, the risk of EC was greater (odds ratio value of 3.5) compared to those with low level of such lesions. Conclusion: Genome instability that appears as an increased level of DNA damage in tumor cells and PBLs of EC patients is associated with BMI and family history of cancer and can reflect a predisposition to cancer.
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Experimental Oncology 39, 299–303, 2017 (December) 299
DNA DAMAGE IN TUMOR CELLS AND PERIPHERAL BLOOD
LYMPHOCYTES OF ENDOMETRIAL CANCER PATIENTS ASSESSED
BY THE COMET ASSAY
L.G. Buchynska1, O.V. Brieieva1, *, N.P. Iurchenko1, V.V. Protsenko1, S.V. Nespryadko2
1R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine,
Kyiv 03022, Ukraine
2National Cancer Institute, MH of Ukraine, Kyiv 03022, Ukraine
To date, genome instability is considered to be a common feature not only of tumor cells, but also of non-malignant cells of cancer
patients, including peripheral blood lymphocytes (PBLs). The issue of the association between genome instability in tumor cells
and PBLs, as well as of its relationship with tumor progression remains poorly understood. Aim: To evaluate the level DNA dam-
age in tumor cells and PBLs of endometrial cancer (EC) patients with regard to clinical and morphological characteristics of the
patients. Materials and Methods: DNA damage was assessed in 106 PBLs samples and 42 samples of tumor cell suspension from
EC patients by comet assay. PBLs from 30 healthy women were used as control. The level of DNA damage was expressed as the
percentage of DNA in the comet tails (% tail DNA). Results: It was revealed that the amount of DNA damage in PBLs of EC patients
was 2.2 times higher in comparison with that of healthy donors (8.3 ± 0.7 and 3.7 ± 0.4% tail DNA, respectively) (p < 0.05). In this
study, no association between the levels of DNA damage in endometrial tumor cells and PBLs was observed (r = 0.11; p > 0.05). The
amounts of DNA damage both in tumor cells and PBLs were not related to the degree of tumor differentiation as well as the depth
of myometrial invasion, but depended on the body mass index (BMI) of EC patients: high level of lesions was observed in patients
with elevated BMI values. Furthermore, the level of DNA damage in tumor cells was associated to familial aggregation of cancer
and was significantly higher in endometrial cells from patients with family history of cancer vs that from EC patients with sporadic
tumors (32.3 ± 2.9 and 22.8 ± 1.8% tail DNA, respectively) (p < 0.05). It was also found that for women who had high level of DNA
damage in PBLs, the risk of EC was greater (odds ratio value of 3.5) compared to those with low level of such lesions. Conclusion:
Genome instability that appears as an increased level of DNA damage in tumor cells and PBLs of EC patients is associated with
BMI and family history of cancer and can reflect a predisposition to cancer.
Key Words: DNA damage, tumor cells, peripheral blood lymphocytes, endometrial cancer, comet assay.
Today, it is well known that the formation and pro-
gression of malignant neoplasms are accompanied
by extensive molecular genetic changes. The presence
of various types of DNA damage and chromosomal
alterations is a characteristic feature of tumor cells [1].
According to modern notions, such changes are associ-
ated with genomic instability of malignant cells and reflect
the influence of exo- and endogenous DNA-damaging
factors, as well as defects in the functioning of the DNA
repair systems [1, 2]. Genome instability promotes the
emergence of genetic diversity, clonal evolution of tumor
cells and progression of the neoplastic process [3].
Modern studies indicate that endometrial carcinoma
is characterized by the presence of microsatellite and
chromosomal instability [4]. Moreover, endometrial
cells are constantly exposed to the genotoxic influence
of reactive oxygen species (ROS) resulting from meta-
bolic transformations of estrogens during the menstrual
cycle [5]. The elevated ROS level leads to the appear-
ance of a highly mutagenic 8-oxo-7,8-dihydro-2'-de-
oxyguanosine, DNA breaks, apurin sites and chromo-
somal alterations [6]. Furthermore, genome instability
of endometrial tumor cells may have hereditary origin,
in particular due to germline mutations in the mismatch
repair genes in the Lynch syndrome [7].
In recent years, numerous studies have been de-
voted to the problem of genome destabilization in ma-
lignant cells [8, 9]. However, today little is known about
how the deregulation of genome integrity maintenance
in carcinoma cells manifests at the systemic level, that
is, on the structural and functional features of other cells
in the body, including peripheral blood lymphocytes
(PBLs). Meanwhile, in recent years, the issue of the
possibility of using lymphocytes as surrogate markers
(cells) that reflect the molecular genetic changes in the
tumor is actively discussed [10–12].
A number of studies have shown that genome integ-
rity in the PBLs of patients with different forms of cancer
is disturbed [13–18]. Our previous study has revealed
that PBLs of endometrial cancer (EC) are characterized
by strong genome destabilization, in particular impaired
DNA repair, which is associated with family history of can-
cer [21]. However, the issue of the relationship between
genome instability in PBLs and tumor cells, as well as its
association with tumor progression and clinical charac-
teristics of patients with EC, remains insufficiently studied.
This study aims to analyze the association between
DNA damage in PBLs and tumor cells of EC patients.
In addition, the dependence of the degree of DNA dam-
age on the clinical and morphological characteristics
of patients and its significance to the risk of EC is studied.
MATERIALS AND METHODS
A total of 106 newly diagnosed, previously un-
treated patients with EC stages I and II were recruited
Submitted: October 04, 2017.
*Correspondence: E-mail: olha.brie@gmail.com
Abbreviations used: BMI — body mass index; EC — endometrial cancer;
PBLs — peripheral blood lymphocytes; ROS — reactive oxygen species.
Exp Oncol 2017
39, 4, 299–303
300 Experimental Oncology 39, 299–303, 2017 (December) Experimental Oncology 39, 299–303, 2017 (December) 301
tients had tumors of the female reproductive system,
gastrointestinal tract and lungs (Table 2). For further
analysis of DNA damage level in PBLs and tumor cells,
a group of EC patients with family history of cancer
was formed, which included women with clustering
of the female reproductive system and/or other Lynch-
associated tumor incidence in their pedigrees [7].
There was no statistically significant difference
in the amount of DNA damage between PBLs from
EC patients with family history of cancer compared
to those with no family history. However, it was found
that the level of DNA damage in tumor cells from
patients with family history of cancer significantly ex-
ceeded that in cells from patients with sporadic tumors
(32.3 ± 2.9 and 22.8 ± 1.8% tail DNA, respectively)
(p < 0.05) (Fig. 2).
0
5
10
15
20
25
30
35
40
PBLs Tumor cells
%
ta
il
DN
A
Patients with no family history of cancer
Patients with family history of cancer
p < 0.05
Fig. 2. DNA damage in PBLs and tumor cells of EC patients with
regard to family history of cancer
In order to assess the association between DNA
damage level in PBLs and EC risk, the OR value among
matched case and control groups (30 EC patients
and 30 healthy individuals) was calculated. According
to the obtained data, the median (Me) of % tail DNA
in PBLs was 3.7, on the basis of which all the examined
women were divided into groups with high (> Me) and
low (< Me) levels of DNA damage. It was found that for
women who had high level of DNA damage in PBLs,
the risk of EC was greater compared to those with low
level of such lesions (OR value of 3.5) (Table 3).
Table 3. Association between DNA damage in PBLs and EC risk
Level of DNA
damage
Group of examined women OR (95% CI)EC patients Controls
Low 11 10 3.5 (1.2–10.0)High 19 20
DISCUSSION
The issue of the occurrence and causes of genome
instability in PBLs of cancer patients has been ac-
tively investigated over recent years. Results of seve-
ral studies indicate a significant destabilization of the
genome in PBLs of cancer patients. In particular, high
level of baseline DNA damage was detected in patients
with malignant tumors of breast, ovary, prostate, lungs,
esophagus, bladder and kidney [13–20]. A number
of studies revealed the association between the level
of DNA damage in PBLs and risk of cancer [19, 20].
It is believed that an increased level of DNA dam-
age in PBLs and malignant cells may be caused by in-
fluence of environmental genotoxic factors as well
as substances released during metabolic processes
in cancer patients [2]. Very often, the effect of such
factors emerges through the action of ROS that, com-
bined with antioxidant system failure, leads to the de-
velopment of oxidative stress [6]. It is well-known that
ROS are characterized by pronounced DNA-damaging
properties. They can induce the appearance of single-
and double-stranded DNA breaks, highly mutagenic
8-oxo-7,8-dihydro-2'-deoxyguanosine and other
nucleotide modifications. It should be noted that today
the genotoxic influence of ROS is considered as one
of the possible mechanisms of carcinogenesis. In fact,
oxidative DNA damage caused by ROS is constantly
detected in malignant neoplasms of various localiza-
tions [23].
It is supposed that the main sources of endogenous
ROS are the reactions of cellular respiration, lipid
peroxidation and inflammation. Along with the latter,
the metabolic transformations of estrogens may have
a strong influence on the development of genome in-
stability in PBLs and tumor cells in EC patients, since
these processes are accompanied by the formation
of genotoxic intermediates — catechol estrogens,
quinones and semiquinones which can directly bind
DNA, leading to the occurrence of apurinic sites, or en-
ter the redox reactions with ROS production [26–28].
It is possible that the high level of DNA damage
in PBLs and tumor cells of EC patients with elevated
BMI values may be associated with hormonal effects
as far as adipose tissue is an important source of es-
trogen. In addition, elevated BMI values are related
to increased level of circulating proinflammatory cy-
tokines (TNFα, IL-1, IL-6, etc.) that can induce ROS
formation [29]. It is characteristic that Salinas et al.
revealed an elevated level of oxidative stress mark-
ers in the blood of EC patients with an increased BMI
value [30].
An increased level of DNA damage in tumor
cells in EC patients with family history of cancer can
be caused by hereditary defects in DNA repair genes
and tumor suppressors [7, 31–33]. Furthermore,
it is assumed that there are other molecular mecha-
nisms that determine hereditary predisposition to EC,
which may also be associated with the development
of genome instability [32, 33]. Thus, it was found that
the risk of developing hormone-dependent tumors
for the study. All EC patients underwent surgery
at the gynecological oncology department of the Na-
tional Cancer Institute, Kyiv, Ukraine. The mean age
of EC patients was 59.1 ± 1.6 years. The control group
consisted of 30 healthy women, matched on age and
menopausal status, with no previous or present his-
tory of cancer. All patients were thoroughly informed
about the study that was approved by the Committee
for Ethical Issues of the R.E. Kavetsky Institute of Ex-
perimental Pathology, Oncology and Radiobiology,
National Academy of Sciences of Ukraine.
Morphological analysis of tumors was performed
on haematoxylin and eosin stained sections. All pa-
tients had a histologically confirmed diagnosis of en-
dometrioid carcinoma. Information on family history
of cancer was obtained through the personal interview
based on a structured questionnaire.
Lymphocytes were isolated from venous blood
by density centrifugation using Ficoll-Hypaque gradi-
ent. To obtain tumor single cell suspensions, tumor
tissue was disrupted with a MEDI machine (Becton
Dickinson). After disaggregation of the tissue, the cell
suspensions were filtered to remove any tissue debris.
The viability of PBLs and tumor cells was determined
using the trypan blue exclusion test.
In order to evaluate baseline levels of DNA damage
in PBLs and tumor cells, single cell gel electrophoresis
assay (DNA comet assay) was performed as described
previously by Olive [22]. A suspension of lymphocytes
or tumor cells (1–2 × 105 cells/ml) was mixed with 1%
low melting point agarose (Sigma-Aldrich) at 37 °C, and
75 μl of this mixture was spread on slides precoated
with 1% normal melting point agarose (Sigma-Aldrich).
After solidification of the agarose, the slides were im-
mersed into lysis solution (2.5 M NaCl, 100 mM EDTA,
10 mM Tris base, 10% DMSO, 1% Triton X-100, pH 10).
Lymphocytes treated with 100 μM H2O2 for 5 min.
at 4 °C were used as a positive control. The lysis was
carried out in the dark for 1 h at 4 °C. Then, the slides
were transferred to the electrophoresis chamber and
incubated in alkaline solution (300 mM NaOH and
1 mM EDTA, pH > 13) for 20 min. Electrophoresis
was performed in the same solution at a voltage
of 0,8 V/cm for 20 min. After electrophoresis, the
slides were neutralized with 0,4 M Tris HCl solution
for 10 min, washed in distilled water 2 times for 5 min,
dried at 37 °C, stained with SYBR Green I and analyzed
with a fluorescence microscope. A total of 50 micro-
graphs per slide were assessed using the CometScore
software package (TriTek Corp.). The level of DNA
damage was expressed as the percentage of DNA
in the comet tails (% tail DNA).
Statistical analysis was performed using the
Statistica 8.0 software package (StatSoft, Inc.). The
Mann — Whitney U test was used to evaluate differences
between groups of EC patients and healthy women.
A p-value less than 0.05 was considered statistically
significant. Relationship between variables was deter-
mined using Spearman’s rank correlation coefficient (r).
Logistic regression was used to calculate odds ratios
(OR) and 95% confidence intervals (CI) for the associa-
tion between DNA damage level in PBLs and EC risk.
RESULTS
Large inter-individual difference in the level of DNA
damage in PBLs was observed in both healthy donors
and EC patients. At the same time, the range of this
parameter was wider in PBLs of EC patients (1.1–21.4%
tail DNA) than that of control samples (1.2–9.2% tail
DNA). On average, the level of DNA damage in PBLs
of EC patients was 8.3 ± 0.7% tail DNA that was
2.2 times higher in comparison with its degree in healthy
donors (3.7 ± 0.4% tail DNA) (p < 0.05). Analysis of the
level of DNA damage in malignant cells was carried out
on tumor tissue samples of 42 EC patients (7 — well,
19 — moderate and 16 — poorly differentiated tumors).
It was revealed that EC cells are characterized by a pro-
nounced amount of DNA damage, which averaged
26.4 ± 1.8% tail DNA with individual variations ranging
from 3.3 to 62.9% tail DNA (Fig. 1).
Fig. 1. Representative micrographs of comets derived from
PBLs of healthy individuals (a), EC patients (b) and endometrial
carcinoma cells (c)
To determine the possibility of using lymphocytes
as surrogate cells that reflect certain characteristics
of malignant cells, a correlation analysis was performed
between the levels of DNA damage in PBLs and endo-
metrial tumor cells. In this study, no association between
these parameters was observed (r = 0.11; p > 0.05).
Comparison of the level of genome instability with
clinical and morphological features of EC patients did
not reveal the relationship between DNA damage in PBLs
or tumor cells and the degree of tumor differentiation
as well as the depth of myometrial invasion (Table 1).
However, it was found that the level of DNA damage
in both PBLs and tumor cells depends on the body mass
index (BMI) of EC patients. Thus, individuals with BMI
values above the median (> 34.1 kg/m2) had significantly
higher levels of DNA damage than those with less obesity
(< 34.1 kg/m2) (p < 0.05) (Table 1). Therefore, increased
DNA damage in PBLs was observed in EC patients from
obesity class I (BMI 31.0–35.9 kg/m2).
Table 1. Comparison of DNA damage in PBLs and tumor cells with clinical
and morphological characteristics of EC patients
Characteristics
Level of DNA damage,
% tail DNA
PBLs Tumor cells
Degree of tumor
differentiation
Well differentiated 8.8 ± 3.6 26.1 ± 1.8
Moderately differentiated 8.7 ± 0.9 25.2 ± 3.2
Poorly differentiated 7.8 ± 1.2 25.8 ± 2.0
Depth of myome-
trial invasion
< ½ 8.6 ± 1.3 24.7 ± 3.1
> ½ 8.2 ± 0.9 26.1 ± 2.4
BMI < Me 5.8 ± 0.7 22.0 ± 1.9
> Me 8.6 ± 1.2* 29.2 ± 2.4*
Note: *significantly different from EC patients with BMI < Me (p < 0.05).
Pedigree analysis of all the EC patients revealed
the familial clustering of cancers in 37 cases (38.9%).
Most often, first and second degree relatives of EC pa-
Table 2. Familial aggregation of tumors in EC patients
Degree of relationship
Tumors localization and their quantity in families, n (%)
Female reproductive system Gastrointestinal
tract Lungs Others TotalEndometrium Ovary Breast
І (mother, father, sister, brother, children) 4 (5.4) 2 (2.7) 1 (1.4) 8 (10.7) 5 (6.8) 13 (17.5) 33 (45.6)
ІІ (aunt, uncle, grandmother, grandfather, nephew, niece) 3 (4.0) 2 (2.7) 7 (9.5) 9 (12.2) 1 (1.4) 19 (25.7) 41 (55.4)
Total number of relatives with malignant tumors 19 (25.7) 17 (22.9) 6 (8.2) 32 (43.2) 74 (100.0)
302 Experimental Oncology 39, 299–303, 2017 (December) Experimental Oncology 39, 299–303, 2017 (December) 303
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substances released by the tumor on adjacent tissues
and distant organs [23–25].
In conclusion, the results of the study indicate
a pronounced destabilization of the genome in PBLs
and tumor cells of EC patients, which may reflect
homeostasis disorders in these women. It was shown
that in both PBLs and tumor cells, the level of DNA
damage depends on the BMI of EC patients and in-
creases in cases with elevated values of this param-
eter. In addition, the dependence of the level of DNA
damage in endometrial carcinoma cells on familial
aggregation of cancers was detected: the amount
of DNA lesions was higher in EC patients with family
history of cancer. The presented data indicate the pos-
sibility of determining the risk of EC by DNA damage
level in PBLs. Specifically, the high amount of baseline
DNA damage in PBLs is associated with an increased
risk of EC. Further studies of PBLs of cancer patients
are needed in order to determine the role of genome
instability of somatic non-malignant cells in the patho-
genesis of the malignant disease. It is equally impor-
tant to ascertain the possibility of using lymphocytes
as surrogate cells that reflect the morphological and
functional characteristics of tumor cells.
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| id | nasplib_isofts_kiev_ua-123456789-138546 |
| institution | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| issn | 1812-9269 |
| language | English |
| last_indexed | 2025-12-07T17:26:43Z |
| publishDate | 2017 |
| publisher | Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| record_format | dspace |
| spelling | Buchynska, L.G. Brieieva, O.V. Lurchenko, N.P. Protsenko, V.V. Nespryadko, S.V. 2018-06-19T09:14:45Z 2018-06-19T09:14:45Z 2017 DNA damage in tumor cells and peripheral blood lymphocytes of endometrial cancer patients assessed by the comet assay / L.G. Buchynska, O.V. Brieieva, N.P. Iurchenko, V.V. Protsenko, S.V. Nespryadko // Experimental Oncology. — 2017 — Т. 39, № 4. — С. 299–303. — Бібліогр.: 35 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/138546 To date, genome instability is considered to be a common feature not only of tumor cells, but also of non-malignant cells of cancer patients, including peripheral blood lymphocytes (PBLs). The issue of the association between genome instability in tumor cells and PBLs, as well as of its relationship with tumor progression remains poorly understood. Aim: To evaluate the level DNA damage in tumor cells and PBLs of endometrial cancer (EC) patients with regard to clinical and morphological characteristics of the patients. Materials and Methods: DNA damage was assessed in 106 PBLs samples and 42 samples of tumor cell suspension from EC patients by comet assay. PBLs from 30 healthy women were used as control. The level of DNA damage was expressed as the percentage of DNA in the comet tails (% tail DNA). Results: It was revealed that the amount of DNA damage in PBLs of EC patients was 2.2 times higher in comparison with that of healthy donors (8.3 ± 0.7 and 3.7 ± 0.4% tail DNA, respectively) (p < 0.05). In this study, no association between the levels of DNA damage in endometrial tumor cells and PBLs was observed (r = 0.11; p > 0.05). The amounts of DNA damage both in tumor cells and PBLs were not related to the degree of tumor differentiation as well as the depth of myometrial invasion, but depended on the body mass index (BMI) of EC patients: high level of lesions was observed in patients with elevated BMI values. Furthermore, the level of DNA damage in tumor cells was associated to familial aggregation of cancer and was significantly higher in endometrial cells from patients with family history of cancer vs that from EC patients with sporadic tumors (32.3 ± 2.9 and 22.8 ± 1.8% tail DNA, respectively) (p < 0.05). It was also found that for women who had high level of DNA damage in PBLs, the risk of EC was greater (odds ratio value of 3.5) compared to those with low level of such lesions. Conclusion: Genome instability that appears as an increased level of DNA damage in tumor cells and PBLs of EC patients is associated with BMI and family history of cancer and can reflect a predisposition to cancer. en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Experimental Oncology Original contributions DNA damage in tumor cells and peripheral blood lymphocytes of endometrial cancer patients assessed by the comet assay Article published earlier |
| spellingShingle | DNA damage in tumor cells and peripheral blood lymphocytes of endometrial cancer patients assessed by the comet assay Buchynska, L.G. Brieieva, O.V. Lurchenko, N.P. Protsenko, V.V. Nespryadko, S.V. Original contributions |
| title | DNA damage in tumor cells and peripheral blood lymphocytes of endometrial cancer patients assessed by the comet assay |
| title_full | DNA damage in tumor cells and peripheral blood lymphocytes of endometrial cancer patients assessed by the comet assay |
| title_fullStr | DNA damage in tumor cells and peripheral blood lymphocytes of endometrial cancer patients assessed by the comet assay |
| title_full_unstemmed | DNA damage in tumor cells and peripheral blood lymphocytes of endometrial cancer patients assessed by the comet assay |
| title_short | DNA damage in tumor cells and peripheral blood lymphocytes of endometrial cancer patients assessed by the comet assay |
| title_sort | dna damage in tumor cells and peripheral blood lymphocytes of endometrial cancer patients assessed by the comet assay |
| topic | Original contributions |
| topic_facet | Original contributions |
| url | https://nasplib.isofts.kiev.ua/handle/123456789/138546 |
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