The study of chromosomal instability in patients with endometrial cancer
Aim: Study is devoted to evaluation of sensitivity of peripheral blood T-lymphocytes (PBL) of patients with endometrial cancer (EC) to genotoxic effect of bleomycin and detection of patients with hidden chromosomal instability. Methods: PBL of 24 EC patients (mean age 58.9 ± 2.9) and 10 healthy wome...
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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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| Назва журналу: | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| Цитувати: | The study of chromosomal instability in patients with endometrial cancer / I.P. Nesina, N.P. Iurchenko, S.V. Nespryad’ko, L.G. Buchynska // Experimental Oncology. — 2014. — Т. 36, № 3. — С. 202-206. — Бібліогр.: 24 назв. — англ. |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine| _version_ | 1860151384358256640 |
|---|---|
| author | Nesina, I.P. Lurchenko, N.P. Nespryadko, S.V. Buchynska, L.G. |
| author_facet | Nesina, I.P. Lurchenko, N.P. Nespryadko, S.V. Buchynska, L.G. |
| citation_txt | The study of chromosomal instability in patients with endometrial cancer / I.P. Nesina, N.P. Iurchenko, S.V. Nespryad’ko, L.G. Buchynska // Experimental Oncology. — 2014. — Т. 36, № 3. — С. 202-206. — Бібліогр.: 24 назв. — англ. |
| collection | DSpace DC |
| container_title | Experimental Oncology |
| description | Aim: Study is devoted to evaluation of sensitivity of peripheral blood T-lymphocytes (PBL) of patients with endometrial cancer (EC) to genotoxic effect of bleomycin and detection of patients with hidden chromosomal instability. Methods: PBL of 24 EC patients (mean age 58.9 ± 2.9) and 10 healthy women-volunteers (mean age 55.7 ± 2.3) were subjected to cytogenetic analysis. Results: Mean spontaneous level of chromosomal aberrations (CA) per 100 analyzed lymphocytes (CA/100) of healthy women has equaled 2.7 ± 0.6, i.e. has not exceeded maximal values of healthy population and was significantly lower (p < 0.05), than in PBL of EC patients (6.9 ± 0.6). After incubation of PBL with bleomycin, number of CA/100 significantly was increased both in control (11.5 ± 1.3) and in EC patients (21.9 ± 1.0). Spontaneous chromosomal instability has been observed in 41.7%, increased sensitivity to bleomycin — in 54.2% and hidden chromosomal instability in 37.5% of patients with EC. It has been shown that level of specific damage of genome in EC patients has constituted 2·10–5, and after exposure with bleomycin, it was increased 4.5 times (9·10–5) that was significantly higher (p < 0.05) compared to control (8·10–6 and 1.0·10–5, respectively). Conclusion: These results have demonstrated that PBL of most patients with EC are characterized by apparent genome alterations, which are manifested by increased number of spontaneous and induced chromosomal damages, hypersensitivity to mutagens and hidden chromosomal instability. Key Words: endometrial cancer, peripheral blood lymphocytes, chromosomal aberrations, hidden chromosomal instability.
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202 Experimental Oncology 36, 202–206, 2014 (September)
THE STUDY OF CHROMOSOMAL INSTABILITY IN PATIENTS
WITH ENDOMETRIAL CANCER
I.P. Nesina1*, N.P. Iurchenko1, S.V. Nespryad’ko2, L.G. Buchynska1
1R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of NAS of Ukraine,
Kyiv 03022, Ukraine
2National Cancer Institute of MH of Ukraine, Kyiv 03022, Ukraine
Aim: Study is devoted to evaluation of sensitivity of peripheral blood T-lymphocytes (PBL) of patients with endometrial cancer (EC)
to genotoxic effect of bleomycin and detection of patients with hidden chromosomal instability. Methods: PBL of 24 EC patients
(mean age 58.9 ± 2.9) and 10 healthy women-volunteers (mean age 55.7 ± 2.3) were subjected to cytogenetic analysis.
Results: Mean spontaneous level of chromosomal aberrations (CA) per 100 analyzed lymphocytes (CA/100) of healthy women has
equaled 2.7 ± 0.6, i.e. has not exceeded maximal values of healthy population and was significantly lower (p < 0.05), than in PBL
of EC patients (6.9 ± 0.6). After incubation of PBL with bleomycin, number of CA/100 significantly was increased both in control
(11.5 ± 1.3) and in EC patients (21.9 ± 1.0). Spontaneous chromosomal instability has been observed in 41.7%, increased sen-
sitivity to bleomycin — in 54.2% and hidden chromosomal instability in 37.5% of patients with EC. It has been shown that level
of specific damage of genome in EC patients has constituted 2·10–5, and after exposure with bleomycin, it was increased 4.5 times
(9·10–5) that was significantly higher (p < 0.05) compared to control (8·10–6 and 1.0·10–5, respectively). Conclusion: These results
have demonstrated that PBL of most patients with EC are characterized by apparent genome alterations, which are manifested
by increased number of spontaneous and induced chromosomal damages, hypersensitivity to mutagens and hidden chromosomal instability.
Key Words: endometrial cancer, peripheral blood lymphocytes, chromosomal aberrations, hidden chromosomal instability.
Searching for genetic markers, which would allow
detecting individuals with predisposition to cancer
and identifying tumor in its initial stages, is urgent
task of modern oncology. Number of reports showed
changes of immune status in cancer patients, inclu-
ding decrease of T-lymphocytes activity due to inhibi-
ting effect of tumor and genetic defects of compo-
nents of immune system [1]. Chromosomal instability
in peripheral blood lymphocytes (PBL) is the evidence
of disorder in genome and, first of all, imperfection
of functioning of DNA reparation genes. It is typical for
many solid tumors, including endometrial cancer (EC),
development of which is connected with mutations
or epigenetically caused changes of genes, which are
responsible for reparation of unpaired bases of DNA —
genes of MMR family and genes-regulators of cell
cycle: PTEN, PIK3, KRAS, BRAF, etc. [2].
According to the results of our previous studies,
increase of mean spontaneous level of chromosomal
aberrations (CA) in PBL of patients with EC com-
pared with healthy women is observed [4]. However,
analysis of individual parameters has determined
patients with low frequency of cells with CA, which
have not exce eded maximal values of healthy popula-
tion (3.0%) [ 4–6]. If we hold the view that individuals
with hidden chromosomal instability exist [7, 8], than
we can assume that patients with EC are divided into
two groups — with existing and hidden chromosomal
instability, which probably plays certain role in patho-
genesis of disease. Increased number of spontane-
ous damages of chromosomes in PBL, hypersensiti-
vity to the impact of mutagenic factors and hidden
chromosomal instability are signs of destabilization
of genome [3, 7–9], study of which becomes more
urgent for detection of individuals susceptible to de-
velopment of malignant tumors, formation of groups
of genetic risk of cancer pathology and further moni-
toring of woman health.
For imitation of impact of hazardous factors on cell
genome, various mutagens are used, among which
most widespread and offered for use in such studies
(in many countries of the world, including Ukraine)
is bleomycin [8, 10, 11]. Mechanism of bleomycin ef-
fect is similar to the effect of many mutagens of physi-
cal and chemical nature (for example, ioni zing radia-
tion or hydrogen peroxide) and is connected with oc-
currence of oxidative stress, in consequence of which
active oxygen forms cause occurrence of single and
double strand breaks of DNA. The highest activity
is performed by bleomycin, when it impacts cells being
in phase G2 of mitotic cycle [8, 10–12].
We designed this study to evaluate the sensitivity
of EC patients’ PBL to genotoxic effect of bleomycin and
detect the patients with hidden chromosome instability.
MATERIALS AND METHODS
PBL were studied from 24 patients with EC in age
from 48 to 67 (mean age 58.9 ± 2.9), which underwent
the treatment at the department of Oncogynecology
at the National Cancer Institute of Ministry of Health
of Ukraine (The head of the Department — M.D.,
Prof. L.I. Vorobyova). Blood from vein was received
from patients before surgical treatment and chemo-
therapy. 10 healthy women-volunteers in the age from
23 to 64 (mean age 55.7 ± 2.3) were included in control
group. All patients have given informed consent for
Submitted: May 20, 2014.
*Correspondence: laboncogen@yandex.ua
Abbreviations used: CA — chromosomal aberrations; EC — endo-
metrial cancer; PBL — peripheral blood T-lymphocytes.
Exp Oncol 2014
36, 3, 202–206
Experimental Oncology 36, 202–206, 2014 (September) 203
blood sampling, cytogenetic studies and use of the re-
sults for research goals.
To study the spontaneous level of CA in PBL of pa-
tients, whole heparinized venous blood (1.0 ml) has been
cultivated during 52 hrs, according to the recommen-
dations [13] with some modifications. For evaluation
of sensitivity of chromosomes to the impact of muta-
gen, PBL of patients with EC and healthy women have
been cultivated during 72 h with adding of bleomycin
hydrochloride solution on 48 hour of cultivation in final
concentration 5 μg/ml [8, 11]. Fixing of specimens and
receiving of metaphase chromosomes has been carried
out by standard method. Staining of specimens has been
performed by Giemsa-trypsin method [13].
Cytogenetic analysis of PBL has been carried out
on codified specimens of chromosomes using of light
microscope at magnification x1250 (oil immersion). Num-
ber of analyzed metaphases varied from 50 to 200 in each
observation. At cytogenetic analysis, number of meta-
phases with CA, number of CA per 100 metaphases
(CA/100) and per 1 aberrant metaphase were calculated.
Also types of CA — chromatid and chromosome bre-
akage were characterized: single acentric fragments and
chromatid-chromatid exchanges, paired acentric frag-
ments, dicentrics, rings, marker chromosomes, breaks
of chromosomes by centromere. Separately localization
of aberrations on chromosome has been determined.
Moreover, for taking into account the number of CA,
which were determined in particular chromosomes
in different groups of karyotype, specific damage-
ability of particular chromosomes (number of points
of damage on group of examined chromosomes) and
specific damageability of genome damage, have been
calculated: (Wі-chromosome) and (Wgenome) [14].
Specific damageability of particular chromosomes
has been calculated by formula:
Wі-chromosome = (n1/N1+....ni/Ni)/LI, (1)
where ni — number of damages in concrete
chromosome in і-patient; Ni — number of analyzed
metaphase plates in і-patient; L — relative length
of chromosome [15]; I — number of patients.
For comparison of level of chromosome damage
in groups of women-volunteers and EC patients, spe-
cific damageability of genome damage by formula has
been determined:
Wgenome = (W1-chromosome +.....+W23-chromosome)/23. (2)
By level of chromosome damage, conclusions
concerning spontaneous and induced instability of ge-
nome and hypersensitivity of chromosomes to the ef-
fect of mutagen have been made, calculating index
mentioned below [11].
Index of spontaneous chromosomal instability (Isci)
has been calculated by formula:
Isci = Msci/M, (3)
where Msci — individual values of spontaneous
frequency of CA, and M — mean group value of sponta-
neous frequency of CA. Index of induced chromosomal
instability (Iici) has been determined by formula:
Iici = Mici/M, (4)
where Mici — individual values of frequency of CA un-
der the effect of bleomycin; M — mean group values
of CA under the effect of bleomycin. Hypersensitive
to bleomycin at that were considered all patients with Iici
higher, than 1.0 (independently from Isci). Patients with
Isci lower than 1.0, and Iici — higher than 1.0 — were
considered to have hidden chromosome instability in PBL.
Statistical analysis of results has been carried out
using Statistica 6.0 (StatSoft, Inc.) with use of non-
parametric criterion of Wilkinson — Mann — Whitney.
Significant were considered diffe rences at р < 0.05.
RESULTS AND DISCUSSION
Spontaneous level of CA/100 in control varied from
1.0 to 4.0 and equaled at the mean to 2.7 ± 0.6, i.e.
has not exceeded mean values in healthy population
(Table 1).
Table 1. Cytogenetic changes in PBL of healthy women and EC patients
Cytogenetic parameters
Control (n = 10) EC patients (n = 24)
Spon-
taneous
level
Induced
level
Spon-
taneous
level
Induced
level
Number of cells with CA, М ± m, % 2.6±0.6 9.3±1.2^ 5.7±0.2* 13.4±0.9*^
Number of CA/100 cells, М ± m
including:
2.7±0.6 11.5±1.3^ 6.9±0.6* 21.9±1.0*^
number of chromatid CA, % 74.1 56.5 62.2 65.8
number of chromosome CA, % 25.9 43.5 37.8 34.2
Number of CA per 1 aber-
rant cell 1.0 1.2 1.2 1.6
Note: *difference between indexes in patients with EC and in control is sig-
nificant (р < 0.05); ̂ difference between indexes of spontaneous and induced
levels of CA is significant (р < 0.05).
In contrast, in PBL of EC patients, spontaneous
level of CA/100 was significantly (р < 0.05) higher, than
in healthy population and in control, and has constituted
6.9 ± 0.6. In all studied specimens, aberrations of chroma-
tid type prevailed and mostly were represented by single
acentric fragments of chromosomes. It should be men-
tioned that individual values of spontaneous frequency
of CA/100 in PBL of patients with EC varied in wider range
(from 2.0–26.0). At that Isci in metaphases of EC patients
varied from 0.3 to 3.8 and in 41.7% of patients was higher,
than 1.0 that is the evidence of presence of spontaneous
chromosome instability in these patients. At the same
time, Isci in control was mostly lower, than 1.0 and only
in one patient it has constituted 1.5.
Undoubtedly important criterion for determination
of cytogenetic changes in cells is evaluation of PBL
sensitivity to mutagenic impact of alkylating substances,
in particular, bleomycin. After incubation of PBL cultures
with bleomycin, frequency of aberrant cells and number
of CA/100 reliably (р < 0.05) increased both in healthy
women and in EC patients. In patients with EC, higher
number of CA/100 (21.9 ± 1.0, at individual variations
from 17.0 to 44.0), than in healthy women (11.5 ± 1.3,
at individual variations 7.0–19.0) was observed. At the
same time, in PBL of healthy women, number of chro-
matid aberrations has decreased and number of aber-
rations associated with damage of chromosomes has
increased. In PBL of patients with EC, after incubation
204 Experimental Oncology 36, 202–206, 2014 (September)
with bleomycin, these indexes have almost not changed
(see Table 1). According to the data of literature [8, 10],
bleomycin is a substance, which, the same as ionizing
irradiation, causes occurrence of aberrations of chro-
mosome type, but presence in analyzed cultures of high
percentage of chromatid aberrations can be the evi-
dence of its action as both radiomimetic and chemical
mutagen.
Besides mentioned above, according to the re-
cent studies, presence in PBL of certain quantity
of CA of chromatid and chromosome types depends
not only on parameters of active substance, but mostly
on polymorphism of series of genes of excisional repa-
ration of DNA bases [16]. In particular, authors showed
that in group of studied children, who lived in the condi-
tions of chronic impact of radon, higher level of aber-
rations of chromatid type in carriers of genotype АРЕ
148Glu/Glu (4.58 ± 0.41; p = 0.045), than in individuals
with genotype APE1 Asp/Asp (3.67 ± 0.33) has been de-
termined. In the same study, decrease of total frequency
of CA in carriers of heterozygote XRCC1 280 Arg/His
of genotype (4.55 ± 0.57; p = 0.04) compared with
Arg/Arg genotype (5.59 ± 0.22) has been determined.
In our opinion, detected high level of spontaneous
and hidden chromosomal instability in patients with
EC is also result of disorder of functioning of systems
of DNA reparation that can be one of the reasons
of development in these patients of cancer disease.
This assumption can be confirmed by the study
of effectiveness of DNA reparation (method of ge l-e-
lectrophoresis of isolated cells), which has been previ-
ously performed by us in this group of patients. It has
been determined that after processes of reparation
in PBL of EC patients, 63.9 ± 20.9% of DNA damages
(in control — 80.2 ± 3.0%) have been repaired [17].
Analysis of PBL genome destabilization under
the effect of bleomycin, which was evaluated by corre-
sponding coefficients, has determined that increased
sensitivity to bleomycin is observed in 54.2% of pa-
tients with EC (Iici > 1.0, at individual variations of Iici
from 1.2 to 2.4) and hidden chromosome instability
has been detected in 37.5% of cases (at Isci < 1.0, Iici
> 1.0) (Table 2, Fig. 1).
Table 2. Distribution of patients by rates of spontaneous chromosomal in-
stability in PBL
Groups
of patients
Number of patients, %
Isci Iici Isci
<1.0
Iici
<1.0
Isci
>1.0
Iici
<1.0
Isci >1.0
Iici >1.0
Isci <1.0
Iici >1.0<1.0 >1.0 <1.0 >1.0
Control,
n=10/100%
90.0 10.0 80.0 20.0 80.0 − 10.0 10.0
EC patients,
n=24/100%
58.3 41.7 45.8 54.2 20.8 25.0 16.7 37.5
In contrast, only two women (20.0%) in control had
increased sensitivity to bleomycin and one (10.0%) —
hidden chromosome instability.
One more parameter, which shows chromosome
instability, is presence of multi-aberrant cells being
determined by number of CA per 1 aberrant cell. Be-
fore bleomycin impact, metaphases with two or more
CA were determined in PBL of 33.3% of patients with
EC, and after incubation of PBL with bleomycin —
in 100.0% of EC patients. Due to this, after bleomycin
effect, in PBL of all patients with EC, number of CA in-
creased as well as index of quantity of CA per 1 aber-
rant cell (at the mean up to 1.6) that was higher, than
its values in control (1.2). Moreover, in PBL, after
incubation with bleomycin, wide range of aberration
forms has been observed — dicentric chromosomes,
chromatid-chromatid exchanges arose (Fig. 2).
0 10 20 30 40 50 60
Spontaneous chromo-
somal instability
Increased sensitivity
to bleomycin
Hidden chromo-
somal instability
Number of cases, %
Control
EC patients
Fig. 1. Distribution of examined women (%) with spontaneous
and hidden chromosome instability and increased sensitivity
of chromosomes to the impact of bleomycin in PBL
a b c
Fig. 2. Fragments of metaphase plates with chromosome aber-
rations in PBL of EC patients after bleomycin impact: a) chroma-
tid-chromatid exchange and single acentric fragment; b) single
and paired acentric fragments; c) dicentric chromosome with
paired acentric fragment. Giemsa staining, ×1250 (oil immersion)
When carrying out study, we paid attention to the pre-
sence of “marker” chromosome in PBL of one patient
(K., 61 years), with family history of cancer: brother —
colorectal cancer, grandfather by mother’s side — pros-
tate cancer. After incubation with bleomycin, at ana lysis
of 143 metaphases of this patient, large acrocentric
“marker” chromosome, which was found with frequency
2.1 per 100 cells, has been detected.
Though bleomycin is not referred to mutagens
used for detection of chromosomal fragile sites (FS),
but it is logically to suppose that after impact of this
mutagen, CA occur, first of all, exactly in these parts
of chromosomes.
At karyotype analysis, which was carried out
at G-staining of metaphase chromosomes, we have
determined in PBL of healthy women one FS, which
has been detected on chromosome 2p15, but in the list
of FS in this part no FS was registered [18]. At the same
time, in PBL of two patients with EC, up before impact
of bleomycin, nonrandom sites of chromosome da-
mage (in one patient in part 2p23, in second — 12q24)
have been determined. After incubation with bleomy-
cin, in PBL of 40.0% of EC patients, increased fragility
of chromosomes in certain sites, which by localization
Experimental Oncology 36, 202–206, 2014 (September) 205
coincide with known FS of chromosomes 1, 2, 4, 5, 8,
12 and 17: 1p32 (FRA1B); 1p36 (FRA1A); 1q31 (FRA1K);
2p13 (FRA2B); 2q22–31 (FRA2F, FRA2G); 2qter
(FRA2J); 4q31 (FRA4C); 5q13–15 (FRA5A, FRA5B);
5q31 (FRA5C); 8q24 (FRA8C, FRA8D, FRA8E);
12q13 (FRA12A) and 17р12-(FRA17A), has been
determined [18]. Moreover, identification of genes
in FS of chromosomes according to the NGNC da-
tabase, allowed us to determine that in these sites
exactly or besides them, key genes of reparation and
regulation of cellular cycle (1р3.2 — BLYM, MYCLI,
TALI, JUN; 1q2.2–2.4 — SKI, 1q23-q31-TRKB, TRKC;
2q3.3-qter — INHA; 4q3.1 — IL15; 5q2.1- q2.2 — АРС,
5q2.1- q3.1 — СTNN1, etc.) are located. We should
pay attention on determined damages of chromo-
some 12 in site 12p11-p13 — exactly in this part are
located genes, which are connected with development
(12p12.1 — KRAS2) and progression (12-q24.13 —
C-MYC, 12p11-р14 — TFRβ, 12p13 — CDК2, CDК4)
of EC [19–22].
Obtained results of cytogenetic analysis can
be the evidence of nonrandom nature of localization
of chromosomal damages in PBL of patients with
EC. Obtained results in certain measure coincide with
results of other researchers, who have noticed four
regions in chromosomes in PBL of patients with EC,
in which FS were mostly found (1q2.4–3.1; 2q2.4–3.1;
4q2.5–3.1; 5q2.3–3.2) [23].
Results of calculation of spontaneous and induced
specific damageability of chromosomes from diffe-
rent karyotype groups in PBL of healthy women and
EC patients are represented in Fig 3.
0
0,00005
0,0001
0,00015
0,0002
0,00025
0,0003
0,00035
A B C D E F G A B C D E F G
Control EC patients
Sp
ec
ifi
c
da
m
ag
ea
bi
lit
y
of
c
hr
om
os
om
es Spontaneous level
Induced level
Groups
of chromosomes
Fig. 3. Comparison of spontaneous and bleomycin-induced
specific damageability of chromosome damage of different
karyotype groups in healthy women and in EC patients
Analysis of spontaneous frequency of CA in PBL
of patients with EC has showed that the highest number
of susceptible sites has been detected in chromosomes
from groups E, C and A and in a smaller number —
in groups B and D, and aberrations of chromosomes were
not observed in groups F and G. In control, chromosomes
of different groups have been damaged with almost equal
frequency, except groups D and G, in which aberrations
of chromosomes were not observed.
After bleomycin impact, specific damageability
of chromosome has increased both in PBL of healthy
women and in patients with EC. This damageability was
significantly (р < 0.05) higher in groups A, B, C, E and,
at the same time, induced damages in chromosomes
from group F occurred. In general, in PBL of healthy
individuals, specific damageability of chromosome af-
ter incubation of them with bleomycin was significantly
(р < 0.05) lower, than in patients with EC and damages
have been mostly observed in chromosomes of groups
A and B.
At calculation of specific damageability of ge-
nome (Wgenome) of PBL, it has been determined that
in patients with EC, spontaneous level of Wgenome has
equaled 2•10–5, and after impact of bleomycin it has
significantly (р < 0.05) increased in 4.5 times and has
constituted 9•10–5. In PBL of healthy women, Wgenome
has equaled 8•10–6, and after incubation with bleo-
mycin, it has increased only up to 1.0•10–5 (Table 3).
Table 3. Indexes of specific weight of chromosome damage (Wgenome)
in PBL of healthy donors and patients with EC
Group of patients Level of Wgenome
Spontaneous Bleomycin-induced
Control 8.0•10–6 1.0•10–5
EC patients 2.0•10–5* 9.0•10–5*
Note: *difference between indexes of EC patients and in control is signifi-
cant (р < 0.05).
Thus, results of cytogenetic study allowed us to de-
tect series of differences between indexes of chromo-
some instability in PBL of healthy women and in pa-
tients with EC, main of which is high sensitivity of PBL
of EC patients to mutagenic action of bleomycin. It should
be mentioned that during carrying out of antitumor treat-
ment (radio- and chemotherapy), detected high specific
damageability of chromosome in patients with EC can
cause progressive increase of genome destabilization
and occurrence of secondary tumors.
It can be assumed that hypersensitivity of chromo-
somes of PBL of patients with EC to the effect of bleomy-
cin is not sporadic, but is conditioned by hereditary fac-
tors. This assumption can be confirmed by data of other
authors, who have showed that sensitivity of PBL to the
effect of mutagens is genetically determined. In particu-
lar, differences in sensitivity of chromosomes to bleo-
mycin of PBL of mono- and dizygotic twins have been
determined [24]. Moreover, it has been demonstrated
in series of studies that increased sensitivity of PBL
to the effect of genotoxic agents is indicator of genetic
predisposition of such individuals to cancer [7, 16, 24].
At the same time, it is known that at simultaneous impact
of radioactive and chemical factors on organism (envi-
ronment of the most populations in urbanized countries),
they are able to perform both additive and multiplicative
effect, and peculiarities of cumulative action of genetic
and environmental factors is increase of multiplicative
effect [9]. Since exactly genetic mechanisms determine
differences in people’s reactions to the impact of harmful
factors, it can be assumed that presence of genetically
determined genome instability is one of the key reasons
of EC, which has been realized in the harmful conditions
of environment. Thus, determination of spontaneous and
bleomycin-induced level of CA in PBL helps us to detect
individuals with high level of genome destabilization
and high sensitivity to genotoxic environmental factors.
It indicates the necessity of carrying out cytogenetic
206 Experimental Oncology 36, 202–206, 2014 (September)
examination in EC patients, and, on the condition of he-
reditary nature of disease, also in their female relatives
with the aim to detect individuals with high risk of cancer
among them.
Therefore, our findings indicate that PBL of most
patients with EC are characterized by apparent genome
destabilization, which has individual peculiarities and
is manifested by increased number of spontaneous and
induced damages of chromosomes, hypersensitivity
to the impact of mutagenic factors and hidden chromo-
somal instability. Sites of high fragility, which were de-
tected in chromosomes of PBL of EC patients, by their
localization coincide with known FS of chromosomes,
arrangement of some genes-suppressors, proto- and
oncogenes, including genes involved in malignant
transformation of endometrial cells, and with some sites
of chromosomal damages, which are detected in tumor
cells of endometrium. Cytogenetic study of PBL has
clinical significance for detection of individual indica-
tors being genetic markers of genome instability that
must be taken into account while carrying out antitumor
treatment of patients.
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Copyright © Experimental Oncology, 2014
|
| id | nasplib_isofts_kiev_ua-123456789-145367 |
| institution | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| issn | 1812-9269 |
| language | English |
| last_indexed | 2025-12-07T17:51:53Z |
| publishDate | 2014 |
| publisher | Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| record_format | dspace |
| spelling | Nesina, I.P. Lurchenko, N.P. Nespryadko, S.V. Buchynska, L.G. 2019-01-21T08:18:06Z 2019-01-21T08:18:06Z 2014 The study of chromosomal instability in patients with endometrial cancer / I.P. Nesina, N.P. Iurchenko, S.V. Nespryad’ko, L.G. Buchynska // Experimental Oncology. — 2014. — Т. 36, № 3. — С. 202-206. — Бібліогр.: 24 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/145367 Aim: Study is devoted to evaluation of sensitivity of peripheral blood T-lymphocytes (PBL) of patients with endometrial cancer (EC) to genotoxic effect of bleomycin and detection of patients with hidden chromosomal instability. Methods: PBL of 24 EC patients (mean age 58.9 ± 2.9) and 10 healthy women-volunteers (mean age 55.7 ± 2.3) were subjected to cytogenetic analysis. Results: Mean spontaneous level of chromosomal aberrations (CA) per 100 analyzed lymphocytes (CA/100) of healthy women has equaled 2.7 ± 0.6, i.e. has not exceeded maximal values of healthy population and was significantly lower (p < 0.05), than in PBL of EC patients (6.9 ± 0.6). After incubation of PBL with bleomycin, number of CA/100 significantly was increased both in control (11.5 ± 1.3) and in EC patients (21.9 ± 1.0). Spontaneous chromosomal instability has been observed in 41.7%, increased sensitivity to bleomycin — in 54.2% and hidden chromosomal instability in 37.5% of patients with EC. It has been shown that level of specific damage of genome in EC patients has constituted 2·10–5, and after exposure with bleomycin, it was increased 4.5 times (9·10–5) that was significantly higher (p < 0.05) compared to control (8·10–6 and 1.0·10–5, respectively). Conclusion: These results have demonstrated that PBL of most patients with EC are characterized by apparent genome alterations, which are manifested by increased number of spontaneous and induced chromosomal damages, hypersensitivity to mutagens and hidden chromosomal instability. Key Words: endometrial cancer, peripheral blood lymphocytes, chromosomal aberrations, hidden chromosomal instability. en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Experimental Oncology Original contributions The study of chromosomal instability in patients with endometrial cancer Article published earlier |
| spellingShingle | The study of chromosomal instability in patients with endometrial cancer Nesina, I.P. Lurchenko, N.P. Nespryadko, S.V. Buchynska, L.G. Original contributions |
| title | The study of chromosomal instability in patients with endometrial cancer |
| title_full | The study of chromosomal instability in patients with endometrial cancer |
| title_fullStr | The study of chromosomal instability in patients with endometrial cancer |
| title_full_unstemmed | The study of chromosomal instability in patients with endometrial cancer |
| title_short | The study of chromosomal instability in patients with endometrial cancer |
| title_sort | study of chromosomal instability in patients with endometrial cancer |
| topic | Original contributions |
| topic_facet | Original contributions |
| url | https://nasplib.isofts.kiev.ua/handle/123456789/145367 |
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