Analysis of relative telomere length and apoptosis in humans exposed to ionising radiation
Background: Ionizing radiation could modify lymphocyte function via oxidative damage, DNA breaks, and resulting changes of proliferation, apoptosis and cellular senescence, where telomeres may play a critical role. Aim: To study the effect of low-dose irradiation on the telomere length and apoptosis...
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irk-123456789-1386802018-06-20T03:10:46Z Analysis of relative telomere length and apoptosis in humans exposed to ionising radiation Ilyenko, I. Lyaskivska, O. Bazyka, D. Original contributions Background: Ionizing radiation could modify lymphocyte function via oxidative damage, DNA breaks, and resulting changes of proliferation, apoptosis and cellular senescence, where telomeres may play a critical role. Aim: To study the effect of low-dose irradiation on the telomere length and apoptosis rates in peripheral blood lymphocytes of irradiated persons. Patients and Methods: A study was performed on 83 peripheral blood samples from the Chornobyl clean-up workers, radiation workers exposed under the professional limits at construction works at the “Shelter” object and healthy controls. Bone marrow leukocyte telomere length was estimated in 15 patients with myelodysplastic syndrome secondary to low-dose radiation exposure and 12 age-standardized healthy donors. Relative telomere length was studied by the combination of a fluorescence hybridization in situ with PNA probe and flow cytometry, apoptosis — by Annexin-V test. Results: A significant relative telomere length decrease has been demonstrated in Chornobyl clean-up workers compared to healthy donors (13.2 ± 0.69 and 18.6 ± 0.73 respectively, p < 0.05), and a tendency (p < 0.1) in radiation workers. At doses over professional limits an inverse dependency is demonstrated between the relative telomere length and a number of lymphocytes in early stage of apoptosis. In MDS group a tendency of telomere elongation was demonstrated in bone marrow granulocytes in RAEB-t and RAEB as comparing with RA. Conclusion: This study shows telomere shortening after low-dose irradiation and preservation of these changes even 20 years after exposure. Apoptosis induction is possible by the telomere region changes at least in individuals with shorter telomeres. Apoptosis decrease in MDS clonal transformation is associated with a substantially longer telomeres. 2011 Article Analysis of relative telomere length and apoptosis in humans exposed to ionising radiation / I. Ilyenko, O. Lyaskivska, D. Bazyka // Experimental Oncology. — 2011. — Т. 33, № 4. — С. 235-238. — Бібліогр.: 19 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/138680 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Original contributions Original contributions |
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Original contributions Original contributions Ilyenko, I. Lyaskivska, O. Bazyka, D. Analysis of relative telomere length and apoptosis in humans exposed to ionising radiation Experimental Oncology |
| description |
Background: Ionizing radiation could modify lymphocyte function via oxidative damage, DNA breaks, and resulting changes of proliferation, apoptosis and cellular senescence, where telomeres may play a critical role. Aim: To study the effect of low-dose irradiation on the telomere length and apoptosis rates in peripheral blood lymphocytes of irradiated persons. Patients and Methods: A study was performed on 83 peripheral blood samples from the Chornobyl clean-up workers, radiation workers exposed under the professional limits at construction works at the “Shelter” object and healthy controls. Bone marrow leukocyte telomere length was estimated in 15 patients with myelodysplastic syndrome secondary to low-dose radiation exposure and 12 age-standardized healthy donors. Relative telomere length was studied by the combination of a fluorescence hybridization in situ with PNA probe and flow cytometry, apoptosis — by Annexin-V test. Results: A significant relative telomere length decrease has been demonstrated in Chornobyl clean-up workers compared to healthy donors (13.2 ± 0.69 and 18.6 ± 0.73 respectively, p < 0.05), and a tendency (p < 0.1) in radiation workers. At doses over professional limits an inverse dependency is demonstrated between the relative telomere length and a number of lymphocytes in early stage of apoptosis. In MDS group a tendency of telomere elongation was demonstrated in bone marrow granulocytes in RAEB-t and RAEB as comparing with RA. Conclusion: This study shows telomere shortening after low-dose irradiation and preservation of these changes even 20 years after exposure. Apoptosis induction is possible by the telomere region changes at least in individuals with shorter telomeres. Apoptosis decrease in MDS clonal transformation is associated with a substantially longer telomeres. |
| format |
Article |
| author |
Ilyenko, I. Lyaskivska, O. Bazyka, D. |
| author_facet |
Ilyenko, I. Lyaskivska, O. Bazyka, D. |
| author_sort |
Ilyenko, I. |
| title |
Analysis of relative telomere length and apoptosis in humans exposed to ionising radiation |
| title_short |
Analysis of relative telomere length and apoptosis in humans exposed to ionising radiation |
| title_full |
Analysis of relative telomere length and apoptosis in humans exposed to ionising radiation |
| title_fullStr |
Analysis of relative telomere length and apoptosis in humans exposed to ionising radiation |
| title_full_unstemmed |
Analysis of relative telomere length and apoptosis in humans exposed to ionising radiation |
| title_sort |
analysis of relative telomere length and apoptosis in humans exposed to ionising radiation |
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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2011 |
| topic_facet |
Original contributions |
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http://dspace.nbuv.gov.ua/handle/123456789/138680 |
| citation_txt |
Analysis of relative telomere length and apoptosis in humans exposed to ionising radiation / I. Ilyenko, O. Lyaskivska, D. Bazyka // Experimental Oncology. — 2011. — Т. 33, № 4. — С. 235-238. — Бібліогр.: 19 назв. — англ. |
| series |
Experimental Oncology |
| work_keys_str_mv |
AT ilyenkoi analysisofrelativetelomerelengthandapoptosisinhumansexposedtoionisingradiation AT lyaskivskao analysisofrelativetelomerelengthandapoptosisinhumansexposedtoionisingradiation AT bazykad analysisofrelativetelomerelengthandapoptosisinhumansexposedtoionisingradiation |
| first_indexed |
2025-07-10T06:21:10Z |
| last_indexed |
2025-07-10T06:21:10Z |
| _version_ |
1837239868589080576 |
| fulltext |
Experimental Oncology ��� �������� ���� ��ecem�er���� �������� ���� ��ecem�er� ��ecem�er� ���
ANALYSIS OF RELATIVE TELOMERE LENGTH AND APOPTOSIS
IN HUMANS EXPOSED TO IONISING RADIATION
I. Ilyenko, O. Lyaskivska, D. Bazyka*
Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine, Kyiv 04050,
Ukraine
Background: Ionizing radiation could modify lymphocyte function via oxidative damage, DNA breaks, and resulting changes of pro-
liferation, apoptosis and cellular senescence, where telomeres may play a critical role. Aim: To study the effect of low-dose irradiation
on the telomere length and apoptosis rates in peripheral blood lymphocytes of irradiated persons. Patients and Methods: A study was
performed on 83 peripheral blood samples from the Chornobyl clean-up workers, radiation workers exposed under the professional limits
at construction works at the “Shelter” object and healthy controls. Bone marrow leukocyte telomere length was estimated in 15 patients
with myelodysplastic syndrome secondary to low-dose radiation exposure and 12 age-standardized healthy donors. Relative telomere
length was studied by the combination of a fluorescence hybridization in situ with PNA probe and flow cytometry, apoptosis — by An-
nexin-V test. Results: A significant relative telomere length decrease has been demonstrated in Chornobyl clean-up workers compared
to healthy donors (13.2 ± 0.69 and 18.6 ± 0.73 respectively, p < 0.05), and a tendency (p < 0.1) in radiation workers. At doses over
professional limits an inverse dependency is demonstrated between the relative telomere length and a number of lymphocytes in early
stage of apoptosis. In MDS group a tendency of telomere elongation was demonstrated in bone marrow granulocytes in RAEB-t and
RAEB as comparing with RA. Conclusion: This study shows telomere shortening after low-dose irradiation and preservation of these
changes even 20 years after exposure. Apoptosis induction is possible by the telomere region changes at least in individuals with shorter
telomeres. Apoptosis decrease in MDS clonal transformation is associated with a substantially longer telomeres.
Key Words: radiation, telomere, apoptosis, Chernobyl, myelodysplastic syndrome.
The critical function of telomeres consists in adjust-
ing the cellular response to stress and growth stimula-
tion �ased on previous cell divisions and occurs via
progressive reduction of telomere length and respec-
tive �NA damage that is activated �y terminal chromo-
some regions not containing telomere sequences [�].
Low-dose ionizing radiation is regarded as one of fac-
tors that finally affect life-span via modification of cell
functioning through the mechanisms of oxidative
stress� �NA damage� cellular senescence� apoptosis
and compensatory proliferation [�]. These factors are
�elieved to play a role in genome insta�ility and form
a �ackground for radiation-dependent aging. Also
telomere shortening may serve as a surrogate marker
of tumor progression and seems to �e accelerated
in allogenic �one marrow transplant recipients [�].
In radiation �iology this question is not clearly under-
stood. Neuhof et al. [4] suggest telomerase activity
to �e the radiation modified function� responsi�le for
the damage �NA. Length of telomeres is also associ-
ated with enhanced chromosome radiosensitivity that
is demonstrated in murine acute myeloid leukemia cell
line 79�6 [4� �]. In radiosensitive cells short telomeres
might correlate with radiation sensitivity [6]. Such
conclusion could �e applied to such radiosensitive
cells as human lymphocytes and other types of leuko-
cytes. Some other data show that long telomeres� �ut
not telomerase activity seem �e factor protecting
proliferation activity under radiation exposure [�� 7].
Appearance of radiation senescence in people who
suffered due to Chorno�yl accident� is among the most
de�ata�le aspects of �iological effects of irradiation.
In some pu�lications the phenomenon of such se-
nescence has �een registered in population that lives
on radionuclide-contaminated territories� and this phe-
nomenon is �elieved to �e associated with altered im-
mune functions� lymphoadenopathy and lymphopenia�
increased incidence of autoimmune thyroiditis and other
allergic diseases [�]. Individuals who suffered as a result
of the Chorno�yl accident� might have genome changes�
changes in lineage-associated or functionally active
�iomolecules� such as lack of C��� on C��+ cells� that
are experimentally shown to result in lower proliferative
activity� decreased IL-� production� telomere erosion
and lesser response to TCR stimulation [9]. It is impor-
tant to reveal the mechanisms involved in the radiation
induced senescence� including the telomere shortening
and apoptosis. �ue to the emerging data on cell senes-
cence as questiona�le radiation effect in human �ody�
it is especially important to o�tain compara�le results
using the quantitative approach.
MATERIALS AND METHODS
In total ��� individuals were enrolled to a study: �� con-
trol group was composed from �� healthy individuals with
normal within the age limits haematological and immuno-
logical indices; �� the group of irradiated individuals �n =
7�� included a� �� clean-up workers of �9�6��9�7 at the
late period after radiation exposure of ��6 ± 9� �M ± m�
mSv; �� �� acute radiation syndrome �ARS� survivors
after a high dose radiation exposure of �4�� ± ��� �M
± m� mSv� and c� �� radiation workers exposed under
Received: August 2, 2011.
*Correspondence: Fax: +38044 4092955
E-mail: bazyka@yahoo.com
Abbreviations used: ARS — acute radiation syndrome; FISH — fluo-
rescence in situ hybridization; MDS — myelodysplastic syndrome;
PBL — peripheral bloody lymphocytes; PNA — peptide nucleic.
acid; RTL — relative telomere length;
Exp Oncol ����
��� 4� �������
��6 Experimental Oncology ��� �������� ���� ��ecem�er�
the professional limits during construction works at the
“Shelter” o�ject with the dose of external irradiation
of �� ± �.�7 �M ± m� mSv; �� special comparison group
included �� patients with myelodysplastic syndrome
�M�S� that has developed in � to �� years after low-
dose radiation exposure during the Chorno�yl accident.
Mean age of su�jects included to control group was
��.�±�.�4 �M ± m� years� clean-up workers — �6.� ±
�.�9 years� ARS survivors — 6�.� ± �.�6 years� radiation
workers — 47.4 ± �.4� years. All persons enrolled into the
study have given an informed written consent.
Study of the relative telomere length �RTL� was
conducted in peripheral �lood lymphocytes �y the
flow-FISH assay� that com�ines the fluorescent hy�rid-
ization in situ and flow cytometry with a Telomere PNA
Kit/FITC ��ako Cytomation� �enmark� using a FITC�
conjugated peptide nucleic acid �PNA� pro�e. This
kit is recommended for RTL evaluation in nucleated
haematopoietic cells. K�6� cells with known telomere
length were used as control. Cell line was o�tained
from the Bank of Cell Lines from Human and Animal
Tissues� R.E. Kavetsky Institute of Experimental Pa-
thology� Oncology and Radio�iology of NAS of Ukraine.
Sample peripheral �lood leukocytes were mixed
with control cells and distri�uted to two microcentifuge
tu�es. The sample �NA was denatured during �� min.
at �� °C. Hy�ridization solution without pro�e was inject-
ed to a control tu�e� and hy�ridization solution with flu-
orescein-conjugated PNA telomere pro�e to a sample
tu�e. Hy�ridization was performed in the dark at room
temperature overnight. The hy�ridization was followed
�y two ��-min post-hy�ridization washes with a Wash
Solution at 4� °C. Pellets in the sample and control tu�es
were resuspended for further flow cytometric analysis.
Samples hy�ridized with the Telomere PNA Pro�e/FITC
exhi�it fluorescence signal in FL�� which is higher than
the �ackground/autofluorescence signal o�tained
from the control of the same cells hy�ridized with the
hy�ridization solution without pro�e. Cell gating for flow
cytometry included cells in G�-G�-phases and gated
cells were displayed for analysis in the FL�-height ver-
sus FL�-height dot plot. Standard three part differential
gating was used for separate analysis of lymphocytes
and granulocytes. The RTL value is calculated as the
ratio �etween the telomere signal of each sample and
the control cell �K�6� cell line� with correction for the
�NA index of G�/� cells �y a formula:
(mean FL1exp.cells with PNA) — (mean FL1exp. cells without PNA)RTL = ———————————————————————————————————————————————— × 100
(mean FL1ctrl cells with PNA) — (mean FL1ctrl cells without PNA)
The differential analysis of apoptosis rate was con-
ducted �y the Annexin V-FITC Apoptosis �etection Kit
I �B�� USA� �y flow cytometry analysis with the use
of standard protocol. Shortly� the cells �~� x ��6 cells/ml�
were twice washed with cold PBS and then in �X Bind-
ing Buffer ��.� M Hepes/NaOH �pH 7.4� �.4 M NaCl�
�� mM CaCl��� mixed with � µl Annexin V and � µl PI�
incu�ated for �� min at RT in the dark� and analyzed
�y flow cytometry on a FACScan �B�� USA�. Batch
analysis of flow cytometry data was performed in Lysis
II and WINM�I �.� software� statistical analysis of the
results was conducted using SPSS �6.�. package.
RESULTS
The performed study has shown a decrease of the
mean RTL values of PBL in all groups of radiation exposed
individuals �Fig. ��. The most significant decrease was
typical for a group of Chorno�yl cleanup workers� while
in the group of radiation workers differences with control
values were less significant. In ARS survivors we have
found an increased heterogeneity of RTL values.
28
24
20
16
12
8
4
RT
L
0 1 2 3 4
Regression
95% confid.
Fig. 1. RTL distri�ution plot in different groups of patients: � —
ARS; � — Chorno�yl clean-up workers; � — radiation workers;
4 — control group; Y-axis — RTL �%�
We have studied telomere length in leukocytes from
�� patients with myelodysplastic syndrome �M�S� that
was developed after exposure to Chorno�yl low-dose
radiation. Bone marrow cells were o�tained from 7 refrac-
tery anemia �M�S-RA� patients� 6 refractery anemia with
excess of �lasts �M�S-RAEB� and � refractery anemia with
excess of �lasts in transformation to leukemia �RAEB-t� pa-
tients and �� age-matched healthy volunteers. The mean
RTL values were higher in M�S-RAEB/RAEB-t patients
as compared with M�S-RA ���.��±�.�� vs �4.�6±�.7��.
Significant difference in mean RTL values �etween RAEB-
t and control groups was demonstrated �Fig. ��. M�S-
RA samples were characterized �y high level of apoptosis
in granulocytes and lymphocytes and significantly lower
RTL index in comparison with that in healthy controls.
Comparison of M�S-RA group with other groups of irra-
diated individuals has shown the a�sence of differences
in spontaneous level of lymphocyte early apoptosis while
the late apoptotic cell fraction �AnnexinV+PI+ cells� was
significantly larger in RA group. with No difference
in apoptosis was shown �etween exposed and non-
exposed M�S-RA su�groups. Mean RTL indices in the
radiation-exposed RA su�group were lower in comparison
with other groups except the cleanup workers group.
Correlation was found �etween age and num�er of cells
in early apoptosis� �ut not �etween age and RTL. RAEB-
t cases have shown a pronounced decrease in the num�er
of cells at all apoptosis stages. These results point on pos-
si�le relationship �etween apoptosis induction and the
telomere region changes in M�S. RA is associated with
cell entry to the late apoptosis stage.
To study radiation-induced early changes of periph-
eral �lood lymphocytes telomere length we have con-
ducted the RTL study in “Shelter” staff exposed to a low
Experimental Oncology ��� �������� ���� ��ecem�er���� �������� ���� ��ecem�er� ��ecem�er� ��7
dose exposure during the shift works in ��-km exclusion
zone and found a significant inverse correlation �etween
the RTL and a radiation dose �Pearson r = -��669�
p < �.�49�. The highest num�ers of annexinV+PI- cells
in early apoptosis stage and annexinV+PI+ cells in late
apoptosis stage have �een detected in the group
of Chorno�yl clean-up workers �Fig. �� Fig. 4�.
0
5
10
15
20
25
30
Control RA RAEB RAEB-t
RT
L
Fig. 2. Mean RTL indices in M�S group
Annexin + PI-, %
0
25
50
75
A
Control Object of «Shelter» Clean-up workers
Fig. 3. Num�er of lymphocytes �%� in early stage of apoptosis
in different groups of patients
Annexin + PI+, %
0
10
20
30
Control Object of «Shelter» Clean-up workers
Fig. 4. Num�er of lymphocytes �%� at late stage of apoptosis
in different groups of patients
The data on the relationship �etween the RTL va-
lues and apoptosis rate in PBL are presented in Fig. 4.
The groups of persons with higher doses of irradiation
are characterized �y the declined RTL. For annexin+PI-
fraction� however these changes are of an opposite
type. The lower RTL values are associated with the
higher apoptosis levels� especially nota�le in a group
of clean-up workers �Fig. ��. Such type of response
with a reduction of telomere length together with oxida-
tive cell damage and genome insta�ility might result
in elimination of defective cell �y apoptosis.
50
40
30
20
10
0
%
RTL
Annexin + PI-, %
RTL
Annexin + PI-, %
Control Object of «Shelter» Clean-up workers
Fig. 5. �ependence �etween the RTL values and num�er of cells
in apoptosis in different groups of patients
DISCUSSION
According to literature data� some dualism exists �e-
tween telomere length and cancer development. Longer
telomeres are associated with an extensive tumor growth
and poor prognosis [��� ��]. A question appear� is it pos-
si�le to consider such process as an increased replication
senescence� or radiation-induced cellular senescence?
In previous studies telomeres in a group of ��� individu-
als were associated with in vitro radiosensitivity as the
group with short telomeres presented higher frequencies
of ionizing radiation-induced micronuclei when compared
to the long telomeres group and the individual telomere
length is regarded as �iomarker of individual chromo-
some insta�ility upon exposure to ionizing radiation
[��]. Later study hasn’t shown differences in cell cycle
regulatory proteins �cyclins A� B�� ��� E� and Ki67� and
telomere length in radiation-induced and sporadic papil-
lary thyroid carcinoma. Coming from the theory of cellular
senescence� which is �ound to reduction of telomere
ends of chromosomes and our findings� the two ways
of realization of cellular cycle could �e pro�a�le: cells can
�e eliminated �y apoptosis� or move to a “senile” pheno-
type. The last type could �e of some positive importance�
as far as cellular senescence decreases the proliferation
rates and thus �locks carcinogenesis [��� �4]. Vice versa�
an accumulation of genetic errors at senescence could
also lead to cell transformation. The other way is a pro-
grammed cellular death. Realization of apoptosis includes
a cascade of reactions� in which one of main roles is played
�y TP53 gene and its product — р��. However� in cells
with p�� mutations genome insta�ility is increased� which
promotes malignant transformation. Malignant cells over-
express telomerase that elongates telomeres and allows
for plentiful divisions. Telomere elongation is a common
molecular feature of advanced malignancies� �ut there
is some evidence suggesting that short telomeres and
concurrent chromosomal insta�ility contri�ute to malig-
nant cell transformation [��� ��].
Our data on M�S are in consistence with work
of P. Schein�erg et al. [�6]. In a cohort of ��� patients
with severe aplastic anemia receiving immunosuppres-
sive therapy� telomere length was unrelated to response
�ut was associated with risk of relapse� clonal evolu-
tion to myelodysplasia� and overall survival. Authors
suggest that telomere assessment may �e of potential
��� Experimental Oncology ��� �������� ���� ��ecem�er�
diagnostic value in myeloprolipherative disease. In our
study none of remarka�le differences in telomere
length have �een demonstrated �etween M�S-RA and
age-standardized controls. Specific diagnostic value
of RTL seems disputa�le. In tumor pathology the low
leukocyte telomere length with the associated cell
su�set changes seem to �e a sign of a decreased
anti-tumor surveillance as a factor promoting clonal
growth. Therefore� low RTL values in clean-up workers
peripheral �lood lymphocytes possi�ly display a genetic
insta�ility in a late period after irradiation� as well as the
development of cellular aging and potential suscepti�il-
ity to oncologic transformation. There are suggestions
that telomere shortening might �e the main or even the
sole mechanism of the natural and radiation aging [�7].
Our study shows that there is a su�stantial change
in telomere length as in the early and also in the late
period after radiation exposure and these changes are
related to changes of apoptosis rates. This suggestion
is confirmed �y other studies using the advances in the
molecular pathology of hematopoietic stem cells which
indicate that there exist a fine �alance �etween various
extrinsic and intrinsic signaling pathways in preserving
the self-renewal and proliferative capacity of stem cells.
Extrinsic signaling involves a microenvironment niche fac-
tors such as neigh�oring stromal cells� osteo�lasts� and
adipocytes secreting cytokines� chemokines� and metal-
loproteinases; intrinsic regulation involves Wnt/hedgehog/
Notch signaling� �NA damage-induced epigenetic altera-
tions� telomere shortening� and early senescence [��].
�ata of our and other studies at the early period after
radiation exposure demonstrate that ionising radiation
induces a complex response including not only �NA� �ut
a set of epigenetic changes� oxidative damage� mem�rane
viscosity and expression of surface antigens molecules
accompanied �y somatic mutations in exposed cells [�9].
The lowest RTL indices in a group Cherno�yl clean-
up workers after low-dose exposure were consistent
with linear dose-effect dependency. At recovery after
radiation exposure in ARS survivors we have found
an increased heterogeneity of RTL. This has to �e ex-
plained in future. One of the explanations is a stage
switching of reparative mechanisms� and possi�ly
telomerase and genes regulating T-loop. Previous
experimental studies [��] and study of cancer patients
give some support to such point of view� demonstrating
different gene involvement in response to low-� middle
and high-dose radiation. Influence of the heterogene-
ity of gene reactions triggering telomere shortening
at different radiation doses and rates on anti-cancer
immune control and cancer induction or promotion
have to �e elucidated in future.
ACKNOWLEDGMENTS
The authors thank �r Y.Y. Kudryavets� Head of the
Bank of Cell Lines from Human and Animal Tissues�
R.E. Kavetsky Institute of Experimental Pathology�
Oncology and Radio�iology of NAS of Ukraine� for
donating K-�6� cell line.
REFERENCES
1. Lansdorp PM. Telomeres, stem cells, and hematology.
Blood 2008; 111: 1759–66.
2. Moskalev AA. Aging and genes. S-Peterburg: Nauka,
2008. 191 p.
3. Regeczy N, Valent S, Kormos L, et al. Telomere length
analysis on cord blood cells by the flow-FISH method. Hae-
matologia 2002; 32: 265–9.
4. Gilson E, Londoсo-Vallejo A. Telomere length profiles
in humans: all ends are not equal. Cell Cycle 2007; 6: 2486–94.
5. Neuhof D, Ruess A, Wenz F, Weber KJ. Induction
of Telomerase Activity by Irradiation in Human Lymphoblasts.
Radiat Res 2001; 155: 693–97.
6. Mathieu N, Pirzio L, Freulet-Marriere MA. Telomeres
and chromosome instability Cell Mol Life Sci 2004; 61: 641–56.
7. Rubio MA, Kim SH, Campisi J. Reversible manipula-
tion of telomerase expression and telomere length. Implications
for the ionizing radiation response and replicative senescence
of human cells. J Biol Chem 2002; 277: 28609–617.
8. Yablokov AV, Nesterenko VB, Nesterenko AV. Cher-
nobyl: consequences of catastrophe for a human and nature.
Nauka, 2007. 376 p.
9. Effros RB. Replicative senescence of CD8 T cells
potential effects on cancer immune surveillance and immu-
notherapy. Cancer Immunol Immunother 2004; 53: 925–33.
10. Amundson SA, Do KT, Vinikoor LC, Lee RA, et al.
Integrating global gene expression and radiation survival pa-
rameters across the 60 cell lines of the National Cancer Insti-
tute Anticancer Drug Screen. J. Cancer Res 2008; 68: 415–24.
11. Rudolph KL, Millard M, Bosenberg MW, DePin-
ho RA. Telomere dysfunction and evolution of intestinal car-
cinoma in mice and humans. Nat Genet. 2001; 28(2):155–159.
12. Castella M, Puerto S, Creus A, Marcos R. Telomere
length modulates human radiation sensitivity in vitro. J Toxicol
Lett 2007; 172: 29–36.
13. Ivanov V, Tsyb A, Gorsky A, Maksyutov M et al. Leuke-
mia and thyroid cancer in emergency workers of the Chornobyl
accident: Estimation of radiation risks (1986–1995). Radiat
Environ Biophys 1997; 36: 9–16.
14. Han D, Hosokawa T, Aoike A, et al. Age-related en-
hancement of tumor necrosis factor (TNF) production in mice.
Mech Ageing Develop 1995; 84: 39–54.
15. Willeit P, Willeit J, Mayr A, Weger S, et al. Telomere
Length and Risk of Incident Cancer and Cancer Mortality.
JAMA. 2010; 304(1): 69–75.
16. Scheinberg P, Cooper JN, Sloand EM, Wu CO, et al. As-
sociation of Telomere Length of Peripheral Blood Leukocytes With
Hematopoietic Relapse, Malignant Transformation, and Survival
in Severe Aplastic Anemia. JAMA. 2010; 304(12): 1358–1364
17. Mikhel’son VM, Gamaleо IA. Telomere shortening
is the main mechanism of natural and radiation aging. Radiats
Biol Radioecol 2010; 50: 269–75.
18. Kulkarni S, Ghosh SP, Hauer-Jensen M, Kumar
KS. Hematological targets of radiation damage. Curr Drug
Targets 2010; 11:1375–85.
19. Vosianov A, Bebeshko V, Bazyka D. Health effects
of Chornobyl accident: DIA, Kiev, 2008. 508 р.
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