Genetic effects in children exposed in prenatal period to ionizing radiation after the chornobyl nuclear power plant accident
Aim: To study the genetic effects in children exposed to radiation in utero as a result of the Chornobyl nuclear power plant accident accounting the total radiation doses and equivalent radiation doses to the red bone marrow. Materials and Methods: Incidence of minor developmental anomalies was stud...
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nasplib_isofts_kiev_ua-123456789-1377122025-02-23T20:28:29Z Genetic effects in children exposed in prenatal period to ionizing radiation after the chornobyl nuclear power plant accident Stepanova, Ye.I. Vdovenko, V.Yu. Misharina, Zh.A. Kolos, V.I. Mischenko, L.P. Original contributions Aim: To study the genetic effects in children exposed to radiation in utero as a result of the Chornobyl nuclear power plant accident accounting the total radiation doses and equivalent radiation doses to the red bone marrow. Materials and Methods: Incidence of minor developmental anomalies was studied in children exposed to radiation in utero (study group) and in the control group (1144 subjects surveyed in total). Cytogenetic tests using the method of differential G-banding of chromosomes were conducted in 60 children of both study and control groups (10–12-year-olds) and repeatedly in 39 adolescents (15–17-year-olds). Results: A direct correlation was found between the number of minor developmental anomalies and fetal dose of radiation, and a reverse one with fetal gestational age at the time of radiation exposure. Incidence of chromosomal damage in somatic cells of 10–12-year-old children exposed prenatally was associated with radiation dose to the red bone marrow. The repeated testing has revealed that an increased level of chromosomal aberrations was preserved in a third of adolescents. Conclusion: The persons exposed to ionizing radiation at prenatal period should be attributed to the group of carcinogenic risk due to persisting increased levels of chromosome damage. This article is a part of a Special Issue entitled “The Chornobyl Nuclear Accident: Thirty Years After”. 2016 Article Genetic effects in children exposed in prenatal period to ionizing radiation after the chornobyl nuclear power plant accident / Ye.I. Stepanova, V.Yu. Vdovenko, Zh.A. Misharina, V.I. Kolos, L.P. Mischenko // Experimental Oncology. — 2016 — Т. 38, № 4. — С. 272-275. — Бібліогр.: 23 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/137712 en Experimental Oncology application/pdf Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Original contributions Original contributions Stepanova, Ye.I. Vdovenko, V.Yu. Misharina, Zh.A. Kolos, V.I. Mischenko, L.P. Genetic effects in children exposed in prenatal period to ionizing radiation after the chornobyl nuclear power plant accident Experimental Oncology |
| description |
Aim: To study the genetic effects in children exposed to radiation in utero as a result of the Chornobyl nuclear power plant accident accounting the total radiation doses and equivalent radiation doses to the red bone marrow. Materials and Methods: Incidence of minor developmental anomalies was studied in children exposed to radiation in utero (study group) and in the control group (1144 subjects surveyed in total). Cytogenetic tests using the method of differential G-banding of chromosomes were conducted in 60 children of both study and control groups (10–12-year-olds) and repeatedly in 39 adolescents (15–17-year-olds). Results: A direct correlation was found between the number of minor developmental anomalies and fetal dose of radiation, and a reverse one with fetal gestational age at the time of radiation exposure. Incidence of chromosomal damage in somatic cells of 10–12-year-old children exposed prenatally was associated with radiation dose to the red bone marrow. The repeated testing has revealed that an increased level of chromosomal aberrations was preserved in a third of adolescents. Conclusion: The persons exposed to ionizing radiation at prenatal period should be attributed to the group of carcinogenic risk due to persisting increased levels of chromosome damage. This article is a part of a Special Issue entitled “The Chornobyl Nuclear Accident: Thirty Years After”. |
| format |
Article |
| author |
Stepanova, Ye.I. Vdovenko, V.Yu. Misharina, Zh.A. Kolos, V.I. Mischenko, L.P. |
| author_facet |
Stepanova, Ye.I. Vdovenko, V.Yu. Misharina, Zh.A. Kolos, V.I. Mischenko, L.P. |
| author_sort |
Stepanova, Ye.I. |
| title |
Genetic effects in children exposed in prenatal period to ionizing radiation after the chornobyl nuclear power plant accident |
| title_short |
Genetic effects in children exposed in prenatal period to ionizing radiation after the chornobyl nuclear power plant accident |
| title_full |
Genetic effects in children exposed in prenatal period to ionizing radiation after the chornobyl nuclear power plant accident |
| title_fullStr |
Genetic effects in children exposed in prenatal period to ionizing radiation after the chornobyl nuclear power plant accident |
| title_full_unstemmed |
Genetic effects in children exposed in prenatal period to ionizing radiation after the chornobyl nuclear power plant accident |
| title_sort |
genetic effects in children exposed in prenatal period to ionizing radiation after the chornobyl nuclear power plant accident |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2016 |
| topic_facet |
Original contributions |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/137712 |
| citation_txt |
Genetic effects in children exposed in prenatal period to ionizing radiation after the chornobyl nuclear power plant accident / Ye.I. Stepanova, V.Yu. Vdovenko, Zh.A. Misharina, V.I. Kolos, L.P. Mischenko // Experimental Oncology. — 2016 — Т. 38, № 4. — С. 272-275. — Бібліогр.: 23 назв. — англ. |
| series |
Experimental Oncology |
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2025-11-25T04:38:00Z |
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2025-11-25T04:38:00Z |
| _version_ |
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| fulltext |
272 Experimental Oncology 38, 272–275, 2016 (December)
GENETIC EFFECTS IN CHILDREN EXPOSED IN PRENATAL PERIOD
TO IONIZING RADIATION AFTER THE CHORNOBYL NUCLEAR
POWER PLANT ACCIDENT
Ye.I. Stepanova*, V.Yu. Vdovenko, Zh.A. Misharina, V.I. Kolos, L.P. Mischenko
State Institution “National Research Center for Radiation Medicine of the National Academy of Medical
Sciences of Ukraine”, Kyiv 04050, Ukraine
Aim: To study the genetic effects in children exposed to radiation in utero as a result of the Chornobyl nuclear power plant accident
accounting the total radiation doses and equivalent radiation doses to the red bone marrow. Materials and Methods: Incidence
of minor developmental anomalies was studied in children exposed to radiation in utero (study group) and in the control group
(1144 subjects surveyed in total). Cytogenetic tests using the method of differential G-banding of chromosomes were conducted
in 60 children of both study and control groups (10–12-year-olds) and repeatedly in 39 adolescents (15–17-year-olds). Results:
A direct correlation was found between the number of minor developmental anomalies and fetal dose of radiation, and a reverse one
with fetal gestational age at the time of radiation exposure. Incidence of chromosomal damage in somatic cells of 10–12-year-old
children exposed prenatally was associated with radiation dose to the red bone marrow. The repeated testing has revealed that
an increased level of chromosomal aberrations was preserved in a third of adolescents. Conclusion: The persons exposed to ionizing
radiation at prenatal period should be attributed to the group of carcinogenic risk due to persisting increased levels of chromosome
damage. This article is a part of a Special Issue entitled “The Chornobyl Nuclear Accident: Thirty Years After”.
Key Words: Chornobyl nuclear power plant accident, prenatal exposure, minor developmental anomalies, chromosomal aberrations.
Assessment of prenatal radiation effects is one
of prioritized fields of contemporary radiobiology and
genetics. Peculiarities of fetal response to radiation
are identified with recognized critical period from ninth
till fortieth day upon conception. Risk of unfavorable
radiation effects is much higher at this period than that
in a case of fetal exposure at later terms [1].
Exposure of pregnant females to ionizing radiation
after the A-bombing in Hiroshima and Nagasaki re-
sulted in no excess of congenital malformations (CMF)
of dysplastic origin in children. Retardation of somatic
and intellectual development was however surveyed
in those children mainly exposed at 8–15 weeks
of prenatal life. Mental retardation was concomitant
to small head size in some children [2]. No such ef-
fects were found in persons exposed at prenatal period
among population of the villages along the Techa River
(Russian Federation) [3] and the Chornobyl nuclear
power plant (CNPP) accident survivors [4]. However,
some specialists point at the development of cogni-
tive disorders in persons exposed to ionizing radiation
in prenatal period [5–7].
Not only the CMF and sentinel phenotype incidence
than can be eliminated at antenatal period but the
minor developmental anomalies (MDA), i.e. small but
stable morphogenetic disorders appearing at early
stages of prenatal life, are recently proposed to esti-
mate the consequences of mutagenic and teratogenic
effects of environmental impacts [8, 9].
Cytogenetic method is one of the leading ap-
proaches for biological indication of radiation impact
in human. Classical method of analysis of solid stained
chromosomes is widely applied to assay the radiation-
induced chromosomal damage [10, 11]. However, this
method is not capable to reveal the entire spectrum
of chromosomal damage, thus presently the methods
of differential G-banding and fluorescent in situ hybridi-
zation of metaphase chromosomes with DNA-probes
(FISH) having high resolution are used more often [12].
Objective of this study was to explore the genetic
effects in children exposed at prenatal period to ioni-
zing radiation after the CNPP accident. Total radiation
doses and red bone marrow equivalent radiation doses
were taken into account.
MATERIALS AND METHODS
Assessment of aftermath of prenatal irradiation
was held in pediatric population (n = 1144) of the
3 groups. Study group I (n = 340) comprised children
born by females pregnant at the time of accident
who were evacuated from Prypyat city. Study group II
(n = 373) comprised children born by females preg-
nant at the time of accident who continued to live
in the areas with soil contamination density by 137Cs
over 555 kBq/m2 or 90Sr above 111 kBq/m2. In control
group (n = 431) were children born in 1986 who live
in radiologically safe region of Ukraine.
Total fetal radiation doses and fetal red bone mar-
row equivalent radiation doses did not differ and varied
from 10.0 to 376.0 mSv in the study group I. Cumula-
tive total radiation doses for the entire time of living
on contaminated territories including antenatal period
in children of the study group II were 10.5–72.1 mSv,
and integral equivalent red bone marrow doses were
14.1–81.7 mSv.
To reveal a range of antenatal risk factors the in-
terviewing of parents was applied with ascertaining
Submitted: June 13, 2016.
*Correspondence: E-mail: profstepanova@i.ua
Abbreviations used: CMF – congenital malformations; CNPP – Chor-
nobyl nuclear power plant; MDA – minor developmental anomalies.
Exp Oncol 2016
38, 4, 272–275
Experimental Oncology 38, 272–275, 2016 (December)38, 272–275, 2016 (December) (December) 273
of parental health, occupational features, presence
of bad habits if any, obstetrical and gynecological his-
tory, history of pregnancy and delivery in mother, and
reviewing of medical records in parents and children.
Clinical check-up and genetic testing included the
genealogical evaluation and identification of specific
phenotype features in each child from study and con-
trol groups. The special Protocol (Card) of registration
of the MDA was applied. It included 225 clearly reco-
gnizable dysembryogenic stigma grouped according
to an anatomical localization principle. Filling in the
Protocol provided the accuracy of MDA registration
with objective nature and comparability of received
data (there were 95% data agreement in repeated
check-up). Data on the present CMF and data on the
possible parental exposure to environmental mutagens
were entered into the Protocol too. Such approach
to assay the mutagenic and teratogenic effects
of environmental factors was applied also by the other
research teams [8, 9].
Cytogenetic studies were held upon a complex
clinical check-up and medical-genetic counseling.
Children have had neither acute nor exacerbation
of chronic diseases within three months before ex-
amination. No preventive vaccinations were introduced
too, i.e. principal factors that could make any bias
in cytogenetic tests were excluded. The first cytoge-
netic test was applied in 60 children 10–12-year-old
of the study group I (n = 23), study group II (n = 22),
and control group (n = 15). The repeated cytogenetic
examination was held in 39 children 16–17-year-old
of the study group I (n = 16) and study group II (n = 23).
Differential G-banding of chromosomes was
done according to the modified of Yunis [13]. Ap-
plication of this method enables to receive the early
mitotic chromosomes with high segmentation degree
(550–1500 in a haploid set) and to define their struc-
tural damage with identification of breakpoints at the
segment and subsegment levels [14]. The analysis
was held with a visual karyotyping of individual chro-
mosomes using oil immersion at × 1000 magnification.
At least 200 metaphases corresponding to the specific
requirements were analyzed in each subject. All the
chromosome type and chromatid type aberrations,
i.e. single fragments and exchanges were accounted
except gaps. Both unstable (i.e. free paired fragments,
acentric rings, dicentric chromosomes, and centric
rings) and stable aberrations (i.e. translocations, ter-
minal and interstitial deletions, para- and pericentric
inversions, insertions leading to formation of abnormal
monocentric chromosomes) were accounted as the
markers of radiation impact.
Data processing was held using the Microsoft
Excel and Statistica software. The Spearman’s rank
correlation non-parametric test (Ro) was calculated
allowing to set the relationship between qualitative
and quantitative characteristics [15].
All studies were performed as part of our clinical
standard procedures and within the approved indica-
tions. An analysis was approved by the Institutional
Review Board. Written informed consent was obtained
from all patients. No prospective experiments with
human subjects were performed and the study was
in accordance with the Helsinki Declaration and our
national regulations.
RESULTS AND DISCUSSION
Children of the study groups were not different from
the control group by the medical and biological risk
factors and bad habits in parents, i.e. smoking or alco-
hol abuse (Table). Impact of these factors along with
fetal radiation exposure predisposed to the increased
incidence of morphogenetic variants characterized
by multiple MDA. Number of such children in both study
groups I and II was higher vs that in control group: 43.2;
33.6, and 11.9%, respectively (р < 0.05).
Table. Incidence of some risk factors in children of the study and control
groups (%)
Risk factor Study group I
(n = 340)
Study group II
(n = 373)
Control group
(n = 431)
Occupational hazards in a father 19.2* 3.4 2.8
Bad habits in parents 20.8 21.6 25.1
Chronic somatic diseases:
– in a father 19.2 17.9 19.4
– in a mother 22.2 19.2 20.5
Late first delivery 12.9 13.4 10.4
Repeated deliveries after 35 years 18.5 19.2 20.1
Burdened obstetrical history 18.5 26.9 26.4
Complicated pregnancy 44.9 40.4 41.1
Complicated labor 57.4 59.6 61.7
Radiation factor 100.0 100.0 −
Note: *difference between the study and control groups is significant (р < 0.05).
Number of MDA per one child was 5.58 ± 0.26 in the
study group I, 5.13 ± 0.32 in the study group II, and
2.95 ± 0.16 in control (р < 0.001). The most pro-
nounced differences were found in the spectrum
of MDA in locomotor system where their average
amount in the study groups I and II twice exceeded
the values in control group (1.43 ± 0.10; 1.22 ± 0.09,
and 0.64 ± 0.06, respectively; р < 0.001).
A direct correlation was found between the MDA
number in a child and total fetal irradiation dose
(Rо = 0.61; р < 0.002), and a reverse correlation was
revealed between the MDA number and gestation
age at the time of radiation exposure (Rо = –0.53;
р < 0.003). The highest number of MDA was registered
in persons exposed to ionizing radiation in the terms
of 2 to 8 weeks of prenatal life (Rо = –0.91; р < 0.0001).
Consequently the lesser fetal gestation age was
at the time of irradiation and the higher radiation dose
was, the higher number of MDA has been revealed
in a child.
It is believed that impact of environmental of en-
dogenous teratogenic or mutagenic factors at early
terms of prenatal life can lead not only to the CMF
development but also to origination of small but stable
disorders of morphogenesis, i.e. MDA [8, 9].
Cytogenetic testing results indicate that the indices
in the control group were in general corresponding
to contemporary literature data on the spontaneous
levels of chromosomal aberrations in population and
were in agreement with conclusions of some experts
about the acceleration of spontaneous mutagenesis
274 Experimental Oncology 38, 272–275, 2016 (December)
during the last 10 years. The last fact can be related
to environmental degradation [16].
An increased incidence of structural chromosomal
anomalies (9.07 ± 1.34 per 100 cells vs 2.47 ± 0.28 in the
control group; p < 0.01) with domination of stable dam-
ages (5.64 ± 0.94 per 100 cells vs 0.43 ± 0.19 in control;
p < 0.05) and preferential localization in chromosomes
1, 3, 5, 7, 11, 13, and 17 were found at remote period
after the CNPP accident in children exposed to acute
irradiation in prenatal life (study group I). Majority of the
stable-type aberrations were represented by deletions
(4.18 ± 0.71 per 100 cells vs 0.37 ± 0.19 in control;
p < 0.05) with predominance of terminal ones. Trans-
locations and inversions found in about the same
incidence (0.70 ± 0.16 and 0.75 ± 0.15 in average per
100 cells, respectively) occurred much more rarely.
Unstable chromosomal aberrations found in 1.43 ±
0.35 per 100 cells vs 0.47 ± 0.13 in control (p < 0.05)
were represented by the acentric fragments (0.66 ±
0.18 per 100 cells), dicentric chromosomes (0.61 ±
0.15 per 100 cells) and ring chromosomes (0.16 ±
0.05 per 100 cells).
An average incidence of chromosome aberrations
in the study group II was 7.63 ± 2.92 per 100 cells
what significantly exceeded these values in control
group (2.47 ± 0.28 per 100 cells; p < 0.05). There was
an increased number of both stable (4.23 ± 1.06 per
100 cells vs 0.43 ± 0.19 in control group; p < 0.05)
and unstable (1.75 ± 0.25 per 100 cells vs 0.47 ±
0.13 in control group; p < 0.05) induced chromosomal
aberrations and a doubled damage of chromosomes 1,
4, 5, 9, 17, and 22. Deletions (3.38 ± 0.87 per 100 cells)
mostly of terminal type, translocations (0.48 ± 0.14 per
100 cells), and inversions (0.38 ± 0.06 per 100 cells)
were featured among the stable structural rearrange-
ments. Unstable chromosomal aberrations were rep-
resented by the acentric fragments (1.10 ± 0.19 per
100 cells), dicentric (0.46 ± 0.09 per 100 cells) and ring
chromosomes (0.20 ± 0.08 per 100 cells).
Number of chromatid-type aberrations in children
of the study group I (2.0 ± 0.25 per 100 cells) and study
group ІІ (1.65 ± 0.20 per 100 cells) was not significantly
different from these in control group (1.57 ± 0.28 per
100 cells; p > 0.05).
A moderately strong correlation of the fetal red bone
marrow equivalent radiation dose and number of aber-
rant cells (Rо = 0.50; p < 0.02), chromosome-type aber-
rations (Rо = 0.53; p < 0.01), translocations (Rо = 0.60;
p < 0.003), and deletions (Rо = 0.60; p < 0.003) was
found in prenatally irradiated children born to females
evacuated from the Prypyat city (study group I).
Significant correlation between cumulative equiva-
lent radiation doses to the red bone marrow for the
entire period of residence in contaminated areas and
the number of aberrant cells (Rо = 0.62; p < 0.002),
chromosome-type aberrations (Rо = 0.72; p < 0.0003),
stable (Rо = 0.64; p < 0.003) and unstable (Rо = 0.58;
p < 0.01) chromosome damages was found in children
who have experienced a prolonged exposure to radia-
tion factor both in utero and at later periods (study
group II). No dependence of the chromatid-type aber-
rations on red bone marrow irradiation dose was found.
Other researchers have also stated the increased
incidence of chromosome damage in peripheral blood
lymphocytes of children exposed to acute and long-
term irradiation at prenatal and postnatal periods [17,
18]. However, higher incidence of stable and unstable
chromosomal aberrations found in our study could
be related to application of differential G-banding with
much better resolution capacity than that of routine
solid staining method applied by other research teams.
Higher radiation doses received by the subjects in our
study could be of importance as well.
The repeated cytogenetic testing has revealed
higher incidence of chromosomal damage in 37.5%
of 15–17-year-old adolescents in the study group I and
in 30.4% of them in the study group II vs the control
group.
Incidence of chromosomal aberrations in adoles-
cents from the study group I was 3.60 ± 0.04% per
100 cells.
Integrally the 20 out of 22 autosomes were in-
volved in the revealed disorders. Among different
types of structural chromosomal rearrangements
the deletions and translocations (41.67 and 16.67%,
respectively) were the most prevalent. Inversions were
detected in 5.56%, dicentric chromosomes in 2.78%,
ring chromosomes in 5.56%, and paired fragments
in 5.56% of all accounted aberrations.
Incidence of chromosomal aberrations in adoles-
cents born and constantly living in radiologically con-
taminated regions (study group II) was 4.16 ± 0.04%
per 100 cells.
According to data analysis, the deletions and
translocations (62.0 and 10.0% of all injuries) were
most prevalent among all types of chromosomal re-
arrangements. Inversions and unstable aberrations
such as paired fragments and ring chromosomes
were found more rarely, namely in 4.0; 8.0, and 2.0%,
respectively. The 20 out of 22 autosomes were involved
in the revealed cytogenetic abnormalities.
In conclusion, the received results are indicative
of the positive trend. Incidence and spectrum of cy-
togenetic abnormalities are however exceeding the
spontaneous level of mutagenesis in 37.5% of adoles-
cents in the study group I and in 30.4% of them in the
study group II (р < 0.05) at the age of 15–17 years.
All these disorders highlight the destabilization of he-
reditary structures, thereby increasing the risk of mul-
tifactorial diseases, the high frequency of which was
observed by many researchers in children exposed
in utero [17–19]. Our results suggest that a phe-
nomenon of genome instability characterized by the
presence of multiple morphogenetic variants of MDA
and increased incidence of chromosomal aberrations
persisting for a long time is developed in individuals
exposed to radiation in utero. It is known that people
with high levels of structural chromosomal damage
can be attributed to the group of carcinogenic risk.
Translocations are the most common chromosomal
Experimental Oncology 38, 272–275, 2016 (December)38, 272–275, 2016 (December) (December) 275
abnormalities that are characteristic for hematologi-
cal malignancies and some solid tumors [20]. Studies
of the Japanese authors conducted in population that
had survived the A-bombing in Hiroshima and Nagasa-
ki have shown a correlation between the translocation
in cells of red bone marrow and leukemia [21]. There
is an evidence of increased cancer risk in persons
exposed to ionizing radiation in prenatal period to the
doses exceeding 0.5 Gy, whereas the effect of lower
doses remains debatable [22]. Impact of radioactive
iodine resulted in an increased incidence of papillary
thyroid cancer in children of all age groups including
the irradiated in prenatal period that is the very severe
unfavorable effect of the CNPP accident [23].
Thus, the increased levels of chromosome aberra-
tions may be used as a prognostic test for the selection
of carcinogenic risk groups among subjects exposed
to ionizing radiation in utero after the CNPP accident.
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