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Minchenko et al. / International Journal of Radiation Medicine 2001, 3 (3-4): 106-117
3apel{JWR 1O.1v1.,A6pClJ1106B1O. HOBbIe aHTl1reHbI TKaHeBOH COBMeCTI1MOCTHL1eJIOBeKa.Me,[lI1I.:(I1Ha, MocKBa, 1986, 174 c.[Zaretskaya Yzl.ll1., Abramou VYzI. New Antigenes of Human Tissue Compatibility. Meditsina Publishing House,ivloscow, 1986, 174 p.]
H6axJ-teJ-tlcoAI AIIropHTMbI MeTO,[la rpyrrnoBoro )"-IeTa apryMeHToB npl1 HenpepbIBHbIX 116l1HapHbIX npH3HaKax. TIpenpl1HT AH YKpaI1HbI, Kl1eB,1992.[IuakbnenkoA. G. Algori thms of Methods of Group Accountof Arguments at Unceasing and BinalY Signs. Preprint,Academy of Sciences of Ukraine, Kiev, 1992].
H6axJ-teHlCO AI, 3au1.£eJ-tJCofO.fl., JI.uMump06 B,l1,. TIpHH5!Tl1e peIlleI-IHH Ha OCHOBe caMOOpraHl13aI.:(HH. COBeTCKoe pa,[lHO, MocKBa, 1976,21 C.[IuakbnenkoA. G., Zaycbenko YlI.P., Dimitrou YD. DecisionMaking on the Base of Self-organization. Soviet Radio Publishing House, Moscow, 1976,21 p.]
MuJ-t1.£eJ-lJCOJK.H. feHeTI1L1eCKHe CHCTeMbI KpOBH L1eJIOBeKa npH pa,[lHaI.:(110HHOM 06JIYLleHHH.JJ:I1CC.... ~\OK.6HOJI. HayK, Kl1eB, HI1I1 reMaTOJIOrl1HH nepeJII1BaH!15! KpOBH M3 YKpaI1HbI, 1995,326 C.
. [Mincbenko].N. Genetic Blood Systems at Exposure toRadiation. Dissertation of Doctor of Biological Sciences,Kiev, Research Institute for Haematology and Blood Transfusion, 1995, 326 p.].
MuJ-t1.£eJ-tlcoJK.H., JIecpmep A.B., KaJluJ-tu1.£eJ-tJCoc.E. I1HTerpl1pOBaHHa5! cpe,[la.[(JI5! CTaTHCTI1L1eCKOH06pa60TKH 3KcnepHMeHTaJIbHbIX ,[IaHHbIX MeTO,[laMI1 nonyJI5!I.:(HOHHOH CTaTI1CTHKH MEDSTAT. B KH.:
TIporpaMHble npo,[IyKTbI YKpal1Hbl. KaTaJIOr, 1994,BbII1.2, C. 34-35.[Mincbenko}.N., LejrerA. v, KalinclJenkoS.B. Integrated Environment for Statistical Processing of Experimental Datawith Methods of Population Statistics MEDSTAT.Catalogue«Software of Ukraine·>, 1994, Issue 2, pp. 34-35.]
ne6J-tUl{JCUUJIA. CTaTI1CTHLleCKa5! OI.:(eHKa aCCOI.:(l1aI.:(I1HHLA-aHTl1reHOB C 3a60JIeBaHH5!MH. BeCTH. AMHCCCP, 1988,7: 48-51.[Peunitsky L.A. Statistical evaluation of associations of I-ILA-antigens with diseases. Vest. AMN SSSR, 1988,7: 48-51]
np02paMMbt npRMo2o CUJ-tme3aMooeneu (no npl1HI.:(l1nycaMoopraHH3aI.:(I1H).I1HCTI1TyT KH6epHeTHKH, KHeB,BbII1.1-3, 1975.[Programmes oj Direct Syntheses oJ Models (on the principle ofself-organisation). Institute of Cybernetics, Kiev, Issues. 1-3, 1975]
CmenaJ-t06a E.M. TIpOrH0311pOBaHI1e 3,[10pOBb5!l1eTeHpaHHero B03paCTa. 113,[1aTeJIbCTBOTOMcKoro yHI1BepCHTeTa, TOMCK, 1987, 156 C.[Stepanoua E.I. Health Forecasting in Children of Early Age. ThePublishers of Tomsk University, Tomsk, 1987, 156 p.]
Wa6anuJ-t BH., Cepo6aJI,ll,. MI1HWIeCKa5! HMlVryHOreMaTOJIOfl15!. Mel1l1I.:(I1Ha,JIeHI1Hrpa,[l, 1988, 310 c.[SlJahaljn VN., SerouaL.D. Clinical Immunohaematology, Meditsina Publishing House, Leningrad, 1988, 310 p,]
BebeslJko VG., MinclJenkoj.N. Immunogenetic bloodfactors in ARS patients. In.: Proceedings of the EuropeanFederation ofImmunological Societies. 10th Meeting, 1012 September 1990, Edinburgh, 1990, pp. 3-11.
Kissmeyer-Nielsen F, SvejegaardA., Hauge M. Genetics of the human HLA transplantation system. Nature,1968, 219(159): 1116-1119.
Mattiuz PL., Inde D, PiazzaA. et al. HistocompatibilityTesting. Copenhagen, 1970, pp. 193-205.
MinclJenkoj. (,MEDSTAT·>. Catalogue of Exhibitors &Their Production in the Ukrainan Stand of the Innovation
Forum, Kyiv, 1995, pp. 74-75.Simons M., Tait B (Eds.) Detection of immune-associ
ated genetic markers of human disease. Churchill livingstone, London, 1984.
Svejgaard A., Hauge M., ]ersild C. The HLA System:Monographs in Human Genetics. Basel. 1975, vol. 7,pp.127-134.
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Stepanova, Misharina / International Journal of Radiation Medicine 2001, 3 (3-4): 118-122
CYTOGENETICAL EFFECTS IN PERIPHERAL BLOOD LYMPHOCYTESAMONG CHILDREN IN REMOTE TERMS AFTER PRENATAL
IRRADIATION
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E.!. Stepanova,].A. MisharinaResearch Centre for Radiation Medicine, Academy of Medical Sciences of Ukraine.
\'VHO Collaborating Centre53 Melnikov Street, Kiev, 04050, Ukraine088511318
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Abstract
Though the chromosome structural anomalies incidence elevation is marked in remote terms after the Cherno
byl accident among children exposed to acute irradiation in prenatal period. Stable damage is prcvalent with
identified breaks preferred localisation in 1,2, 3, 5, 7, 11, 13, 17 chromosomes. Both stable and unstable induced
chromosome aberrations with 1,4,5,9, 17,22 chromosomes elevated damaging are observed in children ex
posed to chronic radiation impact.
Keywords: children, prenatal irradiation, radiation Jeffect, aberration chromosomes.
INTRODUCTION
After the Chernobyl accident a cytogenetic exami
nation of reprcsentatives of different categories
of the irradiated contingents, including children
population exposed to ionising radiation in the
different periods of ontogenesis, was carried outby native and foreign scientists (Stepanova E.!.,
1996). Using the data obtained, possibility of cy
togenetic parameter usage as the most correct biological indicator of human irradiation was con
firmed, as well as necessity of further data storage
concerning frequencies, types and features ofhu
man genome damage in the remote period of the
Chernobyl catastrophe was indicated (Pilinskaya M. et a!., 1998).
As it is generally known the mutagenous effect in
duced by ionising radiation in human somatic and
sex cells can cause some pathologic states with the
genetic component (including oncopathology and
haemoblastoses), therefore the frequency of chro
mosome abnormalities in peripheral blood lymphocytes is considered as one of criteria of in
creased risk for the irradiated contingent.
Concerning this studies of small doses of ionisingradiation effect on a genome of somatic cells is now
represen ted as one of the most actual problems. An
assessment of the structural damages in chromosomes, which are markers of radiation effect is of
the great importance.
118
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Stepanova, Misharina / International Journal of Radiation Medicine 2001, 3 (3-4): 118-122
One of the most effective methods, permitting torealise a bio-indication of radiation effect, as well
as to identify the chromosomal nature of geneticaldisorders is the method of differentiated G-colour
ing, which allows not only to reveal structural damages, but also to establish a localisation of sites witha heightened chromosomal fragility (Ohtaki K.,
1992).
SUBJECTS AND METHODS
In remote period after the Chernobyl catastrophe42 children exposed to ionising radiation duringintrauterine development and 15 children of control group were examined.
The first group consisted of 22 children, born bypregnant at moment of the accident who were evacuated
from Pripyat (they can be referred to the variant ofacute single according to the type of irradiation).
The second group included 20 children exposed toionising radiation as during intrauterine development, as further years of life (living in N arodichsk)'district of Zhitomir region);
The third group (control) consisted of 15 children(date of birth - 1986) living in «clear» regions according to the radiation conditions.
The equivalent radiation doses to foetal red bonemarrow during acute irradiation ranged from 10 to376 mSv, and during chronic irradiation of children,including the antenatal period - from 4.7 to 52 mSv
A cytogenetic examination conducted after thecomplex clinical examination and medicogenetic
consultation of nuclear proband family, both basicand control groups. Thus, diseases related to disorders of DNA repair and chromosome instabilitywere eliminated. For 3 months before examinationchildren did not suffer from diseases of virus infec
tion, they were not under exposure to prophylactic inoculation, i.e. the majority of factors whichcould influence the results of cytogenetic analysiswere eliminated.
The complex clinical and cytogenetic examinationsof children of 10-12 years old were conducted.
For preparations of metaphase chromosomes to beobtained the heparinised blood was cultivated dueto standard semimicromethod in the nutrient me
dium HAM'S F-l °«<Seromed», Germany), contain
ing L-glutamine, with an addition of embryoniccalves serum «<Seromed», Germany) and phytohemagglutinin (PHA-M, <·Difco>" USA) for48-50 hours(the last 2 hours - with a colchicine, <.Merk», Ger
many). This allowed to analyse cells which weremainly presented in the first postradiation mitosis.
The preparations were obtained after hypotonictreatment (0.075 M solution KCl at temperature37 'C) and thrice-repeated fixing with ethanol and
O,lJ,HHMH3 HaH60JIee .3cpcpeKTHBHbIXMeTO,lJ,OB,KOTOpbIHrr03BOJI5IeToCYIl~eCTBJI5ITb6HOHH,lJ,HKaIJ;HlOpa,lJ,HaIJ;HOHHoro B03,lJ,eHCTBillI,a TaIOKeH,lJ,eHTHcpHIJ;HpOBaTbXpOMOCOMHYJOrrpHpo,lJ,y reHeTH'-IeCKHX HapyrneHHH, 5IBJI5IeTC5IMeTO,lJ,,lJ,HcpcpepeHIJ;HpOBaHHoH G-oKpacKH, KOTOpbIHrr03BOJI5IeTHe TOJIbKOBbI5IBHTbCTPYKTYpHble rrOBpeJK,lJ,eHillI, HO H YCTaHoBHTb JIOKaJIH3aL\HlOcaHToB rroBbIIlleHHOH JIOMKOCTHXpOMOCOM (Ohtaki K., 1992).
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119
Stepanova, Misharina / International Journal of Radiation Medicine 2001, 3 (3-4): 118-122
glacial acetic acid in ratio 3:1.For obtaining differentially G-coloured chromosomes the preparationswere dipped into Trypsin (2 S mg: 100 ml of distilledwater) for 4 seconds. To colouring Gimza's methodwas applied.
Cytogenetic analysis was carried out using a visualkaryotyping of individual chromosomes. Not lessthan 200 metaphases responding to necessary requirements were analysed in each examined pa
tient. All the aberrations of chromosome (translocation, deletion, inversion, acentric fragments, dicentrics and ring chromosomes) and chromatid
(single fragments, exchanges) types (with the exception of gaps) were taken into account.
RESULTS AND DISCUSSION
The results of cytogenetic examination of childrenof control group testify to that the mutation rate inthe somatic cells was at the population level. So, amean frequency of aberrant cells and chromosome
aberrations in group, showed through structuralabnormalities of both chromosome and chroma
tid types, being identical was 2.71±0.61 %.The aberrations of chromosome type were representedmainly by pair fragmcnts (0.57±0.23%) and anomalous monocentrics (mainly by terminal deletionswithout acentric fragments) (0.43±0.15%). Thenumber of aberrations with chromatid type was1.57±0.38%, which were represented only by singlefragments.
In children examined at the age of 10-11, whose redbone matTOW was inadiated during intrauterine development in doses from 10 to 376 mSv, the amountof the aberrant cells (8.66± 1.23%) and the mean frequency of chromosome aberrations (9.07±1.34%)exceeded parameters of the control (P<O.oS). Thus,the individual frequency of aberrant chromosomesranged from 2 up to 18.5 per 100 cells. In 17 childrenthe level of abenant cells exceeded 3%.The majorityof chromosome damages were represented by theabetTations of chromosome type (7.2±1.l7%), whilethe stable structural abnormalities (translocation, inversion, deletions) were registered in 21 children andconsisted of S.64±0.94%, that significantly exceededthe control parameters (P<O.OS). The unstable chromosome damages were registered with the frequency of 1.43±0.3 S%and were mainly represented by pairfragments, dicentric and ring chromosomes, that canbe a consequence of abenation preservation of thistype aswell as in the founder cells, and in the fraction
of long-living peripheral lymphocytes.
The number of aberrations of chromatid type (single fragments and exchanges) was 2±0.2S% and itdid not differ from data on the children in control
group (P>O.OS).
In children exposed to ionising radiation as in periodof prenatal development as at further stages of ontogenesis (chronic type of irradiation) and with the
120
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Stepanova, Misharina / International Journal of Radiation Medicine 2001, 3 (3-4): 118-122
equivalent exposure dose to red bone marrow for all
the pedods from 4.7 up to S2mSv, the mean frequency of the aberrant cells and chromosome aberrations
in groups was 7.1S±2.39% and 7.63±2.92% respectively
and exceeded parameters of the control (P<O.OS).
The individual frequency of aberrant metaphasesranged from 1.5% up to 21 %. Thus the level of aber
rant cells exceeded 3% in 14 children. The majority
of the registered damages was represented byaberrations of chromosome type and was 77%.
The mean group level of unstable markers of irra
diation (dicentric and ring chromosomes) (1.75±0.25%) significantly exceeded the parameters of the
control (P<O.OS). The significant augmentation of
stable (4.23± 1.06%) chromosome damages (P<O.OS)was also marked. Translocations and inversions
were registered in 14 children of them. Their mean
group frequency was 0.73 per 100 cells and statisti
cally significantly exceeded parameters of the control. The level of deletions also significantly exceed
ed parameters of the control (P<O.OS) and was
(3.38±0.87%). The terminal deletions were prevailedin a spectrum of deletion chromosomes.
The aberrations of chroma tide type were registered
with the frequency of 1.6S±0.2% and corresponded to control group (P>O.OS).
The determination of a damage degree in somebands during formation of stable and unstable aber
rations allowed to establish the significant exceed
ing of an amount of breakages in chromosomes ofexposed groups in comparison with the control.
The comparative analysis of point distribution inchromosome breakage has shown non-random al
location of chromosome damages (proportionally to the chromosome length and DNA contents in
them). However, for the first group the preliminarylocalisation of the identified breakages is characteristic in 1,2,3, 5, 7, 11, 13, 17 chromosomes. Chro
mosomes 6, 10, 15,21, X were less damaged.
The increased damage of 1,4, 5,9, 17,22 chromo
somes was observed in the second group. in 6, 8,
10, 19,20 chromosomes the breakages were registered less often. The localisation of the heightened
fragility fields, that is characteristic for both groups,
is shown in table. It is necessary to mark, that nodamages of Y chromosome were detected as in
main as in control groups.
The predominant localisation of break points wasmarked in euchromatin sites of chromosomes, where
it is registered about 90% of all damages is registered.
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121
Stepan ova, Misharina / International Journal of Radiation Medicine 2001,3 (3-4): 118-122
For establishment of possible correlation between
the frequency, type of structural damages in chromosomes and equivalent exposure doses of red
bone marrow it was carried out correlation analysis. In children exposed to acute prenatal irradia
tion in the dose range from 10 up to 376 mSv the
availability of authentic correlation connection
between the frequency of aberrant cells (r=0.34),chromosome aberrations (r=0.39), as well as stable
chromosome damages of the apparatus (r=0.33)and equivalent exposure doses of red bone marrow
were established. Such dependencies were not es
tablished in chronic type of irradiation to red bone
marrow in the range from 4.7 to 52 mSv.
Thus, in children exposed to acute prenatal irradi
ation, the increase in the frequency of structural
chromosome anbnormalities with a predomina
tion of stable damages and primary localisation ofthe identified breakages in 1, 2, 3, 5, 7, 11, 13, 17chromosomes is marked in remote terms after the
Chernobyl accident. In children exposed to chron
ic irradiation the augmentation both stable and un
stable induced chromosome aberation and heightened damage of 1,4,5,9,17,22 chromosomes areobserved.
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122
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11.3KBI1BaJIeHTHbIMI1,l.103aMI106JTy'IeHI15I KpacHoro KOCTHoro M03ra rrpOBe,l.1eH KOppeJI5I~I10HHbIH aHaJII13. Y ,l.1e
TeH, rrO,l.1BeprIIII1XC5IoCTp0MY BHYTPHYTP06HOMY 06JTy'Ie1-II1IOB W1arra30He ,l.103OT 10 ,l.10 376 M3B, YCTaHOBJIeHO
lIaJII1qI1e ,lJ;OCTOBepHoH KOppeJI5I~I10HHOH CB5I3I1Me~qaCTOTOH a6eppaHTHblx KJIeTOK (r=0,34), a6eppa~I1H
XpOMOCOM (r=0,39), TaK)Ke cTa6I1JIbHbIX rrOBpe)K)J;erII1HXpOMocoMHoro arrrrapaYa (r=0,33) 11 .3KBI1BaJIeHTHbIMl1
,lJ;03aMl106JTy'IeHl15I KpaCHoro KOCTHOrO M03ra. TIpl1 xpoHl1qeCKOM Tl1rre 06JTy'IeHl15I KpacHoro KOCTHoro M03ra,lJ;03aMI1B,l.1l1arra30He OT 4,7 ,lJ;052 M3B TaKlIX 3aBl1Cl1MOC
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TaKIIM 06pa30M, B OT,lJ;aJIeHHbIeCpOKlI rrOCJIe aBapl1l1 Ha
'LfA3C y ,l.1eTeH,nO,lJ;BeprIIIlIXC5IOCTp0MY BHYTPHYTP06HO-
. MY06JTy'IeHl1IO, OTMeQaeTC5I rrOBblIIIeHl1e QaCTOTbI ClPYKTypHbIX aI-IOMaJIl1HXpOMOCOM C rrpeBaJIl1pOBaHl1eM CTa6l1JIbHbIXnOBpe)K)J;emIH 11rrpel1MYIIIeCTBeHHOH JIOKaJI113a
~l1eH I1,l.1eI-ITHcj:>l1~I1pOBaI-IHbIXp;13pbIBOB B 1, 2, 3, 5, 7, 11,
13-H 1117 -H XpOMOCOMax Y ,lJ;eT~H,nO,lJ;BeprIIIlIXC5IXPOHl1QeCKoMY pa,z:J;I1a~I10I-IHoMYB03,lJ;eHCTBmO, Ha6mo,lJ;aeTC5I
YBeJIl1QeI-II1eKaK CTa6l1JIbHbIX, YaK 11HeCTa6l1JIbHbIX l1HAY~l1pOBaHHbIX XpOMOCOMHbIX a6eppa~l1H 11nOBblIIIeHHa5I
rrOBpe)K)J;aeMOCTb 1,4, 5,9, 17 -H 1122-H XpOMOCOM.
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RETt'RN t1~is ioan to: CAS
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