[Genomic instability in chidren born after the Chernobyl nuclear accident (in vivo and in vitro studies)].

Analysis of peripheral blood lymphocytes in children born after the accident at the Chernobyl Nuclear Power Plant in the period from 1987 to 2004 (permanent residents of territories contaminated with radionuclides, n = 92; and children of irradiated fathers-liquidators, n = 88)) revealed increased levels of aberrant cells (ACs) and aberrations of the chromosomal type as compared to the control (P < 0.05). In three subgroups of children with different initial AC frequencies (children with high AC frequencies, > or = 3%; children with medium AC frequencies, 2%; and children with low AC frequencies, > or = 1%), the levels of aberrations of the chromosomal type are increased as compared to the control (P < 0.05). The levels of aberrant cells and chromosome aberrations (CAs) in the subgroup of children with > or = 3% frequencies significantly differ from those in the subgroup of children with > or = 1% AC frequencies. No dependence of the AC and CA frequencies on the year of birth after the Chernobyl accident was revealed. After fractional and single gamma-irradiation (137Cs) of blood in vitro in the 10-30 cGy dose range, the average CA frequencies in the first and second mitoses increased in a similar way depending on the initial AC frequencies in the children and parents. All these results suggest an individual character ofgenomic instability induced by low radiation doses and its transgenerational phenomenon in the organisms of children.

[Transgenerational genomic instability in children of liquidators of the accident at the ChNPP (cytogenetic and immunogenetic characteristics)].

A complex of cytogenetic and of immunogenetic study of the state of the lymphocyte genomes in the liquidators of the ChNPP accident and their unirradiated children has been carried out for the first time. Increased frequencies of the chromosome aberrations, of gene mutations (TCR mutations) and of predictors of apoptosis (cells with CD95+ immunophenotype) have been revealed in both generations. The analysis of correlations between the parameters under study has demonstrated distinctive features characteristic of induction of genomic instability in the organism of unirradiated children as compared to their fathers--liquidators directly exposed to radiation. Individual variability of genome destabilization were observed by all criteria used and manifested themselves in the diverse spectrum of transgenerational mutational effects and in different levels of their expression. The results obtained demonstrate the necessity of integral evaluation of the state of the genome using several genetic criteria to reveal transgenerational genomic instability in children of a special category--the offsprings of irradiated parents.

[The organization of medical aid to children of various cohorts of supervision, undergone to the influence of small dozes of radiation].

In clause the stages of organization of medical aid to children who undergone to the influence of the ecopathologic factors, including small dozes of ionizing radiation are submitted. The features of various stages of medical aid in nearest time after influence of the radiating agent are shown. The methodological complexities of diagnostic measures in the late times after the ecopathologic influence of small dozes of ionizing radiation are submitted, the role of the radiosensitivity in formation of pathological somatic diseases of condition at children is considered. The opportunity of the differential treating and preventive help rendering to the children various cohorts of supervision is shown.

[The problem of induced genome instability as the basis of the increased morbidity in children exposed to low-intensity radiation at low doses].

The main results of the complex examination of the genome instability are presented in children constantly living on territories contaminated with radionuclides as a result of the accident at the CNPP (Novozybkov district, Bryansk region, 16-18 Ci/km2, 137Cs) and in children exposed to low-intensity radiation at different stages of ontogenetic development: children exposed to postnatal irradiation in 1986 (born before the accident), children exposed to intrauterine irradiation during the accident in 1986, children of irradiated parents born after the accident in 1987-1992 and in 1994-2000. In all examined groups of irradiated children increased frequencies of certain radiation-induced chromosome aberrations were observed as well as a reduced activity of unscheduled synthesis of genomic DNA in lymphocytes and peculiarities in individual heterozygosity of genes encoding structural and enzymatic proteins of blood. An increased radiosensitivity of lymphocyte genomes to testing in vitro irradiation and peculiarities in the dynamics of the frequencies of chromosome aberrations and sister chromatid exchanges in 3 cell generations were revealed in children from the contaminated areas. The data obtained suggest a systemic character of dysgenomic effects, the reality of induction of genome instability in the growing organism of children exposed to low-intensity radiation at low doses the expression of which is determined by individual genotypic features of the organism. Biological significance of the phenomenon of the post-radiation genome instability, its relation to the state of health and the pathogenetic role in the development of somatic pathology are postulated.

[Polygenomic realization of mutagenic effects in the body of people exposed to low-dose radiation]. / Poligenomnaia realizatsiia mutagennykh éffektov v organizme liudei, podvergaiushchikhsia vozdeistviiu radiatsii v malykh dozakh.

A concept of polygenomic realization of mutagenic effects in the human body exposed to low-dose radiation on the basis of cell reproductions of genomic damages (Nig = 2n/2) was suggested. The above-said is in agreement with the principles of non-threshold mutagenic action of radiation and biological amplifier, and lead to the development of polygenomic dysbalance with pathophysiological consequences.

[Biochemical mechanisms of radiogenic cytogenetic and somatic disorders in children residing in regions polluted by radionuclides]. / Biokhimicheskie mekhanizmy radiogennykh tsitogeneticheskikh i somaticheskikh narushenii u detei--rezidentov zagriaznennykh radionuklidami regionov.

Children and adults affected by the Chernobyl accident suffer with lipoperoxic stress coupled with hypovitaminoses A and E, the syndrome and its radiogenic mechanisms described by the authors previously. The relation of these biochemical disturbances to somatic consequences on mutagenic and teratogenic levels caused by chronic low-dose irradiation of children into radiopolluted regions has been investigated. Either the rational approaches to prevent or/and to treat all pathologies indicated were tested. The radionuclide polluted regions had 1-5, 5-15 and 15-40 Ci/km2 by 137Cs. Unprotected newborns (without the therapy) had vA and vE levels about one third of normal ones for minimal radioloads, the vitamins lowered further for higher Da and/or Dm up to the deep hypovitaminoses or even avitaminoses. Increasing of LPC catabolites levels for children were correlated significantly with their stigmation levels. The therapy-protected newborns had normal ranges of all indices. However, unprotected newborns showed dramatic increase for all of radiogenic indices along with fall of vA and vE, and significant inverse correlations of the indices with retinol levels. The values of radiogenic indices showed hyperbolic-like rise along with growing of vA and vE deficits below their lower limits. The combination of radiogenic biochemical deviations evaluated for Chernobyl contingents is supposed to be the primary molecular mechanisms of somatic mutations and irreversible stigmation. The peroral polyvitamin therapy is proposed as the method of choice for prevention or normalization of revealed pathologies.

[Expression of genomic instability in lymphocytes from children living under conditions of long term exposure to radioactive factors]. / Ekspressirovanie genomnoi nestabil'nosti v limfotsitakh detei, prozhivaiushchikh v usloviiakh dlitel'nogo deistviia radiatsionnogo faktora.

An experimental study of expression of genomic instability was carried out with the use of testing irradiation in peripheral blood lymphocytes of 15 children (born in 1986-1998) living on territories with radionuclide contaminations (over 15 Ci/km2, 137Cs, Novozybkov district, Bryansk region). In 5 children exposed to intrauterine irradiation in 1986 this phenomenon was studied in 3 successive cell generations (mitoses). The data obtained suggest the reality of expression of induced genomic instability in the offsprings of repeatedly divided cells of a growing organism exposed to prolonged action of low radiation levels.

[The problem of induced genomic instability in the child body cells under conditions of long-term effect of small radiation doses]. / Problema indutsirovannoi genomnoi nestabil'nosti v detskom organizme v usloviiakh dlitel'nogo deistviia malykh doz radiatsii.

The phenomenological aspects of the genomic instability induced in the descendants of the multi-divided cells having been exposed to the radiation are examined. It is demonstrated that the regularity of the chromosome instability induction do not correspond to the classical conception of the radiation genetics (hit principle and target theory). The mechanisms and the biological significance of this new genetic phenomenon in the child organism under conditions of low-intensive effect of small-dose radiation and its connection with the state of health are discussed.

Biodosimetry results obtained by various cytogenetic methods and electron spin resonance spectrometry among inhabitants of a radionuclide contaminated area around the siberian chemical plant (Tomsk-7).

On April 6, 1993, near the town of Tomsk (Russia) there was an accident at the Siberian Chemical Plant (SCP) which resulted in extensive contamination of an area of 250 km(2) to the north of SCP with long-lived radionuclides such as (239)Pu, (137)Cs and (90)Sr. Cytogenetic methods and electron spin resonance (ESR) spectrometry of tooth enamel were used to estimate the radiation doses received by the population. The ESR signal intensity and the chromosomal aberration frequency in lymphocytes of the tooth donors showed a good correlation. The data showed that 15% of the inhabitants of the Samus settlement received a radiation dose >90 cGy. The exceptions were results of an examination of fishermen, where ESR gave high values (80-210 cGy) but both the chromosome assay and the cytokinesis block micronucleus method gave lower ones (8-52 cGy). A large increase in chromosome damage was observed in people born between 1961 and 1969. It was found that during these years several serious accidents at the Siberian Chemical Plant had occurred causing radiation pollution of the area. The number of cells with chromosome aberrations was significantly less among the people arriving in Samus after 1980. We found good correlations between the level of carotene consumption and a decrease in frequency of both micronuclei in binucleated lymphocytes (r = 0.68, P < 0.01) and chromatid aberrations (r = 0.61, P < 0.01) among the inhabitants. We also examined the inhabitants of Samus for opisthorchis infection, which was present in 30% of the population. The Samus inhabitants affected by Opisthorchis felineus showed significantly increased levels of micronuclei in binucleated lymphocytes and chromatid aberrations as compared with the controls.

[The cytogenetic effects in the population of the Altai Territory subjected to ionizing radiation exposure as a result of the nuclear explosions at the Semipalatinsk proving grounds]. / Tsitogeneticheskie éffekty u naseleniia Altaishogo kraia, podvegshegosia vozdeistviiu ioniziruiushchikh izluchenii v rezul'tate iadernykh vzryvov na Semipalatinskom poligone.

The cytogenetic examination of 178 persons living in seven settlements of the Altai region exposed to ionizing radiation during Semipalatinsk nuclear tests in 1949-1962 was carried out. It was shown that more than 80% of absorbed dose was due to the first nuclear explosion in 1949. The frequency of chromosome aberrations (dicentrics and rings) significantly exceeded the control level. The linear correlation between the dicentrics and rings frequency and absorbed dose was found. The cells with more than one aberrations were revealed in irradiated persons. This is supposed to be the result of 239Pu alpha-radiation.

[Comparative analysis of variability in a complex of anthropometric traits in full-term and premature neonates]. / Sravnitel'nyi analiz izmenchivosti kompleksa antropometricheskikh priznakov u donoshennykh i nedonoshennykh novorozhdennykh.

Variations of four anthropometric traits (body weight, body length, circumference of head, and circumference of chest) were compared in 149 premature and 819 full-term newborns. The average value of every studied trait for premature newborns was much less than that for full-term newborns. In premature boys, the correlation between body weight and length and circumferences of head and chest was substantially decreased. The coefficient of linear correlation between body mass and body weight for premature newborns was higher than that for full-term newborns. This was accounted for by the peculiarities of growth of the fetus during late prenatal development. Premature, boys and girls, in contrast to full-term children, did not differ considerably in the average values of the anthropometric traits studied. Therefore, the differences between newborn boys and girls in weight and size (sexual dimorphism) are formed at the last month of prenatal development.

[The joint variability of the growth-weight characteristics and biochemical gene markers in newborn infants]. / Sopriazhennaia izmenchivost' rosto-vesovykh kharakteristik i biokhimicheskikh markerov genov u novorozhdennykh.

A relationship between heterozygosity of 6 biochemical loci and variability of 4 anthropometric traits at birth has been studied in 304 boys and girls from Moscow population. All 4 traits in boys are positively correlated with the number of loci for which they are heterozygous. The values of all the traits in girls are highest in homozygous individuals. In order to reduce the number of variables the principal component analysis is applied. Boys and girls with average level of heterozygosity turned out to be closest to the corresponding population averages of morphological traits. The results are discussed in terms of 3 models: Lerner's concept of genetical homeostasis, additive and overdominance polygenic models. It is concluded that an average level of heterozygosity is optimal for a population.

[Frequency of rare electrophoretic protein variants in normal human beings and in congenital pathology]. / Chastota redkikh élektroforeticheskikh belkovykh variantov u cheloveka v norme i pri vrozhdennoi patologii.

17 blood proteins of infants with rough and multiple congenital malformations (CM), prematurely born infants and sick newborns without developmental anomalies were studied electrophoretically in polyacrylamide and starch gels (62422 locus tests). The control included blood samples of healthy newborns from ordinary maternity hospitals (60234 locus tests). The frequency of rare protein variants in all the cases was higher in sick children than in healthy ones. The frequency of rare genes (corrected for electrophoretically "silent" alleles) was 2.16 X 10(-3) in infants with CM and 0.99 X 10(-4) in the control. Examination of parents of 11 congenitally malformed infants with rare protein variants showed that at least in 5 cases such variants were absent in the parents and might be attributed to "fresh" mutations. However, only 3 variants (1 for serum albumin and 2 for red cell esterase) represented rare heterozygotes with codominant expression. This corresponds to the frequency of 0.59 X 10(-3). In the total population of newborns the proportion of infants with CM was 0.02, which means that the population mutation rate is 1.18 X 10(-5) per gene per generation. The data obtained support the conclusion about strong pressure of stabilizing selection against de novo mutations which change electrophoretic mobility of the protein molecule. The reasons for discrepancy between our data and the recent results of Neel and Mohrenweiser (1984) are discussed.

Cytogenetic effects of epoxy resin in man: dependence on sex, age and period of exposure.

The cytogenetic analysis of 156 subjects occupationally exposed to epoxy resin has revealed sex-dependent differences: average frequencies of aberrant metaphases and chromosome breaks per cell were significantly higher in males than in females. No linear or other functional relationship between the frequency of aberrant metaphases and the period of exposure to the resin has been revealed. However, a significantly higher average frequency of aberrant metaphases was observed in the group of elderly workers with a long period of exposure. The distribution of individuals according to the frequency of aberrant metaphases in the control group does not differ significantly from Poisson's law, while in individuals exposed to epoxy resin it is closer to the normal distribution.

[Assessment of the frequency of rare electrophoretic variants of blood proteins in children with congenital pathology]. / Otsenka chastoty redkikh élektroforeticheskikh variantov belkov krovi u detei s vrozhdennoi patologiei.

The frequency of rare electrophoretic protein variants was studied in children with congenital anomalies. The stated frequency (1.07 X 10(-3] proved to be ten-fold higher than in the control group of newborns (1.09 X 10(-4). This difference was mainly due to rare variants of monomorphic proteins. The data obtained confirm the assumption of a functional importance of monomorphic protein loci.

[Genetic anomalies in dysmenorrhea and sterility: range and frequency, age-related dependence, mosaicism dynamics]. / Geneticheskie anomalii pri dismenoreiakh i besplodii: spektr i chastota, vozrastnaia zavisimost', dinamika mozaitsizma.

Cytogenetic examination of 304 women with different breaches of menses accompanying sterility revealed 8,6% patients having chromosomal anomalies: 14 women had karyotype 45,X; 5 patients had the XY complex of sexual chromosomes, 3 patients having the mosaic set of chromosomes 45,X/46,XX; and a group of patients were with karyotypes 45,X/46,XX/47,XXX; 45,X/46,XXq-/46,XX; 47,XXX; 46,Xq- represented each by one case. The highest frequency (37%) and the most various spectrum of chromosomal anomalies were revealed among women with primary amenorrhea. The intensity of mutagenesis on the genome level with regard to X-chromosome was in average 100 times higher than on the chromosomal (structural) level. Genealogical analysis has revealed the X-linked recessive inheritance of the "XY-women" syndrome in one family and also permitted to suppose 2 autosomal-recessive forms of primary amenorrhea with karyotype 46,XX in 5 patients. Other cases were sporadic. In spite of the higher risk of indivergence of sex chromosomes in gametogenesis for parents of old age groups, the probability of birth of children with chromosomal anomalies considered in not increased with the age of parents. A tendency to the increase in a relative number of cells with the normal karyotype was detected at the pubertal age in mosaic organisms due to selective processes.