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.     

Complex cytogenetic characteristic of people suffered from Chernobyl accident

A cytogenetic study was performed on Chernobyl cleanup workers, on their children, on persons evacuated from contaminated aeria (adult and children), on so named "veterans of particular risk" irradiated due to the accidents on the nuclear plant, testing of nuclear weapons etc. and on control donors. The yield of stable (FISH analysis) and of unstable chromosome aberrations, micronuclei in both lymphocytes and erythrocytes, HPRT mutations was found to be increased in exposed groups as compared to control ones. In children of liquidators and in evacuated children we observed genomic instability and increased in vitro chromosomal radiosensitivity. Acceleration of age accumulation of translocations characterized the exposed population in comparison with control group. People with the highest level of routine chromosome aberrations had cardiovascular and digestive diseases more often likely than those with the lowest level. In frame of International Project ECP-6--"Biological dosimetry" the dose-responses for dicentrics and translocations were constructed in dose range 0-100 cGy of gamma-irradiation on the base of data of 8 laboratories. On cancer patients undergone whole-body gamma-irradiation (every day at the dose 11.5 cGy to a total of dose 57.5 cGy) we constructed the dose-responses for the dicentrics and translocations and compared them with the dose-responses for these aberrations after the in vitro irradiation of lymphocytes of the same patients. For the dicentrics the effectiveness of the in vivo irradiation was less than of the in vitro one. No differences were found for translocations.     

Postnatal effects in children irradiated during the intra-uterine development, as a result of failure at the Chernobyl NPP

Somatic and genetic effects at children who have undergone the influence of ionizing radiation during in utero development and at the subsequent stages ontogenesis are investigated, in view of dozes of the general irradiation and equivalent dozes of an irradiation of red bone brain. 1144 children were examined: 1st group consisted of children who have been born from women pregnant at the moment of failure, evacuated from Pripyat; 2nd group included children who have been born from women pregnant at the moment of failure, stayed to live in a zone of the strict radiation control; 3rd group was the control group--children who have been born in 1986, living in safe region of the Ukraine according to radiation conditions. The presence of direct correlation link between quantity of small anomalies of the development and the total radiation dose of the fetus (R = 0.61, p < 0.002) and inverse link with fetus age at the moment of radiation factor effect (R = -0.53, p < 0.003) has been established. Significant correlation links between the total radiation dose and the level of children health (R = 0.45, p < 0.03); the equivalent radiation dose of the red bone marrow and the frequency of damages in the chromosomal apparatus of the somatic cells (1st group--R = 0.51, p < 0.02; 2nd group--R = 0.62, p < 0.002) have been revealed.     

The problem of the transgeneration phenomenon of genome instability in sick children of different age groups after the accident at the Chernobyl Nuclear Power Plant

A complex genetic examination of children which belong to two cohorts and their parents were carried out. The first cohort included children and constantly living on territories contaminated with radionuclides (Novozybkov district, Bryansk region). They were subdivided in groups according to the ontogenetic age periods of development of their parents at the time of the Chernobyl accident. In the children born in 1986-1995 the level of aberrant genomes is significantly higher as compared to the control (p < 0.001). In children born in 1998-2002 the differences are insignificant (p > 0.05). The frequency of aberrant genomes had a tendency to decrease with the period of time between the birth date of a child and the moment of the accident. Analysis of the results of cytogenetic investigation for the same living on territories with different densities of radioactive contamination (zone I-- 627-688 kBq/m2, 137Cs and zone II-- 135-402 kBq/m2, 137Cs) revealed insignificant differences in the spectrum and average frequencies of chromosome aberrations. The second cohort included children born in 1987-1991 and 1993-2002 from irradiated fathers (Chernobyl clean-up workers) and unirradiated mothers living on territories without radionuclide contamination. These children also displayed increased frequencies of aberrant genomes as compared to the control (p < 0.001). The analysis of the dynamics years of birth of cytogenetic disturbances in the same cohorts of children showed the average frequencies of aberrant genomes remain higher than the control level. In most of the children of both cohorts the repair synthesis of genome DNA by gamma- and UV-radiation is reduced as compared to one in the children from the control group.     

Mortality in the offspring of individuals living along the radioactively contaminated Techa River: a descriptive analysis

From 1949 onwards, radioactive waste was released into the Techa River in the southern Urals and the population living along the river was exposed to ionising radiation. Relocation of these people did not start until several years later, causing many individuals to be exposed to substantial doses from internal and external radiation. The identification and follow-up of the exposed individuals started more than 40 years ago and is still continuing. The Techa River offspring cohort (TROC) that has recently been established, comprises 10,459 children born to at least one parent living along the Techa River during the period 1950-1992. Of these children, 3,897 were born during the period of highest release, i.e. between 1950 and 1956 and might thus have been exposed in utero. A total of 1,103 individuals have since died mainly due to infectious and respiratory diseases, injury and poisoning. Only 25 cases were identified as having died of a malignant condition. The radioactive contamination of the Techa River in the southern Urals gives a unique possibility to study the adverse effects of protracted exposure to ionising radiation in a large well-described cohort. The Techa River offspring cohort will make it possible to study the effects on those exposed in utero or early in life and the follow-up of the cohort in the future is, therefore, of great importance. Comparisons with other cohorts of humans exposed early in life, will increase our knowledge in this field of research.     

Prenatal exposure: The effects of prenatal cocaine and methamphetamine exposure on the developing child

Prenatal substance use remains a significant issue in the United States. Initial reports regarding prenatal cocaine and methamphetamine exposure suggested profound adverse effects on child development. However, subsequent prospective, longitudinal investigations have found more subtle effects. What follows is a brief review of the health, growth, behavioral, and intellectual outcomes for children exposed to prenatal cocaine and prenatal methamphetamine. Factors that may mitigate or intensify subtle adverse effects manifested in exposed children will also be discussed. Birth Defects Research (Part C) 108:142–146, 2016. © 2016 Wiley Periodicals, Inc.     

Evaluation of the effect of the radioactive contamination of hydrobionts in the 30-kilometer control zone of the accident at the Chernobyl AES]

A study was made of hydrobionts, particularly fishes, living within the thirty-kilometer control zone of Chernobyl NPP and northern part of the Kiev basin, after the disaster. Out of 31 fish species living in the NPP cooling pond some were identified which were mostly affected by radioactive contamination. They were predators belonging, with respect to reproduction and development, to a lithophilous group. Peculiarities of reproduction of Hypophthalmichthys molitrix kept in stews of the cooling pond before the accident were studied. After a three-year exposure to ionizing radiation (cumulative dose of 8-9 Gy) no reduction in the reproductive capacity of mature fishes was observed.     

The accident at Chernobyl and outcome of pregnancy in Finland.

OBJECTIVE--To evaluate the outcome of pregnancy in Finnish women after the accident at the Chernobyl nuclear power plant on 26 April 1986. DESIGN--Geographic and temporal cohort study. SETTING--Finland divided into three zones according to amount of radioactive fallout. SUBJECTS--All children who were exposed to radiation during their fetal development. Children born before any effects of the accident could be postulated--that is, between 1 January 1984 and 30 June 1986--served as controls. INTERVENTIONS--Children were divided into three temporal groups: controls, children who were expected to be born in August to December 1986, and children who were expected to be born in February to December 1987. They were also divided, separately, into three groups according to the three geographic zones. END POINT--Incidence of congenital malformations, preterm births, and perinatal deaths. MEASUREMENTS AND MAIN RESULTS--There were no significant differences in the incidence of malformations or perinatal deaths among the three temporal and three geographic groups. A significant increase in preterm births occurred among children who were exposed to radiation during the first trimester whose mothers lived in zones 2 and 3, where the external dose rate and estimated surface activity of caesium-137 were highest. CONCLUSIONS--The results suggest that the amount of radioactive fallout that Finnish people were exposed to after the accident at Chernobyl was not high enough to cause fetal damage in children born at term. The higher incidence of premature births among malformed children in the most heavily polluted areas, however, remains unexplained.     

Quantitative and noninvasive assessment of prenatal X-ray-induced CNS abnormalities using magnetic resonance imaging

Our purpose was to noninvasively assess formation of the microvasculature, blood-brain barrier (BBB) and blood-CSF barrier formation of prenatal X-ray-induced CNS abnormalities using quantitative MRI. Eight pregnant female Sprague-Dawley rats were divided into two groups consisting of control and X-irradiated animals. After birth, 20 neonatal male rats were divided into four groups of five rats. To evaluate the development of the BBB, changes in T(1) induced by Gd-DTPA were compared quantitatively in normal and prenatally irradiated animals in the formative period 1 to 2 weeks after birth. To assess the abnormalities of the microvasculature, quantitative perfusion MRI and MR angiography were also used. Histology was also performed to evaluate the BBB (albumin) and vascular endothelial cells (laminin). Decreased cerebral blood flow (CBF) and angioarchitectonic abnormalities were observed in the prenatally irradiated rats. However, abnormalities of the BBB and blood-CSF barrier were not observed using Gd-enhanced MRI and albumin staining. Quantitative perfusion MRI, MR angiography and Gd-enhanced T(1) mapping are useful for assessing CNS disturbance after prenatal exposure to radiation. These techniques provide important diagnostic information for assessing the condition of patients during the early stages of life after accidental or unavoidable prenatal exposure to radiation.     

Chromosome instability revealed in children of fathers irradiated during Chernobyl accident

Four children groups with and without thyroid pathology born to fathers exposed to ionizing irradiation in 1986 during Chernobyl accident as liquidators as well as residents of territory with radioactive contamination have been cytogenetically observed. The frequency and spectrum of chromosome aberrations in peripheral blood lymphocytes have been studied using two-termed cultivation (during 48 and 144 hours). Under the short-term incubation the observed groups did not significantly differ on the mean-group integral cytogenetic parameters which corresponded to age norm, but in progeny of parents from radionuclide contaminated territory the increased level of chromosome type exchanges has been revealed. In long-termed lymphocyte cultures of children with chronic thyroiditis the significantly increased cytogenetic effects of both chromatid (single fragments) and chromosome types (abnormal monocentrics, centric rings) have been established. The data received testified the reality of the transmissible chromosome instability phenomenon in progeny of irradiated parents and confirmed the possibility of its expression in consequent mitoses.     

Studies concerning the effects of low level prenatal X-irradiation on postnatal growth and adult behaviour in the Wistar rat

Fifty-nine pregnant Wistar strain rats were sham irradiated or subjected to a 0.1 or 0.2 Gy exposure of X-radiation on the 9th or 17th day of gestation. Twenty-seven of the females were killed at term for teratologic analysis. The remaining mothers raised their young. At 60 days of age the 252 offsprings were randomly assigned three of six tests: open field, swimming, hanging, activity wheel, water T-maze, or conditioned avoidance response. Male offspring exposed at the 0.2 Gy level exhibited retarded growth only during the first few weeks of postnatal life. Female offspring exposed on the 17th day to 0.2 Gy X-radiation were growth retarded throughout the test period. Postnatal growth rates, however, were not significantly different between the irradiated and control groups. There were no significant alterations in adult behaviour due to prenatal X-irradiation. There were sex differences in activity wheel and forelimb hanging performance, unrelated to radiation exposure. These results indicate that prenatal low level X-irradiation on the 9th or 17th day of gestation does not result in significant alterations in adult behavioural performance in the rat, but prenatal growth retardation persists postnatally. Growth may be a more sensitive indicator of the effects of prenatal exposure to X-radiation than postnatal behaviour.     

Development of genetic instability in mice in response to chronic irradiation simulating high-altitude flight conditions

The purpose of this work was to study the chronic influence of the high-energy radiation field formed in the atmosphere at an altitude of 10 to 30 km on the level of DNA damage in leukocytes of peripheral blood in mice. The external radiation field (behind the concrete shield) of the U-70 accelerator (Serpukhov, Russia) was used for these studies. This radiation field simulates the components and spectral composition of the high-energy radiation field formed in the atmosphere at an altitude of 10 to 30 km. Two groups of SHK line mice were chronically irradiated with a total dose equivalent to 21.5 and 31.5 cGy. The state of the genome of nucleated blood cells was assessed by the Comet assay (alkaline version) 72 h after completion of chronic irradiation. The level of genome damage in individual peripheral blood leukocytes of irradiated animals was compared with the basal level of DNA lesions in peripheral blood leukocytes of unirradiated control mice. The damage was expressed in %TDNA (the amount of DNA found in the "comet tail" in percent of total DNA in the "comet"). It was found that in mice exposed to the radiation field of the accelerator, the mean value of DNA damage was: %TDNA = 3.88 +/- 0.35% for a dose of 21.5 cGy and % TDNA = 6.00 +/- 0.82% for a dose of 31.5 cGy. In mice irradiated at an X-ray therapeutic device with a dose of 150 cGy 24 h before the examination, %TDNA was 2.27 +/- 0.34% and this did not differ from %TDNA in unirradiated mice, 2.68 +/- 0.56%. We suggest that the increased level of DNA damage observed in mice irradiated with 31.5 cGy from the mixed radiation field at the Serpukhov accelerator points to the development of genetic instability in their leukocytes as a result of chronic exposure of animals to this particular radiation field.     

Clinical immunological disorders in children from various observation cohorts exposed to radiation factor during various stages of oncogenesis

The immune status disorders and features depending on the radiation impact type in various cohorts of radiation observations long after the Chernobyl (CNPP) disaster and the possible role of these disorders in development of chronic somatic pathology in children are shown. Lymphocyte depletion, T-cell immunity component disorders in the form of cell contraction with CD3, CD4, CD8 markers and the B-cell immunity component disorders in the form of reducing the quantity of CD10, CD23 marker cells were observed in children subject to combined chronic irradiation by 131I, 137Cs, 90Sr radionuclides. The descendants of irradiated parents (the 1st generation; children of the Chernobyl accident consequences liquidators, children of the citizens of radiation contaminated territories with various 137Cs levels) had immunity disorders of different type. A change in the total amount of NK-cells (CD16(+)-lymphocytes) is the general sign for all radiation risk groups; however, people subject to direct radiation impact demonstrated reduction of the antitumor protection potency, whereas descendants of irradiated ones demonstrated its activation with typically increasing number of CD16(+)-lymphocytes. In all radiation risk groups, a tendency to reduction of a number of cells involved in the leukocytal activation with the "pluripotential activation" marker (CD38 marker cells), proliferating cells (CD71 marker cells) and the increase of relative amount of cells with apoptosis marker (CD95(+)-lymphocytes). Immune disorder markers under the radiation impact in various cohorts of children's observation are suggested: antigens: CD4, CD8, CD10, CD23, CD16, CD38, CB71, CD95.     

Terahertz radiation improves adaptation characteristics in <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

An investigation into the effect of nonionizing terahertz radiation (0.1–10 THz) on living organisms is urgent due to the recent development of modern technologies employing such radiation. The aim of this study was to establish the impact of terahertz radiation on successive generations of fruit flies. The effects of terahertz radiation on the survival ability and lifespan of the Oregon-R strain of Drosophila melanogaster proved to be diverse: they were negative or neutral at early life stages and positive at late stages. The female flies exposed to the radiation showed increased survival rate during the second half of the life of imago. The males demonstrated low sensitivity to the radiation. There were no significant differences noted in the dynamics of maturation and total number of offspring between the female flies that were exposed to the radiation and those that were not. The results of the study practically did not depend on the sex and maturity stage of the oocytes irradiated.     

Cytogenetic abnormalities of the descendants of permanent residents of heavily contaminated East Kazakhstan

More than 400 nuclear explosion tests were conducted at the Semipalatinsk Nuclear Test Site (SNTS) and significant radioactive substances were released. The long-term consequences of the activities at the SNTS and the appearance of any hereditary effects remain insufficiently studied about 25 years after the test site was closed. The population living in villages near the SNTS are considered to have been heavily exposed to external and internal radiation. This study aims to perform an assessment and comprehensive cytogenetic analysis of the inhabitants living near the SNTS, and their first-(F1) and second-(F2) generation children. Residents of the East Kazakhstan region living in the area covered by the former SNTS were included in the study. To evaluate the hereditary effects of nuclear testing, comprehensive chromosome analyses were performed in lymphocytes using conventional Giemsa and fluorescent in situ hybridization methods in 115 F1 and F2 descendants in the villages of Dolon and Sarzhal, which were heavily contaminated. The parents of the subjects had permanently lived in the villages. A higher number of stable-type chromosome aberrations such as translocations was found in these residents than in 80 residents of the control area, Kokpecty, which indicates the possibility that radiation had biological effects on the exposed subjects.     

Long-term cytogenetic effects in children prenatally-exposed to radiation as a result of the accident at the Chernobyl Atomic Energy Station

Forty-two children exposed to ionizing radiation in prenatal period and 15 children of control group were examined in the remote terms after the accident using the method of differential G-staining of chromosomes in lymphocytes of peripheral blood. It was found that the average group rate of aberrant cells and chromosome aberrations was reliably higher in the children exposed in utero compared to control. Long-term cytogenetic consequences of the pre-natal exposure were characterized by prevalence of aberrations of a chromosome type, mainly stable chromosome lesions. At chronic exposure to low doses of ionizing radiation the increase in the rate both stable and unstable chromosome aberrations.     

Minisatellite germline mutation rate in the Techa River population

Germline mutation at eight minisatellite loci has been studied among the irradiated families from the Techa River population and non-exposed families from the rural area of the Chelyabinsk and Kurgan Oblasts. The groups were matched by ethnicity, parental age, occupation and smoking habit. A statistically significant 1.7-fold increase in mutation rate was found in the germline of irradiated fathers, whereas maternal germline mutation rate in the exposed families was not elevated. Most of the minisatellite loci showed an elevated paternal mutation rate in the exposed group, indicating a generalised increase in minisatellite germline mutation rate in the Techa River population. These data suggest that the elevated minisatellite mutation rate can be attributed to radioactive exposure. The spectra of paternal mutation seen in the unexposed and exposed families were indistinguishable.     

GSM 900 MHz microwave radiation affects embryo development of Japanese quails

A wide range of non thermal biological effects of microwave radiation (MW) was revealed during the last decades. A number of reports showed evident hazardous effects of MW on embryo development in chicken. In this study, we aimed at elucidating the effects of MW emitted by a commercial model of GSM 900 MHz cell phone on embryo development in quails (Coturnix coturnix japonica) during both short and prolonged exposure. For that, fresh fertilized eggs were irradiated during the first 38 h or 14 days of incubation by a cell phone in "connecting" mode activated continuously through a computer system. Maximum intensity of incident radiation on the egg's surface was 0.2 μW/cm2.The irradiation led to a significant (p<0.001) increase in numbers of differentiated somites in 38-hour exposed embryos and to a significant (p<0.05) increase in total survival of embryos from exposed eggs after 14 days exposure. We hypothesized that observed facilitating effect was due to enhancement of metabolism in exposed embryos provoked via peroxidation mechanisms. Indeed, a level of thiobarbituric acid (TBA) reactive substances was significantly (p<0.05-0.001) higher in brains and livers of hatchlings from exposed embryos. Thus, observed effects of radiation from commercial GSM 900 MHz cell phone on developing quail embryos signify a possibility for non-thermal impact of MW on embryogenesis. We suggest that the facilitating effect of low doses of irradiation on embryo development can be explained by a hormesis effect induced by reactive oxygen species (ROS). Future studies need to be done to clarify this assumption.     

Health effects of low-level irradiation during development: experimental design and prenatal and early neonatal mortality in beagles exposed to 60Co gamma rays

As part of a long-term study of the effects of irradiation during development, prenatal and early neonatal mortality were evaluated for beagles exposed in utero at 8 days postcoitus (dpc), 28 dpc, 55 dpc, or 2 days postpartum. Mean doses used were 0,0.16, or 0.83 Gy. A decrease in whelping rates was observed for female breeders irradiated at 8 dpc. There was a significant decrease in litter sizes from female breeders irradiated at 8 and 28 dpc. Both of these findings are indicative of increased embryonic mortality. There was a significant decrease in the percentage of females born after exposures given at 28 dpc, indicating a differential radiosensitivity by sex. A significant increase in early neonatal mortality up to 14 days of age was observed for beagles exposed 8 or 28 dpc, again with an excess mortality in females.     

THE EFFECTS ON CHRONIC GAMMA RADIATION ON THE INTERNAL APICAL CONFIGURATIONS OF THE VEGETATIVE SHOOT APEX OF COLEUS BLUMEI

Clonal plants of a bushy variety ‘Trailing Queen’ of Coleus blumei Benth. were exposed to 600–700 R per day for 28 days. Shoot apices of control and irradiated plants were studied microscopically. The normal vegetative shoot apex has two tunica layers and a corpus which is partly layered and partly composed of randomly divided cells. Five cytohistological zones were observed, including a cup-shaped zone, imposed upon the tunica-corpus relationships. Response to gamma radiation resulted in abnormal internal apical configurations. All irradiated shoots was found to have the same internal configurations. Only a single tunica layer broken by occasional periclinal divisions was observed. The cytohistological organization of irradiated apices was different from that seen in the normal shoot tips in that two zones were found. Evidence of a radiosensitivity gradient within the vegetative shoot apex was also observed. The possible significance of the results is discussed.