Twenty years after the Chernobyl accident: solid cancer incidence in various groups of the Ukrainian population

Several major international studies such as those performed on the A-bomb survivors, have shown a clear linkage between the exposure to ionizing radiation and the occurrence of various cancer types including leukemia. While these studies are mostly characterized by high dose rates, studies on populations exposed after the Chernobyl accident are in most cases characterized by low dose rates which are typical for occupational radiation protection. Here, data on more than 60,000 Ukrainian workers who participated in recovery operation works in Chernobyl in 1986–1987, more than 50,000 evacuees from the city of Prypyat and the 30 km zone, and about 360,000 residents of most contaminated territories are presented, which cover a period of observation from 1980 to 2004. For all cancers combined, statistically significant higher incidence rates than the national rates were found only for the recovery workers (standardized incidence ratio (SIR) 117.2%, 95% confidence interval: 114.1–120.3), while those for the other investigated groups were lower. In all groups under study a significant increase of thyroid cancer incidence rates has been registered. This increase appears to be associated, at least partly, with the fallout of radioiodine, and it was found not only in children, but also in adolescents and adults. For example, the most significant excess was found for male recovery workers corresponding to a factor of 8.0. It is important to keep in mind, however, that the contribution of confounding factors such as an intensified thyroid screening after the Chernobyl accident could not be quantified, in the present study. For female recovery workers there was also an excess of breast cancer over the national rates (SIR 190.6%; 95% confidence interval: 163.6–217.7%). An analysis of the two other groups (evacuees and residents of contaminated territories) gave controversial results: relative to the local standard there was a statistically significant excess, while comparison with the national level did not substantiate this conclusion.     

Doses of Ukrainian female clean-up workers with diagnosed breast cancer

The Chernobyl reactor accident in 1986 has caused significant exposure to ionizing radiation of the Ukrainian population, in particular clean-up workers and evacuees from the exclusion zones. A study aiming at the discovery of radiation markers of the breast cancer was conducted from 2008 to 2015 within a collaborative project by HZM, LMU, and NRCRM. In this study, post-Chernobyl breast cancer cases both in radiation-exposed female patients diagnosed at age less than 60 from 1992 to 2014 and in non-exposed controls matched for residency, tumor type, age at diagnosis, TNM classification as well as tumor grading were investigated for molecular changes with special emphasis to copy number alterations and miRNA profiles. Cancer registry and clinical archive data were used to identify 435 breast cancer patients among female clean-up workers and 14 among evacuees from highly contaminated territories as candidates for the study. Of these, 129 breast cancer patients fit study inclusion criteria and were traced for individual reconstruction of the target organ (breast) doses. The doses were estimated for 71 exposed cases (clean-up workers and evacuees from which biomaterial was available for molecular studies and who agreed to participate in a dosimetric interview) by the use of the well-established RADRUE method, which was adjusted specifically for the assessment of breast doses. The results of 58 female clean-up workers showed a large inter-individual variability of doses in a range of about five orders of magnitude: from 0.03 to 929 mGy, with median of 5.8 mGy. The study provides the first quantitative estimate of exposures received by female clean-up workers, which represent a limited but very important group of population affected by the Chernobyl accident. The doses of 13 women evacuated after the accident who did not take part in the clean-up activities (from 4 to 45 mGy with median of 19 mGy) are in line with the previous estimates for the evacuees from Pripyat and the 30-km zone.     

Results of cytogenetic studies of the consequences of the Chernobyl accident

The selected results of the cytogenetic studies of the Chernobyl accident consequences were summarised. The chromosomal aberrations were used as a method of biodosimetry for a dose assessment for victims during the initial period after the Chernobyl accident. A good correlation between doses calculated based on chromosomal aberrations (dicentrics) and severity of acute radiation syndrome observed in clinic was found. The biodosimetry based on conventional cytogenetic technique (dicentrics) has been unsuccessful for various groups (rehabilitation workers, evacuees, inhabitants of contaminated areas) sampled long time after the Chernobyl accident. The possible reasons of the failure are analysed. The original results of multiaberration cell yield observed in different cohorts of the Chernobyl victims are presented. The problems related to the phenomena are discussed.     

Mutation rates in scots pine (Pinus sylvestris L.) from the Chernobyl exclusion zone evaluated with amplified fragment-length polymorphisms (AFLPs) and microsatellite markers

Ionizing radiation is a strong mutagenic factor and, accordingly, elevated mutation rates would be expected in plants exposed to high chronic or acute radiation after the Chernobyl accident in 1986. Somatic mutations were analyzed in pines (Pinus sylvestris L.) planted before and after the Chernobyl accident and in control material of the same origin planted in sites with natural radiation. Microsatellites (SSRs) and amplified fragment-length polymorphisms (AFLPs) were investigated. The mutation rates for microsatellites were estimated as 2.8 × 10(-4)-7.1 × 10(-4) per locus for different irradiated tree populations; no mutations were detected in the controls. In the case of AFLPs, the observed mutation rates were 3.74 × 10(-3) -3.99 × 10(-3) and 1.06 × 10(-3) per locus for contaminated and control areas, respectively. Thus a statistically highly significant three-fold increase in number of mutations was found by the use of AFLP markers, indicating that ionizing radiation causes strong DNA damage across the entire genome and that AFLPs may be the appropriate marker system for this kind of analysis.     

Analysis of blood lymphocyte subsets in children living around Chernobyl exposed long-term to low doses of cesium-137 and various doses of iodine-131

Epidemiological studies have found that children living around Chernobyl have rates of respiratory tract illness that are higher than those seen in the area before the Chernobyl accident. The present study investigates the possible effects of radiation exposure on the composition of peripheral blood lymphocyte subsets in children living around Chernobyl. Two hundred nineteen healthy children and children suffering from recurrent respiratory diseases aged 6-14 years who received both low doses of radiation to the whole body from (137)Cs and various doses of radiation to the thyroid from (131)I as fallout from the accident were assessed 5 (1991) and 8-10 years (1994-1996) after the accident. A total of 148 healthy children and children suffering from recurrent respiratory diseases living in noncontaminated areas were also evaluated as controls. Children with recurrent respiratory diseases who lived around Chernobyl had a significantly lower percentage of T cells and a higher percentage of NK cells compared to control children with recurrent respiratory diseases during the study period. In contrast to the findings in 1991, a significant decrease in the percentage of helper-inducer cells was observed in children with recurrent respiratory diseases in 1994-1996. In contrast to 1991, there is a positive correlation between the percentage of helper-inducer cells, the helper-inducer/cytotoxic-suppressor cell ratio, and the dose of radiation to the thyroid of healthy children from (131)I in 1994-1996. There was a positive correlation between the dose of radiation to the thyroid from (131)I and the percentage of helper-inducer cells in children with recurrent respiratory diseases 5 years (1991) after the accident. Further, the dose of radiation to the thyroid from (131)I correlated negatively with the percentage of T and B cells and positively with the percentage of NK cells in children with recurrent respiratory diseases 8-10 years (1994-1996) after the accident. These results raise the possibility that long-term exposure to low doses of (137)Cs may have altered the composition of the T-cell subsets and NK cells in children with recurrent respiratory diseases. The differences in the composition of the peripheral blood lymphocyte subsets between healthy children and those with recurrent respiratory diseases may be attributed to long-term low-dose exposure of the whole body to radiation from (137)Cs and exposure of the thyroid to radiation from (131)I subsequent to the Chernobyl accident.     

Cancer risks in the Kaluga oblast of the Russian Federation 10 years after the Chernobyl accident

Cancer morbidity and mortality were studied in areas of the Kaluga oblast contaminated with radionuclides. The main objective of the study was to assess the influence of radiation exposure on existing levels of cancer morbidity and mortality. Time trends and relative population risks were analysed. Based on this analysis, it was concluded that the current levels of morbidity from cancers among the populations residing in the studied areas were primarily a result of a complex of factors which predated the exposure from the Chernobyl accident. However, there seems to be an unfavourable trend concerning malignant neoplasms of the respiratory organs for women residing in the contaminated areas. To date, no statistically significant effect of radiation on cancer morbidity (except for thyroid cancer in women) has been noted. The levels of cancer morbidity and mortality in the contaminated areas generally reflect the changes in cancer incidence in the oblast as a whole. The findings are consistent with international data on latent periods for the induction of radiogenic cancers and the biological effects for similar levels of exposure to populations residing in contaminated territories. Further studies are necessary in order to monitor possible effects that are related to the accident.     

Content of blood lipids and characteristics of dyslipoproteinemias in people exposed to radiation during the accident at the Chernobyl nuclear power station

Lipid and lipoprotein spectrum of the blood plasma was investigated and phenotyping of hyperlipoproteinaemias was carried out in men exposed to ionizing radiation and suffered from acute radiation illness as a result of the Chernobyl accident. An increase of the total cholesterol triglycerides and content frequency of atherogenic types of hyperlipoproteinaemias in comparison with average levels of population both a year and 3 years after irradiation was observed. No essential differences were found between the obtained indices 1 and 3 years after irradiation which testified to the stability of the revealed disturbances.     

The radiological situation before and after Chernobyl disaster

The nuclear reactor accident, which occurred on 26 April 1986 at Chernobyl, has been one of the greatest ecological disasters in human history. In our study we discussed the most recent data on the accident, and the natural and synthetic sources of radiation. According to the recent data, the air at Chernobyl had been contaminated with about 5300 PBq radionuclide activity (excluding rare gases), including 1760 PBq (131)I and 85 PBq (137)Cs. The highest radiation received by the liquidators (0.8-16 Gy), lower doses were received by the population which was evacuated or inhabited the contaminated areas (in which the level of (137)Cs activity deposited in the earth was 37 kBq/m(2)). In the European countries the highest mean radiation dose per year for the whole body in the first year after the accident was in Bulgaria (760 microSv), Austria (670 microSv) and Greece (590 microSv), while the lowest radiation dose was observed in Portugal (1.8 microSv) and Spain (4.2 microSv). In Poland the mean effective equivalent dose resulting from Chernobyl accident was 932 microSv and is close to the limited dose permitted in Poland, equalling 1 mSv/year. The highest radiation dose to thyroid was received by inhabitants of the states previously known as Bielskopodlaskie, Nowosadeckie and the north-east region of Poland. Lowest dose was received by inhabitants of the areas previously known as Slupski and Rzeszowski.     

The effect of Chernobyl accident on the development of malignant diseases--situation after 20 years

The accident that occurred at the Chernobyl Nuclear Power Plant in 1986, released large quantities of radionuclides--among them radioiodine--into the atmosphere, thereby raising public concerns about its influence on thyroid structure and function, especially the development of malignancy. There were even reports about 700 deaths due to thyroid carcinoma in Russian Federation, Ukraine and Belarus, resulting from the accident. In this review we discussed the incidence of thyroid cancer in different parts of the world, especially in heavily contaminated countries, as Ukraine and Belarus, and the possible link between radioisotope activity in the thyroid and the development of malignancy. The study carried out in Minsk showed 40-fold increase of the incidence of thyroid cancer in the years 1986-1994, in comparison to the period 1977-1985. An increase of the incidence of thyroid cancer has generally been observed in many countries after the Chernobyl accident. We focused on the factors that may have an influence on this phenomenon, especially diagnostic tests, health care, social and environmental factors, like iodine level in water and soil. The results of molecular biology studies, e.g. RET translocation in carcinoma type RET/PTC1 in elderly and RET/PTC3 in children, and expression Ax1 and Gas6 in children were reviewed as well. We also mentioned other thyroid diseases, like nodular goitre, cysts, the disturbance of thyroid function and autoimmunity, possibly linked to the radiation after Chernobyl accident. Data obtained from the regions near Chernobyl showed no increased risk of other types of malignancy (leukaemia, Hodgkin's and non Hodgkin's lymphoma) in 1986-1996. In this article the epidemiology of thyroid diseases in Poland was also reviewed.     

The dose estimation of woody plants in the long-term after the Chernobyl NPP accident

Dosimetric models have been developed to estimate the exposure doses of woody plants growing in the area contaminated by long-lived radionuclides. The models are parameterized based on the data obtained from the experimental plots in the south-west districts of the Bryansk region affected by radioactive fallout of the Chernobyl NPP accident. Doses are estimated to generative organs of pine trees from these plots. The contribution from various sources and types of ionizing radiation to the absorbed dose formation for these objects is determined.     

Risk of acute childhood leukaemia in Sweden after the Chernobyl reactor accident. Swedish Child Leukaemia Group.

OBJECTIVE--To evaluate the risk of acute childhood leukaemia in areas of Sweden contaminated after the Chernobyl reactor accident in April 1986. DESIGN--Population based study of childhood leukaemia diagnosed during 1980-92. SETTING--Coordinates for places of residence of all 1.6 million children aged 0-15 years; aerial mapped areas of Sweden heavily contaminated after the Chernobyl accident. SUBJECTS--888 children aged 0-15 years with acute leukaemia diagnosed in Sweden during 1980-92, identified with place of birth and residence at diagnosis. MAIN OUTCOME MEASURES--Risk of leukaemia in areas contaminated after the Chernobyl accident compared with the rest of Sweden and in the same areas before the accident. RESULTS--During six and a half years of follow up after the accident the odds ratio for acute leukaemia was 0.9 (95% confidence interval 0.6 to 1.4) in highly contaminated areas (> or = 10 kBq/m2) compared with the same areas before the accident. For the subgroup acute lymphoblastic leukaemia in children aged under 5 years at diagnosis the odds ratio was 1.5 (0.8 to 2.6). For all cases diagnosed after May 1986 in highly contaminated areas compared with areas of low contamination the odds ratio was 0.9 (0.7 to 1.3). For acute lymphoblastic leukaemia in children aged under 5 years at diagnosis the odds ratio was 1.2 (0.8 to 1.9) in highly contaminated areas compared with areas of low contamination. Dose-response analysis showed no correlation between the degree of contamination and the incidence of childhood leukaemia. CONCLUSION--There has been no significant increase in the incidence of acute childhood leukaemia in areas of Sweden contaminated after the Chernobyl reactor accident.     

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.     

Long-term effects of low-dose irradiation on human health.

The effects caused by low-dose irradiation differ from those caused by high-dose irradiation. At present only little is known about the long-term effects of chronical exposure of individuals and whole populations to low-dose irradiation. This problem particularly concerns people living in territories heavily contaminated with radioactive material due to Chernobyl Nuclear Power Plant accident. We investigated different parameters of the peripheral blood from 124 men, working at the "Shelter" object (demolished block IV of the nuclear power plant). In many cases the accumulated radiation dose (gamma-rays) was more than 50 rem. As control group we examinated 302 male donors (of the same age) from the Kiev blood-transfusion station. The studies revealed the following effects in the "Shelter" object workers: an increased manifestation of signs of common-inflammatory reactions, such as an increased number of leukocytes and absolute number of white blood cells, an unproportionally high number of monocytes and band neutrophiles, and an increase in plasma cytokine levels (interferon-alpha, tumor necrosis factor-beta but not interleukin-1beta). Ongoing studies are targeted to develop and introduce new methods and techniques to measure the frequency of DNA strand breaks in peripheral blood lymphocytes for the surveillance of persons working and/or living in a radioactively contaminated environment after Chemobyl accident.     

Leukemia incidence in the Russian cohort of Chernobyl emergency workers

Of all potentially radiogenic cancers, leukemia, a type of cancer of the blood, has the highest risk attributable to ionizing radiation. Despite this, the quantitative estimation of radiation risk of a leukemia demands studying very large exposed cohorts, because of the very low level of this disease in unexposed populations and because of the tendency for its radiation risk to decrease with time. At present, the Japanese cohort of atomic bomb survivors is still the primary source of data that allows analysis of radiation-induced leukemia and the underlying dose–response relationship. The second large cohort that would allow to study radiation-induced leukemia is comprised of individuals who were exposed due to the accident of the Chernobyl nuclear power plant in 1986. The objective of the present study was to estimate radiation risks of leukemia incidence among the Russian cohort of Chernobyl emergency workers, for different time periods after the accident. Twenty-five years after the Chernobyl accident and based on the results of the present study, one can conclude that the radiation risk of leukemia incidence derived from the Russian cohort of Chernobyl emergency workers is similar to that derived from the cohort of atomic bomb survivors: The time-averaged excess relative risk per Gray (ERR Gy⁻¹) equals 4.98 for the Russian cohort and 3.9 for the life span study (LSS) cohort; excess absolute risk decreases with time after exposure at an annual rate of 9% for the Russian cohort, and of 6.5% for the LSS cohort. Thus, the excess in risk of leukemia incidence in a population due to a single exposure is restricted in time after exposure by the period of about 15 years.     

The molecular and cellular consequences of the chernobyl accident

In this paper the results of research at 5–10 and 24 years after the Chernobyl accident are summarized. These results include the investigation of genomic instability, formation of the adaptive response, genome damage, and oxidative status. The studies were performed on cells in culture, mice, children and adults who lived in the contaminated areas, and liquidators of the consequences of the Chernobyl accident. Inhibition of cell proliferative activity, late cell death, and the increase in micronucleus and giant cell frequency were observed after the exposure of cells in culture in the accident zone followed by their culturing in laboratory conditions. In the progeny of the exposed cells, the effect of enhanced radiosensitivity was detected. Thus, it can be assumed that exposure of parental cells in culture in the area of the accident induced genomic instability that resulted in the development of various abnormalities in progeny cells. At the organism level, the Chernobyl zone exposure of mice caused an increase in radiosensitivity; as well, a decrease in the endotheliocyte density in the cerebral cortex and other brain tissues was observed. In the blood lymphocytes of children stimulated by PHA, a more than two times increase in micronucleus cell frequency was detected. A reduced number of individuals with significant adaptive response was found in both the juvenile and adult groups. In all investigated populations, an increased number of individuals with enhanced radiosensitivity were observed in response to low-dose radiation exposure. At 24 years after the accident liquidators were subjected to examinations, which revealed an increased frequency of cells with micronuclei and chromosome-type aberrations in blood lymphocytes, an elevated level of DNA double strand breaks, and a reduced level of reactive oxygen species compared to those of the control group. This means that the genomic instability that was accumulated by the residents of the contaminated regions and liquidators as a result of the accident leads to damage of the genetic apparatus, an increase in radiosensitivity, and hypoxia as late consequences that all are risk factors and increase the probability of the development of tumor and non-tumor diseases. The development of the above-mentioned pathological processes may occur in the distant future.

     

Age specific formation of doses in children exposed to radioactive caesium following the accident in the Chernobyl Nuclear Power Plant

Individual measurement data on radiological surveillance of people residing in the territories most radioactively contaminated following the Chernobyl accident are analyzed to provide a comparison of doses from caesium radionuclides to children and adults. The external doses to children does not exceed those to adult inhabitants of the same settlement. By the results of surveillance in 1986 more than 80 thousand inhabitants of the western areas of Bryansk region, a specific activity of caesium radionuclides and corresponding internal radiation dose rate in a number of settlements appeared at children age under 3 years old exceeding the appropriate parameters for adult inhabitants. Among persons evacuated from the contaminated areas, such excess in day of departure from an area averaged 3.8 for surveyed pairs the child-parent.     

The individual prognosis of the gravity and of the outcome of acute radiation disease based on immunological indexes

The information significance of the immunological indexes for the prognosis of gravity of course and of outcome of an acute radiation disease for the people after the exposure of ionizing radiation in clinically significant doses is studied. The value of indexes of the C-reactive protein contents, of the complement contents and of the titer of haemagglutinins in serum of a blood of 147 patients damaged at Chernobyl NPP accident as a result of external radiation gamma-exposure in combination with internal irradiation from the incorporation in an organism predominantly beta-emitting radionuclides were compared to the weight of acute radiation disease and its outcome (survival or loss). Was determined, that indexes of the contents of C-reactive protein in a peripheral blood during primary reactions on the irradiation (1-2 day after irradiation) and in latent period of disease (3-9 day after irradiation), and also titer of a complement on 3-9 day after irradiation can serve a source of information for the prognosis of probable gravity of a radiation injury and its outcome at irradiation of the man in clinically significant doses.     

A comparative analysis of the impact on biota and man in the 30 km zone of the Chernobyl NPP

A methodological approach is described for a comparative assessment of ionizing radiation effects on man and biota, based on the use of indices of radiation impact--ratios of actual exposure doses to environmental objects (including humans) and critical ones. As such doses, standards limiting radiation exposure and doses at which phenotypical effects were absent after the Chernobyl accident were employed, respectively for man and biota. For the test site chosen within the 30 km ChNPP zone (region of the Borshchovka settlement), dose burdens to reference biota species and the population (with and without evacuation) and the corresponding radiation impact indices were calculated. For the long term period after the accident radiation safety standards for man are shown to ensure radiation safety for biota as well. At the same time in the early period after the accident the emergency regulations do not guarantee adequate protection of nature, some species of which can be subject to irradiation more than man, even if countermeasures like evacuation are not applied. A conclusion has been made on the necessity of a more detailed and comprehensive analysis of situations when the anthropocentric principle "if radiation standards protect man then biota are also adequately protected" is violated.     

Radiobiology and the lessons of Chernobyl

The Chernobyl accident has marked the beginning of a new stage of radiobiology development and revealed scantiness of old concepts. One should (1) search for effective protectors against the long-term influence of low-level radiation and means of removal of radionuclides using criteria that differ principally from those used previously in selecting among nontoxic antioxidants, immunomodulators, and adaptogens; (2) study systematically the synergism of low doses of harmful agents and review the hygienic standardization system with due regard for the risk from their combinations; (3) consider comprehensively, on the basis of the experimental and clinical experience, the problem of "hot" particles and remote consequences of their influence on the respiratory and digestive systems; (4) study independently the problem of chronic stress as a combination of radiation effects and psycho-emotional consequences of the accident and living in the exposed areas; (5) consider it inadmissible to include in the B category the population of the districts influenced by the accident and to use the concept: "35 rads during the lifetime" in standardizing the radiation load; (6) organize a comprehensive analysis of the Chernobyl accident consequences for public health within the contaminated areas as well as for animals and plants using a single approved methodology and programme, the principle of "other equal conditions" being provided.