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[The rehabilitation under alpine conditions of the participants in the cleanup of the accident at the Chernobyl Atomic Electric Power Station who are ill with chronic bronchitis].

24 patients exposed to low-dose radiation after the Chernobyl accident were examined before and after 24-day treatment of chronic bronchitis in the high-altitude rehabilitation center (3200 m above the sea level) in Tien Shan. Sanogenic alpine climate improved the patients' general condition, physical performance and lung ventilation, corrected compromised immunity. After high-altitude adaptation tracheobronchial inflammation alleviated, cytologic composition and surface activity of bronchoalveolar fluid returned to normal. Therefore, high-altitude treatment of Chernobyl accident victims with chronic bronchitis is effective and can be recommended for such patients.

Adaptation, Physiological↗

Prevalence of mutations of ras and p53 in benign and malignant thyroid tumors from children exposed to radiation after the Chernobyl nuclear accident.

Starting 4 years after the Chernobyl accident, a dramatic increase in incidence of thyroid carcinoma was noticed in children from contaminated areas. The incidence of benign thyroid lesions in the exposed population was also increased. To study the possible role of ras and p53 genes in radiation-induced thyroid tumorigenesis, 33 papillary carcinomas, one follicular carcinoma and 22 benign lesions removed from children aged 5-19 were screened for point mutations of H-, K-, and N-ras, as well as of p53 (exons 5-8) using single strand conformation polymorphism (SSCP) analysis. Ras point mutations were detected in 1/1 case of follicular carcinoma (N-ras codon 61 CAAgln-->AAAlys), and in 3/7 follicular adenomas (N-ras codon 61 CAAgln-->CGAarg x 2, CAAgln-->AAAlys). None of the cases of papillary thyroid carcinoma was positive for ras oncogene abnormalities. The lack of K-ras mutations was confirmed by allele-specific oligonucleotide hybridization (ASOH), and by sequencing in five cases. Somatic point mutations in p53 were found by SSCP in 2/33 papillary thyroid carcinomas, with one missense mutation (exon 5, codon 160 ATGmet-->GTGval) and another silent mutation (codon 182, TGCcys-->TGTcys). Immunohisto-chemically, focally positive p53 staining was found in four papillary carcinomas being primarily confined to solid and poorly-differentiated areas in tumors. These data demonstrate that as opposed to the few reports on tumors arising after therapeutic external irradiation, ras mutations are not primary events in the development of post-Chernobyl thyroid papillary carcinomas. p53 mutations do not appear to be important in the development of these tumors, but may in some cases have a role in progression to a more aggressive phenotype that has not yet fully manifested in these pediatric neoplasms.

Adolescent↗

Molecular and biochemical analysis of RET/PTC4, a novel oncogenic rearrangement between RET and ELE1 genes, in a post-Chernobyl papillary thyroid cancer.

A post-Chernobyl papillary thyroid cancer, displaying a novel ELE1/RET oncogenic rearrangement with an anomalous fusion transcript, was molecularly characterized. In spite of the presence of a normal breakpoint in exon 5 of the activating ELE1 gene, the sequence of the rearranged genomic DNA showed a previously unreported intra-exonic breakpoint in the RET protooncogene. As a consequence, a cDNA sequence 93 nucleotides larger than the regular one, and with the exon 5 of ELE1 joined to exon 11 instead of exon 12 of RET, is formed. To characterize the product of this new oncogenic ELE1/RET rearrangement, here designated as RET/PTC4, we performed an immunoprecipitation and Western blot analysis on cell extracts from NIH3T3 transfectants. The results showed the presence of two isoforms of the chimeric protein, displaying a constitutive tyrosine phosphorylation. As expected, the molecular weight of this protein was higher than that of RET/ PTC3 protein (p80 and p85, instead of p76 and p81). Previous reports, from our and other laboratories, showed that post-Chernobyl papillary thyroid carcinomas are characterized by a high frequency (about 60%) of RET oncogenic rearrangements (Fugazzola et al., 1995; Klugbauer et al., 1995; Ito et al., 1994). These events predominantly involve ELE1 activating sequence, thus producing RET/PTC3 oncogene (Fugazzola et al., 1995; Klugbauer et al., 1995). Hence, this elevated frequency of RET rearrangements could increase the probability of selecting unusual events as that here described. Alternatively, targeted radiation effects could be responsible for the atypical RET rearrangement producing RET/PTC4 oncogene.

Base Sequence↗

A new form of RET rearrangement in thyroid carcinomas of children after the Chernobyl reactor accident.

Intrachromosomal rearrangements involving the RET and the adjacent H4 or ELE1 gene are very frequent events in thyroid cancer of children from Belarus after the Chernobyl reactor accident (Klugbauer et al., 1995). The fusion product between ELE1 and RET (RET/ PTC3) seems to be the prevailing type of rearrangement as shown in a recently published study using a novel RT multiplex PCR approach in combination with the identification of the rearrangement type by RT-PCR and direct sequencing. Now we found a new type of RET rearrangement: By the 5'RACE method we demonstrated in cDNA the fusion of the tyrosine kinase domain of RET with a truncated ELE1 gene shorter than the ELE1 in RET/PTC3. Sequencing of genomic DNA revealed a rearrangement breakpoint at position 41 of a new ELE1 intron (522 bp in length). The new oncogene RET/ delta PTC3 is shortened by one ELE1 exon of 144 bp in length. Structural considerations of the ele1 amino terminal of RET/ delta PTC3 suggest that the transforming activity of the fusion protein is apparently not affected by this truncation. The exon lacking in RET/ delta PTC3 was found to code in the reciprocal transcript RET/ delta ELE1 and increased its size by 144 bp. Obviously the new and possibly additional ELE/RET fusion molecules might even increase the high prevalence of ELE1/RET rearrangements in thyroid carcinomas of children after the Chernobyl reactor accident.

Amino Acid Sequence↗

The Chernobyl accident and radiation risks: dynamics of epidemiological rates (morbidity, disability and death rates) according to the data in the national registry.

Ten years have elapsed since the Chernobyl accident. The gravest technologically generated accident throughout human history has attracted considerable attention from the whole world community. At the same time, the problem of estimating the total damage to life and health of people exposed to radiation remains very complicated. The negative effects of Chernobyl include a spectrum of factors which may reinforce each other. In particular, to date there are no theoretical models or practical recommendations on estimating the contribution of the social, psychological or emotional factors that surround diseases due to radiation accidents. On the other hand, for maximum effective rehabilitation of the affected population, the impartial determination of the contribution by both radiation and non-radiation components is necessary. Therefore, the continuation of long-standing investigations within the framework of the National and Radiation and Epidemiological Registry along with obtaining new scientific data in the field of radiation epidemiology is of great practical importance in limiting the health consequences of the accident.

Adolescent↗

Dosimetric support of the International Programme on the Health Effects of the Chernobyl Accident (IPHECA) pilot project: main results and problems.

The problem of post-Chernobyl dosimetry is unique in its complexity in the history of radiation medicine and radiation protection. This is because the early experience of mass exposure of people (bombing of Hiroshima and Nagasaki, Windscale and South-Ural accidents, exposure of inhabitants of Nevada in the United States of America, the Semipalatinsk area in the former USSR, the Marshall Islands, and the Goiånia accident in Brazil, and others) differed both in the much simpler structure of the irradiation source and in the number and characteristics of exposed persons. It is obvious that post-Chernobyl dosimetry, both as an independent problem, and as a tool for epidemiological studies, requires significant expertise and economic and technical expenditures. Extensive and deep research has been carried out in Ukraine for the past 10 years. This article reviews the main results of these studies.

Adolescent↗

[The results of medical and dosimetric research on the population and on those who worked in cleanup subjected to radiation exposure as a result of the Chernobyl catastrophe].

The Russian State Medical and Dosimetric Register (RSMDR) of subjects exposed to radiation due to the Chernobyl accident and a radiation epidemiological analysis of the data collected are described. At present, RSMDR covers 435,000 persons including 152,000 participants in the liquidation of the accident consequences (liquidators). Predictive estimates (based of the models recommended by the International Commission of Radiation Protection) and the actual data obtained 9 years after the accident are compared. It has been found that within 20 years after radiation in a cohort of liquidators an attributive risk for leukemia and for solid cancers will be 23.6 and 2.8%, respectively. The actual data after 10 years correspond with the predictive estimates. According to disability and morbidity rates, the 1986-1987 liquidators represent a high-risk group. Radiation epidemiological examinations for thyroid cancer in children (at the moment of the Chernobyl accident) were made in the Bryansk and Kaluga Regions. The relative risk for detected cancers was ascertained to be 7.15. This signifies that about 90% of the thyroid cancers detected are caused by a radiation factor.

Air Pollution, Radioactive↗

Lungs exposed to nuclear catastrophe: one-year therapeutic programme in Chernobyl liquidators group.

The high prevalence of chronic respiratory problems in cleaning technicians (so-called "liquidators") of the destroyed reactor at Chernobyl and prolonged persistence of inhaled radioactive particles in their lungs suggested a substantial link between radioactive exposure and the diseases observed. Taking into account the importance of the problem, we started this study with the aim of establishing an effective and useful therapeutic program and assessing its efficacy during a one-year period of treatment. Chernobyl liquidators (n = 20) were screened by clinical history, physical examination, lung function test, chest radiograph, electrocardiogram, complete blood cell counts, serum chemistry, immunological blood tests, and complete BAL fluid investigation. One group of the patients (n = 10) underwent a special one-year treatment including polyvitamins, N-acetylcysteine, and therapeutic BAL every 3 months. The technique of therapeutic BAL has proven to be a promising and effective tool in the treatment of lung diseases induced by inhalation of radioactive particles.

Adult↗

The Estonian study of Chernobyl cleanup workers: II. Incidence of cancer and mortality.

A cohort of 4,742 men from Estonia who had participated in the cleanup activities in the Chernobyl area sometime between 1986 and 1991 and were followed through 1993 was analyzed with respect to the incidence of cancer and mortality. Incidence and mortality in the cleanup workers were assessed relative to national rates. No increases were found in all cancers (25 incident cases compared to 26.5 expected) or in leukemia (no cases observed, 1.0 expected). Incidence did not differ statistically significantly from expectation for any individual cancer site or type, though lung cancer and non-Hodgkin's lymphoma both occurred slightly more often than expected. A total of 144 deaths were observed [standardized mortality ratio (SMR) = 0.98; 95% confidence interval (CI) = 0.82-1.14] during an average of 6.5 years of follow-up. Twenty-eight deaths (19.4%) were suicides (SMR = 1.52; 95% CI = 1.01-2.19). Exposure to ionizing radiation while at Chernobyl has not caused a detectable increase in the incidence of cancer among cleanup workers from Estonia. At least for the short follow-up period, diseases directly attributable to radiation appear to be of relatively minor importance when compared with the substantial excess of deaths due to suicide.

Estonia↗

[The morphological characteristics of craniocerebral and cerebrospinal hernias in children after the accident at the Chernobyl Atomic Electric Power Station].

In the post-Chernobyl period of time the quantity of children operated for congenital cerebral and cerebrospinal hernia has been increased almost by two times. The signs of degeneration were not observed while morphological study of hernial sac wall in 96 children operated on from 1981 till 1986 year. Of 167 children operated on after the Chernobyl accident (1986-1992 yrs) in 10 (5.9%) of them the degeneration of substantia medullaris astrocytes was observed.

Brain↗

Absence of G(s)alpha gene mutations in childhood thyroid tumors after Chernobyl in contrast to sporadic adult thyroid neoplasia.

Heterotrimeric G proteins participate in the signal transduction cascade. Adult thyroid tumors have been shown to harbor specific point mutations in codons 201 and 227 of the G(s)alpha subunit of the adenylate cyclase stimulator. This protein affects the GDP/GTP turnover and finally results in an enhanced activation of G(s) and thus adenylate cyclase. We attempted to find out if G(s)alpha gene mutations were present in thyroid tumors of children from Belarus after the Chernobyl nuclear accident. Paraffin sections of 20 thyroid tumors were used for PCR amplification by oligonucleotide intron primers flanking exons 8 and 9, encompassing codon 201 and 227, respectively. By direct sequencing of the 274-bp amplification product, we did not detect any mutations of the G(s)alpha gene in codon 201 or 227. In contrast to thyroid neoplasia of adults, G(s)alpha gene mutations do not play a role in the development of childhood thyroid tumors after the Chernobyl reactor accident.

Carcinoma, Papillary↗

Thyroid pathology in residents of the Kiev region, Ukraine, during pre- and post-Chernobyl periods.

We compared the results of thyroid surgery in residents of the Kiev region in the Ukraine during the 4 years preceding the 1986 Chernobyl nuclear power station (CNPS) accident with the results during the 8 years following the catastrophe. We examined 16,340 thyroid glands, removed from patients during the periods 1982 to 1986 and 1987 to 1995, and found increases in the rates of Hashimoto's disease, follicular adenoma, and thyroid cancer. The increased incidence of papillary microcarcinoma deserves special attention when compared to the rates of clinically manifested forms of thyroid cancer. The resulting data bear evidence to the effect of the environment on the thyroid diseases following the Chernobyl catastrophe. However, the role of certain subjective factors must also be considered.

Adenoma↗

[A micronucleus analysis of the peripheral blood lymphocytes of the professional contingent and of the self-settlers in the exclusion zone of the Chernobyl Atomic Electric Power Station].

The chromosomal damage (micronuclei) of the peripheral blood lymphocytes of the group of professionals who had participated in the liquidation of the Chernobyl NPP accident and have continued their work at the "Shelter" and of the group of self-settlers who living for about ten year in the Chernobyl NPP alienation zone were studied. Residents of Kyïv were the group for comparison. It was found that in professionals the number of micronuclei was higher due to the presence of cells with several micronuclei while in the self-settlers it was due to the increase in the number of cells with one micronucleus. Also was determined the correlation between the frequency of micronuclei in the lymphocytes of the self-settlers on the one hand and the level of radionuclides contamination of territory and dose loading on the other.

Adult↗

[The dynamic indices of the natural cell-mediated cytotoxicity in patients with duodenal peptic ulcer who participated in the cleanup of the aftermath of the accident at the Chernobyl Atomic Electric Power Station].

As many as 129 patients with duodenal ulcer (DU) who took part in the elimination of the aftereffects of the Chernobyl Nuclear Power Plant breakdown were studied for parameters characterizing the natural cell-mediated cytotoxicity, such as ability to form conjugates with NK-sensitive K-562 target cells, content of conjugate-forming mononuclear cells endowed with known lytic activity, total cytotoxic activity. The functional state of NK-cells is shown to be interrelated with the objective clinical criteria of the condition. Based on the results obtained it can be concluded that alterations in the mechanisms of functioning of NK-cells in the above contingent of examinees can be interpreted as a negative factor in the course of the reparative processes in DU in the remote future after the Chernobyl accident.

Blood Donors↗

[Blood vitamin levels in various population groups in the Ukraine suffering from sequelae to the accident at the Chernobyl power plant].

The levels of vitamins in the blood of persons who suffered from the catastrophe at Chernobyl NPP subject to medically treatment at Kiev clinics at different time periods have been studied. Polyhypovitaminosis has been detected in all the patients groups examined, especially in persons with the diagnosis of acute radiation sickness. The hypovitaminosis status in the organism is regulated by means of an adequate vitamin therapy. The scientifically substantiated vitamin therapy and vitamin prophylaxis are proposed to be performed for the population of Ukraine affected by the consequences of the Chernobyl catastrophe.

Environmental Health↗

[Unstable chromosome aberrations in lymphocytes of liquidators of the Chernobyl accident consequences].

AIM: Analysis of peripheral blood lymphocytes for detecting unstable chromosome aberrations in liquidators of the Chernobyl disaster consequences and in residents of territories contaminated after the accident. MATERIALS AND METHODS: Peripheral blood lymphocytes were tested for unstable chromosome aberrations in 216 subjects who worked for different periods after the Chernobyl accident in 1986-1987 in the 30-km zone and at adjacent territories. The results were correlated to the duration of stay in the zone, terms of examination after the work, exposure dose fixed in the files, deviations in the health status and blood values, and with similar data on 21 residents of the stringent control regions of the Gomel district and 265 patients with different hematological diseases and donor blood samples exposed in vitro. RESULTS: Chromosome aberrations detected in the examined group are represented by dicentrics, paired and nonpaired fragments, acentric rings, and gaps. CONCLUSION: Although not everything is yet clear, we consider that detection of unstable chromosome aberrations of the dicentric type in lymphocytes of subjects who participated in liquidation of the accident consequences in remote periods after exposure persuasively proves that a radiation exposure, no matter what its dose was, took place, and hence, there are good grounds for including the subjects with aberrations in the high risk group. On the other hand, the absence of such aberrations does not rule out the detrimental effect of radiation on the organism.

Cell Culture Techniques↗

[Radioecological sequelae to the accident at Chernobyl power plant for fish].

The estimate of dynamics in concentration of radionuclides in muscles of some game-fish from Kiev reservoir and lakes in Bryansk region for period after Chernobyl accident was carried out. The concentration of 137Cs in fish has not exceeded the admissible concentration (600 Bq/kg ww) since 1993. The exceptions are the cooling-pond of Chernobyl NPP and Kozlanovskoe Lake where the concentration of 137Cs in fish's muscles exceeded the admissible level more than 5-6 times even in 1995. It was concluded that chronic irradiation of game-fish in water bodies outside 30-km zone would not affect the volume of fishing.

Animals↗

[The pathomorphological characteristics of duodenal peptic ulcer in the victims of the accident at the Chernobyl Atomic Electric Power Station: changes in the gastric mucosa].

Gastrobiopsies were studied from patients with duodenal ulcer, 62 of whom took part in the elimination of the effects of the Chernobyl Nuclear Power Plant breakdown, 33 were permanent residents in the territories affected by radioactive contamination, and 36 formed the control group. Several distinguishing features were noted in chronic Helicobacter gastritis in victims of Chernobyl accident versus control, such as higher degree and activity of the inflammatory process spreading over large tissue areas, with Helicobacter pylori being recordable in the gastric mucosa in highly increased numbers, and more frequent occurrence of atrophic changes. Incorporation of radionuclides and external irradiation at dose levels exceeding 25 cause most significant disturbances in regeneration of epithelium, with its enterolyzation and dysplasia going on, which fact makes the risk of neoplastic transformations higher.

Adult↗