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Frequent natural killer cell abnormality in children in an area highly contaminated by the Chernobyl accident.

Since January 1991, we have been performing thyroid surveys and hematologic and immunologic screening on children in Chechersk, Belarus, a city situated in one of the areas most seriously contaminated with high levels of radionuclides after the Chernobyl accident. Ten children selected from 713 children because of goiter did not show a decrease in humoral immunity or in the number and function of T cells. By contrast, natural killer (NK) cell activity against K562 cells was depressed in 4 of these 10 children. The clinical and laboratory findings indicated that previously reported diseases with NK cell dysfunction could be excluded. A comparative analysis of NK cell activity in children from areas with and without high 137Cs levels revealed a high frequency of abnormal NK cell activity only in children from the area contaminated by radioactive fallout. In addition, there was no correlation between NK cell activity and NK cell number as percentage in the children from the area with high 137Cs levels. Neither activity nor number of NK cells was correlated with the body content of 137Cs. Thus, the frequent abnormality of NK cell function may not have been due to actual internal exposure to the long-lived radionuclide.

Adolescent↗

Thyroid cancer in children in Belarus after Chernobyl.

The accident to the nuclear reactor at Chernobyl in the Ukraine in April 1986 led to the exposure of substantial populations in northern Ukraine and southern Belarus to radioactive fallout. Recently increases in the incidence of childhood thyroid cancer have been reported from these areas. The possible causal association between exposure to the isotopes of iodine in the fallout and the increased thyroid cancer is examined, with a view to predicting the public health consequences of this aspect of the accident. The reported increases are shown to be consistent with a causal association and, if this is established, then a substantial increase in thyroid cancer can be expected over the next 50 years in the exposed populations. This conclusion underlines the urgent need for research to establish beyond doubt the origin of the reported increases and to formulate an appropriate public health response, including exploration of possible mitigating measures for the future.

Accidents↗

Microsatellite instability and loss of heterozygosity in radiation-associated thyroid carcinomas of Belarussian children and adults.

DNA from 129 paired thyroid tumorous and non-tumorous tissue samples of Belarussian children (102 patients; age at surgery </=18 years) and adults (27 patients; age at surgery 19-35 years), who had been exposed to radioactive fallout from the Chernobyl reactor accident in 1986, was examined for microsatellite instability (MSI) and loss of heterozygosity (LOH). Twenty-eight microsatellite markers were chosen because of their vicinity to DNA repair genes or genes involved in tumorigenesis as well as regions of chromosomal breakpoints in thyroid tumours. In 40 patients (31% of 129) we detected a total of 73 alterations, 80% of which were classified as LOH and only 20% as MSI. Amongst these 40 patients we identified a subgroup of 11, mainly young female patients (8.5% of 129), exhibiting alterations in at least two microsatellite markers. For comparison we examined samples from spontaneous thyroid carcinomas without radiation history from 20 adult patients from Munich (mean age at surgery 56 +/- 13 years). None of the tumour samples investigated showed evidence of alterations in the 28 microsatellite markers tested. Taken together our data indicate an increased instability of microsatellite markers in thyroid cancers from Belarussian patients. At present, it is uncertain whether the increased genome instability observed in Belarussian patients is the result of the exposure to radioactive iodine from the Chernobyl reactor accident or due to the young age of the patients.

Adolescent↗

Radionuclide contamination of foods imported into Iraq following the Chernobyl nuclear reactor accident.

Since early 1986, a monitoring program for radionuclides in imported foods has been carried out by the Iraqi Atomic Energy Commission. After the Chernobyl nuclear reactor accident in the Soviet Union, the program was expanded; our laboratory was officially designated by the Iraqi Government to measure radionuclide activity concentrations in foodstuff imported from countries known to be severely contaminated by Chernobyl radioactive fallout. Gamma-spectrometric analysis was used. Food items such as powdered milk, lamb meat, poultry, cereals and grains imported into Iraq before the Chernobyl accident did not contain any detectable fission products. However, all lamb meat, 81% of the lentil, 44% of the powdered milk and chick-pea, and 17% of the roast beef samples were contaminated with 137Cs or 134Cs and 137Cs. The highest 137Cs contamination levels found were 82, 147, 420, 6 and 4 Bq kg-1, respectively. Contamination by 134Cs was approximately 50% of the values given above.

Accidents↗

The psychological consequences of the Chernobyl accident--findings from the International Atomic Energy Agency Study.

In October 1989, more than 3 years after the nuclear power plant accident at Chernobyl, in the Ukraine, the Government of the Union of Soviet Socialist Republics requested that the International Atomic Energy Agency (IAEA) evaluate the medical and psychological health of residents living in areas identified as being contaminated with radioactive fallout. The IAEA designed and conducted a collaborative study to examine whether there were any measurable effects of exposure to the low levels of ionizing radiation resulting from the accident. The study, using structured interviews and IAEA laboratory equipment, collected data on more than 1,350 residents of 13 villages. IAEA clinical staff members concluded that they could not identify any health disorders in either the contaminated or nearby (uncontaminated) control villages that could be attributed directly to radiation exposure. The clinical staff, however, did note that the levels of anxiety and stress of the villagers appeared to be disproportionate to the biological significance of the levels of IAEA-measured radio-active contamination. Almost half the adults in all the villages were unsure if they had a radiation-related illness. More than 70 percent of persons in the contaminated villages wanted to move away, and approximately 83 percent believed that the government should relocate them. The IAEA effort indicates that the villagers need to be educated about their actual risks, and they need to understand what types of illnesses are, and are not, associated with exposure to radioactive contamination. Unfortunately, the villagers' needs may exceed the available resources of their local and central governments.

Accidents↗

[The perception of the radiation situation and assessment of their own health status by the population living in an area under strict radiation control].

Studies of subjective perception of the radiation situation, self-estimation of the health status by the population, the attitude of the population to the formal information available were carried out in the strong radiation control areas and in the regions not polluted by radioactive fallout. Before the accident 71.6% of the population were not aware of real danger of radiation for health. During the accident and after it, mass media were the main source of information on the consequences of the accident and the effect of radiation (71.1%). 38% of the information was provided by scientists and specialists. 89.6% of the persons interviewed experience anxiety whatever the intelligence available. Only 13.4% of those who live in the areas polluted by radionuclides feel well. The low self-estimation of the health status, the high level of anxiety together with the deficiency of radiation and hygienic intelligence favour the forcing of the social and psychological tension and reduce the effectiveness of the whole complex of measures carried out in the areas polluted with radionuclides.

Accidents↗

Systematic ultrasound screening as a significant tool for early detection of thyroid carcinoma in Belarus.

We report the results of ultrasound screening of the thyroid gland in 3,051 Belarus children 4-14 years of age exposed to radioactive fallout due to the Chernobyl accident. Screening was performed in 1990, 1993 and 1998. The study demonstrated that with time the prevalence of thyroid nodules in this contaminated region increased from 1.2% to 3.5%, mostly due to pathologically verified nodular goiter and non-verified small solid nodules and cysts. In contrast, the prevalence of thyroid carcinoma decreased from 0.6% in 1990 to 0.3% in 1993. We found 15 patients with carcinoma. On analysis of the ultrasound pattern of all carcinomas, we observed nodular and diffuse variants. Thus, we can conclude that systematic ultrasound screening is useful for the early detection of thyroid carcinoma in the population of Belarus exposed to radiation due to the Chernobyl accident.

Adolescent↗

Birth prevalence of congenital malformations in Bavaria, Germany, after the Chernobyl accident.

This study considers whether or not exposure to radioactive fallout from the Chernobyl accident led to an increased prevalence of congenital malformations in infants born in Bavaria, the German state with the highest levels of contamination after the accident. The odds ratios for major malformations after the accident relative to before were used as indicators for adverse health effects. Since measurements of caesium in soil showed that contamination was considerably higher in Southern Bavaria than in Northern Bavaria, the odds ratios were calculated for both regions separately. Analysis did not show a significant increase in any of the odds ratios of the selected malformations in Southern Bavaria as compared to Northern Bavaria. Consequently, this study provides no evidence that radiation from Chernobyl caused an increase in the birth prevalence of major congenital malformations.

Abnormalities, Radiation-Induced↗

High prevalence of RET rearrangement in thyroid tumors of children from Belarus after the Chernobyl reactor accident.

RET rearrangement was studied in papillary thyroid carcinomas (PTC) of children exposed to radioactive fallout in Belarus after the Chernobyl accident. To detect RET rearrangement in small tissue samples from thyroidectomy specimen (12 PTC of children; 2 PTC and 1 follicular carcinoma of adults; non-tumorous thyroid tissue of 4 children and 4 adults as controls), a RT-multiplex PCR was developed using primers suited to amplify fragments in different quantities depending on the presence or absence of RET rearrangements in the tissues. The type of rearrangement was determined by RT-PCR and direct sequencing using primers for ret/PTC1, 2 and 3. Two-thirds of the papillary thyroid carcinomas of the children revealed a RET rearrangement, with ret/PTC3 being more frequent by a factor of 3 than ret/PTC1. ret/PTC2 was not detected. All RET rearrangement-positive tumors had lymph node metastasis while half of the tumors with wild-type cRET had not. More than half of the cases with ret/PTC3 expressed not only the ELE/RET transcript as expected, but also the RET/ELE transcript. Intrachromosomal rearrangement involving RET and the adjacent H4 or ELE gene on chromosome no. 10 is a very frequent event in thyroid cancer of children of the Chernobyl-contaminated zone of Belarus.

Adult↗

Detection of a novel type of RET rearrangement (PTC5) in thyroid carcinomas after Chernobyl and analysis of the involved RET-fused gene RFG5.

A novel type of RET rearrangement, PTC5, was detected in papillary thyroid carcinomas of two patients exposed to radioactive fallout after Chernobyl. Reverse transcription-PCR and rapid amplification of 5'-cDNA ends revealed a fusion of the ret tyrosine kinase (TK) domain with a sequence identical to that described previously as ret-II. Ret-II is a transfection artifact in NIH3T3 cells and has not yet been detected in any human tumor. Overlapping sequences found in the expressed sequence tag databases enabled us to sequence the COOH terminus of the ret-fused gene 5 (RFG5). The combined data made it possible to assemble a full-length rfg5 protein sequence. Computer-assisted analysis of this sequence reveals four putative coiled-coil structures, possibly involved in dimerization, but no membrane-binding sequences. Northern blots show a ubiquitous RFG5 expression in various normal tissues, including the thyroid gland. In addition to the RFG5/RET, we also detected the reciprocal RET/RFG5 transcript in both tumor samples, suggesting that the rearrangement is based on a balanced reciprocal translocation. In agreement with other rearranged TKs, it is concluded that the transforming action of the new fusion protein rfg5/ret in thyroid tumors may be due to an activation of the ret TK by constitutive expression and dimerization potential of the 5'-fused rfg5 protein. Ret immunohistochemistry indicates that the fusion protein is expressed in all cells of PTC5 tumors, suggesting that RFG5/RET rearrangement is an early event in thyroid carcinogenesis.

Adult↗

Thyroid consequences of the Chernobyl nuclear accident.

It is well recognized that the use of external irradiation of the head and neck to treat patients with various non-thyroid disorders increases their risk of developing papillary thyroid carcinoma years after radiation exposure. An increased risk of thyroid cancer has also been reported in survivors of the atomic bombs in Japan, as well as in Marshall Island residents exposed to radiation during the testing of hydrogen bombs. More recently, exposure to radioactive fallout as a result of the Chernobyl nuclear reactor accident has clearly caused an enormous increase in the incidence of childhood thyroid carcinoma in Belarus, Ukraine, and, to a lesser extent, in the Russian Federation, starting in 1990. When clinical and epidemiological features of thyroid carcinomas diagnosed in Belarus after the Chernobyl accident are compared with those of naturally occurring thyroid carcinomas in patients of the same age group in Italy and France, it becomes apparent that the post-Chernobyl thyroid carcinomas were much less influenced by gender, virtually always papillary (solid and follicular variants), more aggressive at presentation and more frequently associated with thyroid autoimmunity. Gene mutations involving the RET proto-oncogene, and less frequently TRK, have been shown to be causative events specific for papillary cancer. RET activation was found in nearly 70% of the patients who developed papillary thyroid carcinomas following the Chernobyl accident. In addition to thyroid cancer, radiation-induced thyroid diseases include benign thyroid nodules, hypothyroidism and autoimmune thyroiditis, with or without thyroid insufficiency, as observed in populations after environmental exposure to radioisotopes of iodine and in the survivors of atomic bomb explosions. On this basis, the authors evaluated thyroid autoimmune phenomena in normal children exposed to radiation after the Chernobyl accident. The results demonstrated an increased prevalence of circulating thyroid antibodies not associated with significant thyroid dysfunction. This finding is consistent with the short period of follow-up, but it is highly likely that these children will develop clinical thyroid autoimmune diseases in the future. Therefore, screening programmes for this at-risk population should focus, not only on the detection of thyroid nodules and cancer, but also on the development of thyroid autoimmune diseases.

Autoimmunity↗

Post-Chernobyl thyroid carcinoma in Belarus children and adolescents: comparison with naturally occurring thyroid carcinoma in Italy and France.

After the Chernobyl nuclear accident (April 26, 1986), childhood thyroid carcinoma had a great increase in Belarus and Ukraine, as a consequence of the exposure to iodine radioactive fallout. The epidemiological and clinical features of the disease were studied in 472 patients less than 21 yr old at diagnosis, with differentiated thyroid carcinoma, representing 97.7% of all thyroid carcinomas diagnosed in Belarus between May, 1986, and December, 1995. The results were compared with those of 369 subjects of the same age group, with naturally occurring thyroid carcinoma, observed in Italy and France. Between 1986 and 1989, the number of thyroid cancer cases per year ranged from 3-8 and increased to 31 in 1990, to 66 in 1991, to 72 in 1992, to 93 in 1993, to 96 in 1994, and to 90 in 1995. The age at diagnosis was 14 yr or less in 78.8% (children group) and more than 14, but less than 21, yr in the remaining subjects (adolescents group). Mean (+/- SD) age at the time of the accident was 4.4 +/- 3.4 yr (3.2 +/- 2.3 in children and 8.9 +/- 2.7 in adolescents), the majority of the patients (62.9%) being 5 yr old or less. The time interval between the accident and the diagnosis (latency period) decreased progressively from 7.5 +/- 1.6 yr in children 0-2 yr old at the time of the accident to 6.0 +/- 1.6 yr in those 9-11 yr old. Since 1993, the yearly distribution of new cases showed a decrease in the subjects 9 yr old or more at the time of the accident but not in those 5 yr old or less. This could not be accounted for by a shift of exposed subjects to an age group at diagnosis not included in this study, because only subjects less than 12 yr of age at the time of the accident were considered in this analysis. Mean age at diagnosis in Belarus patients was 11.3 +/- 3.1 yr (10.1 +/- 2.3 in children and 15.7 +/- 1.4 in adolescents), whereas, among patients with naturally-occurring thyroid carcinomas from Italy and France, the majority of cases were diagnosed after 14 yr of age (mean age at diagnosis: 14.6 +/- 4.2 yr). The female-to-male ratio was significantly higher in Italy and France (2.5/1), compared with the ratio of patients from Belarus (1.6/1). Most of the tumors were papillary in both series, but a relatively high proportion of follicular carcinomas (P = 0.0001) was found in Italy/France (15.2%), as opposed to 5.3% in Belarus. Extrathyroidal extension and lymph node metastases were more frequent in Belarus (49.1%, P = 0.0001; and 64.6%, P = 0.002, respectively) with respect to Italy/France (24.9% and 53.9%, respectively). Thyroid lymphocytic infiltration and circulating antithyroperoxidase antibody were more frequent in Belarus patients. Our analysis of Belarus thyroid cancer patients less than 21 yr old showed that the post-Chernobyl increase in thyroid carcinomas involved both children and, to a much lesser extent, adolescents. Subjects 5 yr old or less at the time of the accident accounted for the majority of the patients. No evidence of a decrease in the number of new cases was observed in this age group, as opposed to older subjects. These data support the concept that subjects who were younger at the time of radiation exposure had, and continue to have, a greater risk of developing thyroid carcinoma and strongly suggest that this age group should be carefully monitored in the future. When compared with naturally occurring thyroid carcinoma of the same age group observed in Italy and France, the post-Chernobyl Belarus thyroid carcinomas affected younger subjects, were less influenced by gender, were virtually always papillary, had a greater aggressiveness at presentation, and were more frequently associated with thyroid autoimmunity.

Adenocarcinoma, Follicular↗

Health impacts of large releases of radionuclides. The fate and impact of radiocontaminants in urban areas.

The Chernobyl accident made it clear that the contaminants released after a severe nuclear accident may spread over large areas, and thereby form a significant external radiation hazard in areas of high population density. Since then, the weathering effects on the deposited radiocontaminants (essentially radiocaesium) have been followed on different types of surface in urban, suburban and industrial areas in order to enable an estimation of the long-term impact of such events. Analytical expressions have been derived for the typical behaviour of radiocaesium on the different surfaces, and dose measurements and calculations for different urban environments have pinpointed which surfaces generally contribute most to the dose and consequently are most important to clean. At this point, after nearly a decade, the dose rate from horizontal pavements has decreased by at least a factor of 10, whereas the dose rate from an area of soil or a roof has generally only been halved. The contamination on walls is the most persistent: it has only decreased by 10-20%.

Cesium Radioisotopes↗

Incidence pattern of thyroid cancer in Norway: influence of birth cohort and time period.

The incidence of thyroid cancer in Norway increased about 2-fold for both sexes during the period 1955 to 1989 (4691 cases). In the last 5-year period, however, a decline was observed, especially among females. The ratio between age-adjusted incidence rates in Northern Norway compared with Southern Norway was 1.6 for females and 1.5 for males, and the incidence pattern during the period was similar in the 2 regions. The analysis of age-cohort-period models showed a strong cohort effect in both sexes. The reason for this is not clear, although radiation treatment during childhood and dietary habits may possibly be involved. A weaker but statistically significant and transient period effect was also present, giving relatively higher incidence rates, especially in the 1970s. Although this result may be consistent with an influence of radioactive fallout in the northern area, more detailed studies are needed.

Adolescent↗

Changes in registered congenital anomalies in the Republic of Belarus after the Chernobyl accident.

A descriptive analysis of birth defects and malformations was performed to assess whether the rates of these defects correlate with the geographic areas of Belarus that received different levels of 137Cs contamination resulting from the Chernobyl catastrophe. Since this accident in 1986, the frequency of both congenital and fetal abnormalities in the Republic of Belarus has apparently increased. This increase is most prominent in areas with at least 555 9Bq/m2 radioactive contamination, although it has not been possible to correlate the individual dose received by a pregnant woman with the incidence of congenital malformations. The types of anomalies that were most increased in frequency were multiple congenital malformations, polydactyly, and reduction limb defects. These malformations are commonly associated with dominant new mutations. Chromosomal disorders such as occur in Down syndrome were not increased in frequency, nor could teratogenic effects be attributed to exposure to ionizing radiation. Preventive measures have apparently reduced the number of births with congenital abnormalities but have had no apparent effect on the frequency of fetal defects. Results of our analysis are consistent with the hypothesis that ionizing radiation released during the Chernobyl accident may have placed fetuses and neonates at risk for congenital malformations. Epidemiological studies are now required to determine whether a mother's radiation dose correlates with congenital malformations in her children.

Abnormalities, Radiation-Induced↗

131I dose-dependent thyroid autoimmune disorders in children living around Chernobyl.

We assessed the major lymphocyte subsets in the peripheral blood, thyroid ultrasonography, levels of serum autoantibodies to thyroglobulin (AbTg), thyroid hormones, and thyroid-stimulating hormone (TSH) in 53 children without any chronic diseases living continuously around Chernobyl. The subjects ranged in age from 7 to 14 years and had different doses of 131I to their thyroid. Healthy children living on noncontaminated areas were assessed as controls. The majority of children with doses of 131I had normal levels of thyroid hormones. However, the percentages of positive sera for AbTg, TSH levels, ultrasonographic thyroid abnormalities, and abnormal echogenicity were significantly higher in children with doses of 131I than in controls. The dose of 131I to thyroid correlated positively with serum AbTg levels, percentage of CD3+CD4+ cells, and CD3+CD4+/CD3+CD8+ cell ratio and negatively with number of CD3+CD8+ and CD3-/CD16, CD56+ cells. Thus, our study demonstrates an association between dose of 131I and autoimmune thyroid disorders in this population of children.

Adolescent↗