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.     

A preliminary assessment of the consequences for inhabitants of the UK of the Chernobyl accident

The accident with the nuclear power reactor at Chernobyl in the USSR resulted in the release of substantial quantities of radioactive material and subsequent increases in radioactivity in the environment in many countries. In this paper the situation in the UK is considered and, from the preliminary monitoring measurements, the major routes of exposure of the population are identified and quantified. For the most part exposures in the UK are within variations in levels of natural background radiation to be found in Europe. An exception is the dose likely to have been received by the thyroids of young people in the north of the UK. From reported measurements of I-131 in milk it is predicted that thyroid doses up to 10-20 times the annual doses received from 'normal' natural background radiation might have affected young children drinking fresh cows' milk. The ways in which this component of exposure could have been reduced and the criteria that govern decisions as to whether or not to implement counter-measures are discussed. The importance of I-131 in milk as a route of exposure of the population to radioactivity is a feature that the Chernobyl accident has in common with the Windscale accident in the UK in 1957, and underlines the importance of milk-producing regions in relation to reactor-sitting policy.     

MnTnBuOE-2-PyP treatment protects from radioactive iodine (I-131) treatment-related side effects in thyroid cancer

Treatment of differentiated thyroid cancer often involves administration of radioactive iodine (I-131) for remnant ablation or adjuvant therapy. However, there is morbidity associated with I-131 therapy, which can result in both acute and chronic complications. Currently, there are no approved radioprotectors that can be used in conjunction with I-131 to reduce complications in thyroid cancer therapy. It is well known that the damaging effects of ionizing radiation are mediated, in part, by the formation of reactive oxygen species (ROS). A potent scavenger of ROS, Mn(III)meso-tetrakis(N–n-butoxyethylpyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP), has radioprotective and anti-tumor effects in various cancer models including head and neck, prostate, and brain tumors exposed to external beam radiation therapy. Female C57BL/6 mice were administered I-131 orally at doses of 0.0085–0.01 mCi/g (3.145 × 105 to 3.7 × 105 Bq) of body weight with or without MnTnBuOE-2-PyP. We measured acute external inflammation, blood cell counts, and collected thyroid tissue and salivary glands for histological examination. We found oral administration of I-131 caused an acute decrease in platelets and white blood cells, caused facial swelling, and loss of thyroid and salivary tissues. However, when MnTnBuOE-2-PyP was given during and after I-131 administration, blood cell counts remained in the normal range, less facial inflammation was observed, and the salivary glands were protected from radiation-induced killing. These data indicate that MnTnBuOE-2-PyP may be a potent radioprotector of salivary glands in thyroid cancer patients receiving I-131 therapy.     

Iodine metabolism and pathologic processes in the thyroid gland under radioiodine lesions in the regions of goitrous endemia

An existing discrepancy between the prognostic estimations and real thyroid gland sickness rate due to radiation exposure from Chernobyl is an evidence of inaccuracy of radiation doses determination. The estimation of the thyroid cancer risks is based on the assumption that the absorbed dose is uniformly distributed in the organ. But functional asynchronicity specific for iodine metabolism in thyroid may modify a space distribution of the dose. The biochemical features of the contaminated areas including iodine deficit and goitrous endemia usually are not taken into account may influence the second phase of thyroid carcinogenesis that is the promotion due to increased accumulation of some carcinogenic microelements in goitrous thyroid. In the work we consider these problems which can make significant changes in radiation risks estimation.     

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.     

Childhood thyroid cancer, radiation dose from Chernobyl, and dose uncertainties in Bryansk Oblast, Russia: a population-based case-control study

A population-based case-control study was conducted to estimate the radiation-related risk of thyroid cancer in persons who were exposed in childhood to (131)I from the Chernobyl accident of April 26, 1986 and to investigate the impact of uncertainties in individual dose estimates. Included were all 66 confirmed cases of primary thyroid cancer diagnosed from April 26, 1986 through September 1998 in residents of Bryansk Oblast, Russia, who were 0-19 years old at the time of the accident, along with two individually matched controls for each case. Thyroid radiation doses, estimated using a semi-empirical model based on environmental contamination data and individual characteristics, ranged from 0.00014 Gy to 2.73 Gy and had large uncertainties (median geometric standard deviation 2.2). The estimated excess relative risk (ERR) associated with radiation exposure, 48.7/Gy, was significantly greater than 0 (P = 0.00013) but had an extremely wide 95% confidence interval (4.8 to 1151/Gy). Adjusting for dose uncertainty nearly tripled the ERR to 138/Gy, although this was likely an overestimate due to limitations in the modeling of dose uncertainties. The radiation-related excess risk observed in this study is quite large, especially if the uncertainty of dose estimation is taken into account, but is not inconsistent with estimates previously reported for risk after (131)I exposure or acute irradiation from external sources.     

Adjuvant I-131 therapy for T0–3 N1b M0 differentiated thyroid cancer with many (≥ 5) positive nodes

BackgroundIn patients with well-differentiated thyroid cancer, there is controversy about the prognostic importance of a large number of positive neck nodes and the potential value of radioiodine therapy. The purpose of this study was to evaluate this issue in the group of patients for whom it is most clinically important — those with classic histology and favorable T and M stage.Materials and methodsTwenty-five patients met the following inclusion criteria: classic histology of papillary or follicular thyroid carcinoma treated with total thyroidectomy and neck dissection followed by adjuvant I-131 treatment in our department between January 1, 2003, and December 31, 2013; adult age of > 21 years; and American Joint Committee on Cancer (AJCC ) stage (8^th edition) of T0–3, N1b with ≥ 5 positive nodes, and M0.ResultsThe median positive node number was 10 (range, 5–31). The median adjuvant I-131 dose was 158 mCi (range, 150–219 mCi). The median follow-up in patients without recurrence after treatment was 7.3 years. The 10-year actuarial rates were favorable: overall survival, 100%; freedom from visible recurrence, 82%; and visible or biochemical recurrence, 72%.ConclusionRecurrence was infrequent in our study population with ≥ 5 positive nodes following moderate-dose adjuvant I-131 treatment. These results are valuable in directing initial adjuvant therapy and follow-up intensity. Our results do not inform the question of the use of postoperative thyroglobulin (Tg) level to select N1b patients for low-dose I-131 treatment.     

Radioiodine: Biokinetics,mean dose and dose distribution

Summary For the radioiodine isotopes I-123, I-125, I-131, and I-132 the mean tissue dose and local dose distribution in the epithelial cells of a follicle have been calculated and compared to each other. Moreover, dose factors have been estimated for I-131 as a function of age considering age-dependent ingestion (milk consumption) and inhalation rates. Thereby, besides age-dependent biological half-times and thyroid masses, the thyroidal iodine uptake was assumed to be independent from age and taken to be about 1.7 the normal for an insufficient dictary iodine intake as in the Federal Republic of Germany.     

The effect of Mn2+ on thyroid iodine metabolism in rats]

Injection into rats of manganous chloride (2 mg/100 g) showed, after a 24-hr period, a marked depression of thyroidal 131I uptake. There is a decrease in serum T3 and T4 levels and an increase in I- level. These results demonstrate that the action of manganous ions is to block uptake of I- by the thyroid.     

Factors Associated With Radioactive Iodine Therapy–Acquired Nasolacrimal Duct Obstruction

ObjectiveTo identify factors associated with radioactive iodine (RAI)-acquired nasolacrimal duct obstruction (NLDO).MethodsRetrospective chart review and telephone surveys of patients who received RAI therapy for thyroid carcinoma at an academic institution were conducted. Telephone surveys were used to screen for post-RAI NLDO diagnoses. Databases were reviewed for documented NLDO, demographics, RAI dose, total number of RAI treatments, and sialadenitis. Routine post-RAI whole-body scintigraphy (WBS) images were analyzed for the presence or absence of ¹³¹I sodium iodide (I-131) in the nasolacrimal duct. Intranasal I-131 activity was graded as none, low, moderate, and high; those with moderate or high activity were considered to have “increased” activity. Logistic and ordinal logistic regression models were used to evaluate the associations with NLDO while adjusting for I-131 dose.ResultsOf the 209 patients who completed the survey, 15 (7%) had NLDO diagnoses. Increased intranasal I-131 activity on WBS, presence of nasolacrimal I-131 WBS activity, presence of documented post-RAI sialadenitis, and history of >1 RAI treatment were associated with the development of NLDO from univariate analyses (P ≤ .013). After adjusting for the administered dose of I-131, the presence of sialadenitis and nasolacrimal I-131 activity on WBS were the remaining 2 factors significantly associated with NLDO development (P < .001 and P = .01, respectively).ConclusionsThe presence of sialadenitis and nasolacrimal I-131 activity on WBS are I-131 dose-independent correlative factors for RAI-associated NLDO. Patients with these characteristics should be counseled on their increased risk of NLDO after RAI therapy for thyroid carcinoma.     

Analysis of thyroid cancer data from the Ukraine after ’Chernobyl’ using a two-mutation carcinogenesis model

The thyroid cancer data of children in the northern regions of the Ukraine after the reactor accident at Chernobyl were combined with thyroid dose measurements in the same regions and analysed using a two- mutation carcinogenesis model. The best fit was obtained for radiation acting as an initiating agent, i.e. on the first mutation of the model. The observed relatively high increase of thyroid cancer incidence after 1990 in children exposed to radiation released after the reactor accident could be ascribed to the high thyroid doses and the relatively low background thyroid cancer incidence in children. The maximum annual incidence is predicted to occur fairly soon after the reactor accident, i.e. about 10 years. For adults, the predicted relative increase of annual thyroid cancers is much lower than for children younger than 20 years. The modelling results are used to derive risk estimates for radiation-induced thyroid cancer. These risk estimates are dependent on age at exposure, follow-up time and the background thyroid cancer incidence. The calculated excess absolute risk for a population of all ages is about one-third of that currently used by ICRP, but for children the calculated absolute risks are about a factor of 3 higher than derived in other epidemiological studies. The model results indicate that the excess absolute radiation risk per unit dose for children is about the same as or a little lower than that for adults. Received: 11 May 1999 / Accepted: 30 December 1999     

XB130, a New Adaptor Protein,Regulates Expression of Tumor Suppressive MicroRNAs in Cancer Cells

XB130, a novel adaptor protein, promotes cell growth by controlling expression of many related genes. MicroRNAs (miRNAs), which are frequently mis-expressed in cancer cells, regulate expression of targeted genes. In this present study, we aimed to explore the oncogenic mechanism of XB130 through miRNAs regulation. We analyzed miRNA expression in XB130 short hairpin RNA (shRNA) stably transfected WRO thyroid cancer cells by a miRNA array assay, and 16 miRNAs were up-regulated and 22 miRNAs were down-regulated significantly in these cells, in comparison with non-transfected or negative control shRNA transfected cells. We chose three of the up-regulated miRNAs (miR-33a, miR-149 and miR-193a-3p) and validated them by real-time qRT-PCR. Ectopic overexpression of XB130 suppressed these 3 miRNAs in MRO cells, a cell line with very low expression of XB130. Furthermore, we transfected miR mimics of these 3 miRNAs into WRO cells. They negatively regulated expression of oncogenes (miR-33a: MYC, miR-149: FOSL1, miR-193a-3p: SLC7A5), by targeting their 3′ untranslated region, and reduced cell growth. Our results suggest that XB130 could promote growth of cancer cells by regulating expression of tumor suppressive miRNAs and their targeted genes.     

Irradiation and second cancers. The thyroid as a case in point

The thyroid gland is highly sensitive to radiation during childhood: the risk of thyroid tumours is increased for mean doses as low as 100 mGy and for higher doses, the risk increases linearly with the dose. Excess relative risk is important, being 7.7 for 1 Gy delivered to the thyroid gland during childhood. The risk of thyroid tumours is modified by several factors: a) age at exposure: in childhood, the risk decreases with increasing age at exposure and is not significant after 20 years; b) gender: females are two times more likely than males to develop thyroid tumours; c) genetic predisposition due to a defect in DNA repair mechanisms, and dietary and hormonal factors may modify the risk; d) the influence of fractionation and dose rate is not well established. Radioiodine 131 (1311) used for medical purposes has almost no tumourigenic effect on the adult thyroid gland. The consequences of the Chernobyl accident have clearly shown that the risk of thyroid cancer after exposure to 1311 in childhood is important, and that such exposure should be prevented by potassium iodine prophylaxis. RET/PTC rearrangements are found in 60-80% of papillary carcinomas and in 45% of adenomas occurring after radiation exposure. They are found in 5-15% of papillary carcinoma and in no follicular adenomas that occurred in the absence of radiation exposure.     

Lithuanian cohort of Chernobyl cleanup workers: Cancer incidence follow-up 1986–2012

BackgroundCancer risks following radiation exposure in adulthood after Chernobyl are less studied compared to those after exposure in childhood. We aimed to evaluate cancer risk in the Lithuanian cohort of Chernobyl cleanup workers 26 years after their exposure in Chernobyl.MethodsStudy population (6707 men) was followed for cancer incidence upon return from Chernobyl till the end of 2012 by linkage procedure with the Lithuanian Cancer Registry and for migration and death – with Central Population Registry. The site-specific cancer risk in the cohort was estimated by calculating the standardised incidence ratio (SIR) with 95 % confidence interval (CI).ResultsA total of 596 cancer cases was observed in the cohort, against 584 expected (SIR 1.02; 95 % CI 0.94, 1.11). Only incidence of mouth and pharynx cancers was increased compared to the expected (SIR 1.41; 95 % CI 1.07, 1.86). Nevertheless, an increased risk of thyroid cancer was observed among cleanup workers who were younger than 30 years when entering the Chernobyl zone (SIR 2.90; 95 % CI 1.09, 7.72), whose radiation dose was above 100 milisievert (mSv) (SIR 3.13; 95 % CI 1.30, 7.52) and who had shorter duration of stay (SIR 2.30; 95 % CI 1.03, 5.13).ConclusionsOur findings are consistent with those observed in other cohorts of workers, namely, the increased risk of cancer sites related to behavioural factors. The increased risk of thyroid cancer among cleanup workers who were younger than 30 years when entering Chernobyl and whose radiation dose was above 100 mSv cannot exclude the association with the radiation exposure in Chernobyl.     

Post-Chernobyl thyroid cancers in Ukraine. Report 2: risk analysis

On April 26, 1986, the worst nuclear reactor accident to date occurred at the Chornobyl (Chernobyl) power plant in Ukraine. Millions of people in Ukraine, Belarus and Russia were exposed to radioactive nuclides, especially (131)I. Since then, research has been conducted on various subgroups of the exposed population, and it has been demonstrated that the large increase in thyroid cancer is related to the (131)I exposure. However, because of study limitations, quantified risk estimates are limited, and there remains a need for additional information. We conducted an ecological study to investigate the relationship between (131)I thyroid dose and the diagnosis of thyroid cancer in three highly contaminated oblasts in Northern Ukraine. The study population is comprised of 301,907 persons who were between the ages of 1 and 18 at the time of the Chornobyl accident and were living in 1,293 rural settlements in the three study oblasts. Twenty-four percent of the study population had individual thyroid dose estimates and the other 76% had "individualized" estimates of thyroid dose based on direct thyroid measurements taken from a person of the same age and gender living in the same or nearby settlement. Cases include 232 thyroid cancers diagnosed from January 1990 through December 2001, and all were confirmed histologically. Dose-response analyses took into account differences in the rate of ultrasound examinations conducted in the three study oblasts. The estimated excess relative risk per gray was 8.0 (95% CI = 4.6-15) and the excess absolute risk per 10,000 person-year gray was estimated to be 1.5 (95% CI = 1.2-1.9). In broad terms, these estimates are compatible with results of other studies from the contaminated areas, as well as studies of external radiation exposure.     

Radioimmunotherapy for breast cancer: treatment of a patient with I-131 L6 chimeric monoclonal antibody.

We report the first treatment of metastatic breast cancer by systemic radioimmunotherapy. The serial therapy doses were chosen based on quantitative imaging data in a treatment planning approach. A terminally ill patient with aggressive, locally advanced breast cancer who had failed radiation treatment and chemotherapy was injected intravenously with radiolabeled I-131 chimeric L6, a human-mouse chimeric lgG1 monoclonal antibody to adenocarcinoma. Initially, an imaging 10 mCi dose of I-131 chimeric L6 (dose 1) deposited 8.8% of the injected dose in her chest wall tumor at 48 hours. Ten days later the patient was given a 150 mCi I-131 chimeric L6 dose (dose 2) followed three weeks later by a 100 mCi dose (dose 3). Tumor uptake and retention were comparable for doses 1 and 2, and decreased for dose 3. Following dose 3 the patient developed a manageable thrombocytopenia and transient Grade IV granulocytopenia. The tumor was observed to decrease in size with peak tumor regression occurring two weeks after dose 3. This partial response (PR) was achieved by radioimmunotherapy at a time when conventional therapy had been unable to impact the growth of the patient's massive and aggressive tumor.     

Protective effects of <Emphasis Type="SmallCaps">l</Emphasis>-selenomethionine on space radiation induced changes in gene expression

Ionizing radiation can produce adverse biological effects in astronauts during space travel. Of particular concern are the types of radiation from highly energetic, heavy, charged particles known as HZE particles. The aims of our studies are to characterize HZE particle radiation induced biological effects and evaluate the effects of l-selenomethionine (SeM) on these adverse biological effects. In this study, microarray technology was used to measure HZE radiation induced changes in gene expression, as well as to evaluate modulation of these changes by SeM. Human thyroid epithelial cells (HTori-3) were irradiated (1 GeV/n iron ions) in the presence or in the absence of 5 μM SeM. At 6 h post-irradiation, all cells were harvested for RNA isolation. Gene Chip U133Av2 from Affymetrix was used for the analysis of gene expression, and ANOVA and EASE were used for a determination of the genes and biological processes whose differential expression is statistically significant. Results of this microarray study indicate that exposure to small doses of radiation from HZE particles, 10 and 20 cGy from iron ions, induces statistically significant differential expression of 196 and 610 genes, respectively. In the presence of SeM, differential expression of 77 out of 196 genes (exposure to 10 cGy) and 336 out of 610 genes (exposure to 20 cGy) is abolished. In the presence or in the absence of SeM, radiation from HZE particles induces differential expression of genes whose products have roles in the induction of G1/S arrest during the mitotic cell cycle, as well as heat shock proteins. Some of the genes, whose expressions were affected by radiation from HZE particles and were unchanged in irradiated cells treated with SeM, have been shown to have altered expression levels in cancer cells. The conclusions of this report are that radiation from HZE particles can induce differential expression of many genes, some of which are known to play roles in the same processes that have been shown to be activated in cells exposed to radiation from photons (like cell cycle arrest in G1/S), and that supplementation with SeM abolishes HZE particle-induced differential expression of many genes. Understanding the roles that these genes play in the radiation-induced transformation of cells may help to decipher the origins of radiation-induced cancer.     

Screening effects in risk studies of thyroid cancer after the Chernobyl accident

In this article scenarios have been developed, which simulate screening effects in ecological and cohort studies of thyroid cancer incidence among Ukrainians, whose thyroids have been exposed to ¹³¹I in the aftermath of the Chernobyl accident. If possible, the scenarios were based on directly observed data, such as the population size, dose distributions and thyroid cancer cases. Two scenarios were considered where the screening effect on baseline cases is either equal to or larger than that of radiation-related thyroid cancer cases. For ecological studies in settlements with more than ten measurements of the ¹³¹I activity in the human thyroid in May–June 1986, the screening bias appeared small (<19%) for all risk quantities. In the cohort studies, the excess absolute risk per dose was larger by a factor of 4 than in the general population. For an equal screening effect on baseline and radiation-related cancer (Scenario 1) the excess relative risk was about the same as in the general population. However, a differential screening effect (Scenario 2) produced a risk smaller by a factor of 2.5. A comparison with first results of the Ukrainian–US-American cohort study did not give any indication that a differential screening effect has a marked influence on the risk estimates. The differences in the risk estimates from ecological studies and cohort studies were explained by the different screening patterns in the general population and in the much smaller cohort. The present investigations are characterized by dose estimates for many settlements which are very weakly correlated with screening, the confounding variable. The results show that under these conditions ecological studies may provide risk estimates with an acceptable bias.     

Risk of thyroid cancer among Chernobyl emergency workers of Russia

The presented paper deals with the thyroid cancer incidence in selected cohorts of emergency workers of Russia. In 1986-2003, a total of 87 cases of thyroid cancer were observed. Based on these data, a statistically significant increase in thyroid cancer incidence was found above the reference level for the male population of Russia, corresponding to a standardized incidence rate (SIR) of SIR = 3.47 [95% confidence interval (CI): 2.80; 4.25]. The highest incidence rate (SIR = 6.62, 95% CI: 4.63; 9.09) was shown for those emergency workers who took part in the early recovery operations in April-July 1986. The estimated SIR value increases to 7.97 (95% CI: 5.24; 11.52) after allowing for a 10 years latent period of Chernobyl-related thyroid cancers. These results indicate that the exposure to incorporated (131)I was the major risk factor of thyroid cancer among Chernobyl emergency workers. No statistically significant relationship was found for the thyroid cancer incidence and external radiation dose.