USE OF ANTHROPOMORPHIC HETEROGENEOUS PHYSICAL PHANTOMS FOR VALIDATION OF COMPUTATIONAL DOSIMETRY OF MEDICAL PERSONNEL AND PATIENTS. / VYKORYSTANNIa ANTROPOMORFNYKh GETEROGENNYKh FIZYChNYKh FANTOMIV DLIa VALIDATsIÏ ROZRAKhUNKOVOÏ DOZYMETRIÏ PERSONALU TA PATsIIeNTIV.

In the dosimetry of ionizing radiation, the phantoms of the human body, which are used as a replacement for thehuman body in physical measurements and calculations, play an important, but sometimes underestimated, role.There are physical phantoms used directly for measurements, and mathematical phantoms for computationaldosimetry. Their complexity varies from simple geometry applied for calibration purposes up to very complex, whichsimulates in detail the shapes of organs and tissues of the human body. The use of physical anthropomorphic phantoms makes it possible to effectively optimize radiation doses by adjusting the parameters of CT-scanning (computed tomography) in accordance with the characteristics of the patient without compromising image quality. The useof phantoms is an indispensable approach to estimate the actual doses to the organs or to determine the effectivedose of workers - values that are regulated, but cannot be directly measured.The article contains an overview of types, designs and the fields of application of anthropomorphic heterogeneousphysical phantoms of a human with special emphasis on their use for validation of models and methods of computational dosimetry.

THE REQUIREMENTS FOR PERSONAL MONITORING OF OCCUPATIONAL EXPOSURE: INTERNATIONAL EXPERIENCE AND UKRAINIAN REALITIES. / VYMOGY DO INDYVIDUAL'NOGO DOZYMETRYChNOGO KONTROLIu PROFESIINOGO OPROMINENNIa: SVITOVYI DOSVID TA UKRAÏNS'KI REALIÏ.

The article includes analysis and generalizations about international and national experience as well as regulatory requirements for the organization and performance of occupational monitoring for radiation exposure (category A personnel), filling of the national dose registries. It is shown that for practical reasons it is justifiable to provide universal individual monitoring of category A personnel, regardless of the expected dose of radiation. The establish ment and functioning the national dose registry should not be limited to the mechanical collection and accumulation of data of non-guaranteed quality. Instead, both a quality management program and a scientific and methodological center should become components of the dose monitoring and registration system ensuring the quality and reliability of data on occupational exposure doses. Besides the dose records, the data sets should include information about methods used, work conditions, employees' health status. Information exchange infrastructure and data protection policies should be built in accordance with national approaches under the auspices of the State Agency for E-Governance in Ukraine.

RADIATION RISKS OF THYROID CANCER IN CHORNOBYL CLEAN-UP WORKERS USING THE ALTERNATIVE ESTIMATES OF DOSES OF EXTERNAL EXPOSURE. / RADIATsIINI RYZYKY RAKU ShchYTOPODIBNOÏ ZALOZY V UChASNYKIV LIKVIDATsIÏ AVARIÏ NA ChAES Z URAKhUVANNIaM AL'TERNATYVNYKh OTsINOK DOZ ZOVNIShN'OGO OPROMINENNIa.

OBJECTIVE: The objective of this study was to estimate the thyroid cancer radiation risks - excess absolute risk(EAR), excess relative risk (ERR) and attributable fraction of risk (AR) in the cohort of 150,813 Ukrainian male clean-up workers during the 1986-2012 period (more than 25 years after the Chornobyl accident). MATERIALS AND METHODS: The cohort under study of 150,813 Ukrainian men who participated emergency and clean-up work in 1986-1990 was formed based on the data of the Ukrainian State Register of persons affected due toChornobyl accident (SRU). The identification of thyroid cancer cases (216) was carried out by linking the SRU data-base with the National Cancer Registry of Ukraine (NCRU) data. Standardised incidence ratios (SIR) were estimatedcomparing thyroid cancer incidence in the cohort with the corresponding national indices. Excess absolute risk(EAR), excess relative risk (ERR) and attributable fraction of risk (AR) were calculated accounting for the alterna-tive dose estimates. The following sources of the average dose values for Ukrainian liquidators were used: officialtotal external dose records according to UNSCEAR 2008 report and results of external red bone marrow dose recon-struction by the RADRUE method for the cohort sample. For the radiation risk evaluation, these estimates were con-versed to the average external thyroid dose. RESULTS: Results of the long term study (1986-2012) of thyroid cancer risks in a cohort of 150813 Chornobyl clean-up workers («liquidators¼) from Ukraine are presented. Two options for the average thyroid dose estimates were usedfor radiation risks evaluation. According to the SRU and NCRU 216 incident thyroid cancers were diagnosed in 1986-2012 within the studied cohort with an overall SIR of 3.35 (95 % confidence interval (CI) 2.51-3.80). The SIR esti-mates were elevated throughout the entire follow-up period. Investigation of a contribution of the external expo-sure (according to the alternative values) showed the elevated dose associated thyroid cancer rates in the studiedcohort. Alternatively estimated EAR/104 PY Gy were of 1.86 (95 % CI 0.47-3.24) and 2.07 (95 % CI 0.53-3.62);ERR/Gy - 2.38 (95 % CI 0.60-4.15) and 2.66 (95 % CI 0.68-4.64) and AR % (Gy) 70.4 % and 72.7 % Gy. CONCLUSIONS: Obtained results prove the dose dependent increase of thyroid cancer incidence among UkrainianChornobyl clean-up workers. These conclusions are consistent with those received for combined cohort of Belarus,Russia and Baltic States liquidators.

Buccal mucosa micronuclei counts in relation to exposure to low dose-rate radiation from the Chornobyl nuclear accident and other medical and occupational radiation exposures.

BACKGROUND: Ionizing radiation is a well-known carcinogen. Chromosome aberrations, and in particular micronuclei represent an early biological predictor of cancer risk. There are well-documented associations of micronuclei with ionizing radiation dose in some radiation-exposed groups, although not all. That associations are not seen in all radiation-exposed groups may be because cells with micronuclei will not generally pass through mitosis, so that radiation-induced micronuclei decay, generally within a few years after exposure. METHODS: Buccal samples from a group of 111 male workers in Ukraine exposed to ionizing radiation during the cleanup activities at the Chornobyl nuclear power plant were studied. Samples were taken between 12 and 18 years after their last radiation exposure from the Chornobyl cleanup. The frequency of binucleated micronuclei was analyzed in relation to estimated bone marrow dose from the cleanup activities along with a number of environmental/occupational risk factors using Poisson regression adjusted for overdispersion. RESULTS: Among the 105 persons without a previous cancer diagnosis, the mean Chornobyl-related dose was 59.5 mSv (range 0-748.4 mSv). There was a borderline significant increase in micronuclei frequency among those reporting work as an industrial radiographer compared with all others, with a relative risk of 6.19 (95% CI 0.90, 31.08, 2-sided p = 0.0729), although this was based on a single person. There was a borderline significant positive radiation dose response for micronuclei frequency with increase in micronuclei per 1000 scored cells per Gy of 3.03 (95% CI -0.78, 7.65, 2-sided p = 0.1170), and a borderline significant reduction of excess relative MN prevalence with increasing time since last exposure (p = 0.0949). There was a significant (p = 0.0388) reduction in MN prevalence associated with bone X-ray exposure, but no significant trend (p = 0.3845) of MN prevalence with numbers of bone X-ray procedures. CONCLUSIONS: There are indications of increasing trends of micronuclei prevalence with Chornobyl-cleanup-associated dose, and indications of reduction in radiation-associated excess prevalence of micronuclei with time after exposure. There are also indications of substantially increased micronuclei associated with work as an industrial radiographer. This analysis adds to the understanding of the long-term effects of low-dose radiation exposures on relevant cellular structures and methods appropriate for long-term radiation biodosimetry.

The characteristics of antibodies of mice immunized by human unconventional myosin 1c.

Specific antibodies produced against a protein of interest are invaluable tools for monitoring the protein structure, intracellular location and biological activity. Inoculation of murine lymphoma cells into the peritoneal cavity of immunized mice provides generation of ascitic fluid containing a significant amount of antibody with desired antigen specificity. Here we demonstrated that the intraperitoneal administration of murine lymphoma NK/Ly cells in mice immunized with 48 kDa isoform of human blood serum unconventional myosin 1c leads to generation of ascitic fluid that contained specific IgG-antibodies. These antibodies were capable of binding of the unconventional myosin 1c isolated from blood serum of patients with multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosis, and could be used for diagnostics of several autoimmune diseases, the multiple sclerosis in particular.

Study of antineoplastic action of novel isomeric derivatives of 4-thiazolidinone.

Pyrazole- and aryl-substituted derivatives of 4-thiazolidinone belong to a perspective group of compounds with potential antitumor action. Earlier, we have demonstrated high toxicity in vitro of several 4-thiazolidinones derivatives towards tumor cell lines. To further enhance the antitumor activity of novel 4-thiazolidinones, their chemical scaffold was optimized, and new pyrazole-thiazolidinones were synthesized. That allowed us to combine in one molecule the potential pharmacophore centres of previously tested compounds. As a result, "hybrid" 4-thiazolidinones exhibit higher toxicity in vitro toward tumor cells of various origin. The molecular mechanisms of antineoplastic activity of these compounds and intensity of induction of apoptosis strongly depended on the position of the substituent in the thiazolidinone cycle. In particular, Les-3661 compound, containing pyrazoline fragment in the 4th position of thiazolidinone core, exhibits 14 times higher cytotoxic activity towards tumor cells (LC50 = 3 µM) in comparison to its 2-substituted isomer Les-3713 (LC50 = 42 µM). It is demonstrated that in terms of underlying molecular mechanisms for cytotoxic effect the Les-3661 compound induced caspase-8 and caspase-9 dependent mixed-type of apoptosis, while Les-3713 induced apoptosis mediated only by the caspase-8.

Testing and validation of methods for dose measuring in anisotropic fields under occupational exposure in interventional cardiology.

STUDY OBJECTIVE: Experimental testing of the practical application of methodology developed for the individual effective doses assay in an NPP staff by means of 4 dosimeters in case of non-uniform external γ-exposure with known angular characteristics of the radiation field. MATERIALS AND METHODS: Two series of experimental phantom measurements were held at the workplaces of interventional cardiologists during a procedures in an X-ray operating room. RESULTS AND CONCLUSIONS: Dose fields in a body of healthcare professional are characterized by the high gradients and readings of individual dosimeters depending on location can differ from 1.5 to 10 times. Thus a single dosimeter is not a source of sufficient information for accurate estimation of an effective dose. Studies have confirmed the possibility of NPP technique application at the workplace of interventional cardiologist. The essential need for a strict control of the eye lens doses is demonstrated.

Methodological approach to developing of double dosimetry algorithms and its application in the interventional cardiology.

STUDY OBJECTIVES: to develop taking into account the specifity of exposure conditions a new algorithm for interventional cardiologists who use the X-ray protective clothes. MATERIALS AND METHODS: modelling of the typical conditions of radiation exposure of interventional cardiologist wearing protective clothes during the interventions, providing Monte-Carlo computations of organ doses and dosimeters readouts. RESULTS: partial dose values for all possible radiation conditions and relative frequency weight coefficients for each condition were obtained by Monte-Carlo method. CONCLUSIONS: flexible and adaptive methodology for algorithm developing was proposed, a more specific algorithm was obtained for typical radiation conditions occuring under the interventional cardiology procedures. This algorithm well corresponded to experimental measurements demonstrating at that less conservatism comparing to other known algorithms.

Multiple myeloma among Chornobyl accident clean-up workers - state and perspectives of analytical study.

UNLABELLED: The objective of the study was to analyze the Multiple Myeloma (MM) incidence in clean-up workers preparing the information background for consequent analytical study with a dose-dependent risk estimates. MATERIALS AND METHODS: The Cohort Database was linked to the Ukrainian National Cancer Registry to identify the MM cases in a cohort of 152 520 male clean-up workers. RESULTS: The 64 MM cases were identified in the studied Cohort for the 1987-2012 period. Fifty-eight of them were included to the preliminary incidence analysis accounting for the 10-years lag-period. According to the preliminary data analysis the MM incidence rate in studied clean-up workers Cohort did not exceed the corresponding rate in general population of Ukraine along the 21 years after the catastrophe. CONCLUSIONS: Standardized incidence ratio for the 2008-2012 period, that is 22-26 years after the accident, demonstrated the significant excess of MM incidence among male clean-up workers in comparison with general population of Ukraine of corresponding age and gender (SIR 1.61, 95% CI 1.01;2.21).

Dosimetry for a study of low-dose radiation cataracts among Chernobyl clean-up workers.

A cohort of 8,607 Ukrainian Chernobyl clean-up workers during 1986-1987 was formed to study cataract formation after ionizing radiation exposure. Study eligibility required the availability of sufficient exposure information to permit the reconstruction of doses to the lens of the eye. Eligible groups included civilian workers, such as those who built the "sarcophagus" over the reactor, Chernobyl Nuclear Power Plant Workers, and military reservists who were conscripted for clean-up work. Many of the official doses for workers were estimates, because only a minority wore radiation badges. For 106 military workers, electron paramagnetic resonance (EPR) measurements of extracted teeth were compared with the recorded doses as the basis to adjust the recorded gamma-ray doses and provide estimates of uncertainties. Beta-particle doses to the lens were estimated with an algorithm devised to take into account the nature and location of Chernobyl work, time since the accident, and protective measures taken. A Monte Carlo routine generated 500 random estimates for each individual from the uncertainty distributions of the gamma-ray dose and of the ratio of beta-particle to gamma-ray doses. The geometric mean of the 500 combined beta-particle and gamma-ray dose estimates for each individual was used in the data analyses. The median estimated lens dose for the cohort was 123 mGy, while 4.4% received >500 mGy.

Cataracts among Chernobyl clean-up workers: implications regarding permissible eye exposures.

The eyes of a prospective cohort of 8,607 Chernobyl clean-up workers (liquidators) were assessed for cataract at 12 and 14 years after exposure. The prevalence of strictly age-related cataracts was low, as expected (only 3.9% had nuclear cataracts at either examination), since 90% of the cohort was younger than 55 years of age at first examination. However, posterior subcapsular or cortical cataracts characteristic of radiation exposure were present in 25% of the subjects. The data for Stage 1 cataracts, and specifically for posterior subcapsular cataracts, revealed a significant dose response. When various cataract end points were analyzed for dose thresholds, the confidence intervals all excluded values greater than 700 mGy. Linear-quadratic dose-response models yielded mostly linear associations, with weak evidence of upward curvature. The findings do not support the ICRP 60 risk guideline assumption of a 5-Gy threshold for "detectable opacities" from protracted exposures but rather point to a dose-effect threshold of under 1 Gy. Thus, given that cataract is the dose-limiting ocular pathology in current eye risk guidelines, revision of the allowable exposure of the human visual system to ionizing radiation should be considered.

[The experience of FISH technique application for reconstruction of individual radiation doses in Chernobyl liquidators in the framework of Ukrainian-American project "Leukemia"].

The results of proper investigations received under the cytogenetic examination of 225 persons (control groups, Chernobyl liquidators exposed to different radiation doses, oncogematology patients) had been summarized and analyzed. The conclusion concerning possibilities and limitations of FISH technique usage for retrospective biodosimetry of human radiation exposure has been presented.

High precision EPR dosimetry as a reference tool for validation of other techniques.

We present here a particular application area for EPR dosimetry with teeth--use as a source of reference dose values for validation/verification of other retrospective dosimetry techniques and existing dose records. The conditions of application of EPR dosimetry in this role as well as practical design of such studies are shown. Particular attention is given to the requirements to the techniques in terms of precision and throughput, as well as to the issue of availability of samples for analysis and practical solution of this problem. Practical application of this approach is illustrated by several examples of completed validation sub-studies, which were performed in the framework of large-scale post-Chernobyl epidemiological studies.

Variability of parameters in retrospective EPR dosimetry with teeth for Ukrainian population.

Variability of EPR signal parameters in retrospective dosimetry with teeth has been studied among five different oblasts (regions) of Ukraine. It was found that the native signal in enamel is region-invariant and has peak-to-peak width of 0.85+/-0.01 mT and intensity of 1.0+/-0.20 normalized units. Low-frequency background signals in the spectra of enamel, expressed in terms of dose were estimated to represent 1520 mGy. Variability of radiation sensitivity among different teeth (inter-sample variability measured using 100 mg aliquots) was (+/-)4% while among different parts of one tooth (intra-sample variability measured using 5-10 mg aliquots)--(+/-)7%.

Relationship between protection and operational quantities in dosimetry of photon external exposure-deficiencies of Hp(10).

It is commonly assumed that, for a variety of conditions, the E/Hp(10) conversion coefficient is below unity, i.e., Hp(10) can be used as a conservative surrogate of effective dose. The validity of this assumption was checked by Monte Carlo simulation of E and Hp(10) as determined by a practical dosemeter. The calculations concerned irradiation by parallel photon beams with directions varying within a 4pi solid angle and energy ranging from 50 keV to 1 MeV. Observed dependences of conversion coefficients on irradiation geometry, photon energy and dosemeter position demonstrate that in strongly anisotropic radiation fields straightforward application of Hp(10) for assessment of effective dose may lead to significant underestimation of the latter. For photon energy of 80 keV this underestimation may be up to 16-fold. For simulation of real life situations, irradiation by photons coming within broad cones (with solid angle pi) was considered. It was found that even for this irradiation geometry, E/Hp(10) may be as high as 4.3. At the same time, for radiation coming from the frontal hemisphere, the values of the conversion coefficient for a typically positioned (i.e., the left chest pocket) personal dosemeter do not exceed unity. The conclusion was reached that prior to application of Hp(10) as a surrogate of effective dose, the information regarding angular distribution of radiation fields must be taken into account.

Some aspects of EPR dosimetry of liquidators.

Doses of few hundred liquidators were reconstructed using EPR dosimetric technique, developed and routinely used in SCRM. Both cumulative and accidental dose values were determined. Obtained results are analyzed and discussed.

Emerging technological bases for retrospective dosimetry.

In this article we discuss examples of challenging problems in retrospective dosimetry and describe some promising solutions. The ability to make measurements by accelerator mass spectrometry and luminescence techniques promises to provide improved dosimetry for regions of Belarus, Ukraine and Russian Federation contaminated by radionuclides from the Chernobyl accident. In addition, it may soon be possible to resolve the large neutron discrepancy in the dosimetry system for Hiroshima through novel measurement techniques that can be used to reconstruct the fast-neutron fluence emitted by the bomb some 51 years ago. Important advances in molecular cytogenetics and electron paramagnetic resonance measurements have produced biodosimeters that show potential in retrospective dosimetry. The most promising of these are the frequency of reciprocal translocations measured in chromosomes of blood lymphocytes using fluorescence in situ hybridization and the electron paramagnetic resonance signal in tooth enamel.

Estimation of 131I thyroid doses for the evacuees from Pripjat.

The thyroid doses of 49,360 inhabitants of Pripjat evacuated after the accident at Chernobyl were reconstructed. During their evacuation most of the evacuees passed through highly contaminated territories. The evaluation of a large-scale public survey showed that only about 50% of the evacuees had left the contaminated areas within 5 days and that 30% of them stayed there for more than 30 days. As a first step, the model of dose estimations was improved, and thyroid doses were assessed for the group of evacuees for whom the 131I activity in the thyroids was measured. The 131I incorporation during the first 5 days after the accident was described by a single-intake model (inhalation); later incorporations were assumed to be proportional to the radioiodine activity in milk. As a second step, the correlation between the calculated doses and individual parameters (place of residence in Pripjat, intake of stable iodine, and age at the time of the accident) was described by an empirical equation. This equation was applied to all evacuees who completed the questionnaires of the public survey. Previous dose assessments were found to overestimate the thyroid doses especially for the younger evacuees. On the basis of these estimations, collective doses and the resulting radiation risks for thyroid cancer were assessed for different age groups.

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.