Internal doses in experimental mice and rats following exposure to neutron-activated 56MnO2 powder: results of an international, multicenter study.

The experiment was performed in support of a Japanese initiative to investigate the biological effects of irradiation from residual neutron-activated radioactivity that resulted from the A-bombing. Radionuclide 56Mn (T1/2 = 2.58 h) is one of the main neutron-activated emitters during the first hours after neutron activation of soil dust particles. In our previous studies (2016-2017) related to irradiation of male Wistar rats after dispersion of 56MnO2 powder, the internal doses in rats were found to be very inhomogeneous: distribution of doses among different organs ranged from 1.3 Gy in small intestine to less than 0.0015 Gy in some of the other organs. Internal doses in the lungs ranged from 0.03 to 0.1 Gy. The essential pathological changes were found in lung tissue of rats despite a low level of irradiation. In the present study, the dosimetry investigations were extended: internal doses in experimental mice and rats were estimated for various activity levels of dispersed neutron-activated 56MnO2 powder. The following findings were noted: (a) internal radiation doses in mice were several times higher in comparison with rats under similar conditions of exposure to 56MnO2 powder. (b) When 2.74 × 108 Bq of 56MnO2 powder was dispersed over mice, doses of internal irradiation ranged from 0.81 to 4.5 Gy in the gastrointestinal tract (small intestine, stomach, large intestine), from 0.096 to 0.14 Gy in lungs, and doses in skin and eyes ranged from 0.29 to 0.42 Gy and from 0.12 to 0.16 Gy, respectively. Internal radiation doses in other organs of mice were much lower. (c) Internal radiation doses were significantly lower in organs of rats with the same activity of exposure to 56MnO2 powder (2.74 × 108 Bq): 0.09, 0.17, 0.29, and 0.025 Gy in stomach, small intestine, large intestine, and lungs, respectively. (d) Doses of internal irradiation in organs of rats and mice were two to four times higher when they were exposed to 8.0 × 108 Bq of 56MnO2 (in comparison with exposure to 2.74 × 108 Bq of 56MnO2). (e) Internal radiation doses in organs of mice were 7-14 times lower with the lowest 56MnO2 amount (8.0 × 107 Bq) in comparison with the highest amount, 8.0 × 108 Bq, of dispersed 56MnO2 powder. The data obtained will be used for interpretation of biological effects in experimental mice and rats that result from dispersion of various levels of neutron-activated 56MnO2 powder, which is the subject of separate studies.

Sharp Rise in Cosmic Ray Irradiation of Organisms on Earth Caused by a Nearby SN Shockwave Passage.

The work considers the modelling of nearby supernova (SN) effects on Earth's biosphere via cosmic rays (CRs) accelerated by shockwaves. The rise of the radiation background on Earth resulted from the external irradiation by CR high-energy particles and internal radiation in organisms by the decay of cosmogenic 14C is evaluated. We have taken into account that the CR flux near Earth goes up steeply when the shockwave crosses the Solar System, while in previous works the CR transport was considered as purely diffusive. Our simulations demonstrate a high rise of the external ionization of the environments at Earth's surface by atmospheric cascade particles that penetrate the first 70-100 m of water depth. Also, the cosmogenic 14C decay is able to irradiate the entire biosphere and deep ocean organisms. We analyzed the probable increase in mutation rate and estimated the distance between Earth and an SN, where the lethal effects of irradiation are possible. Our simulations demonstrate that for SN energy of around 1051 erg the lethal distance could be ∼18 pc.

Microdistribution of internal radiation dose in biological tissues exposed to 56Mn dioxide microparticles.

Manganese-56 (56Mn) was one of the dominant neutron-activated radionuclides during the first hours following the atomic-bombing of Hiroshima and Nagasaki. The radiation spectrum of 56Mn and the radiation emission from excited levels of 56Fe following 56Mn beta-decay include gamma-quanta, beta-particles, Auger electrons and X-rays. The dispersion of neutron activated 56Mn in the air can lead to entering of radioactive microparticles into the lungs. The investigation of spatial microdistribution of an internal dose in biological tissue exposed to 56Mn is an important matter with regards to the possible elevated irradiation of the lung alveoli and alveolar ducts. The Monte Carlo code (MCNP-4C) was used for the calculation of absorbed doses in biological tissue around 56Mn dioxide microparticles. The estimated absorbed dose has a very essential gradient in the epithelium cells of lung alveoli and alveolar duct: from 61 mGy/decay on the surface of simple squamous cells of epithelium to 0.15 mGy/decay at distance of 0.3 µm, which is maximal cell thickness. It has been concluded that epithelial cells of these pulmonary microstructures are selectively irradiated by low-energy electrons: short-range component of beta-particles spectrum and Auger electrons. The data obtained are important for the interpretation of biological experiments implementing dispersed neutron-activated 56Mn dioxide powder.

Exploring the Application of Bifunctional Metal Chelators in Treating Triple-Negative Breast Cancer.

Purpose: In this study, we independently synthesised and labelled a novel bidentate bifunctional chelating agent, 177Lu-3,4-HOPO-Cetuximab, that achieved tight binding between targeting and radioactivity, and evaluated its targeted killing ability of cells in vitro and in vivo. Method: 3,4-HOPO was successfully synthesised through a series of chemical steps using malt phenol as the raw material, which was then coupled with Cetuximab labelled with 177Lu. 177Lu-3,4-HOPO-Cetuximab and 177Lu-DOTA-Cetuximab was tested for its cell viability and cell-binding rate after different times and at different doses by CCK-8 and cell-binding experiments. 177Lu-3,4-HOPO-Cetuximab (~500 µCi) and 177Lu-DOTA-Cetuximab (~500 µCi) were injected into the tail vein of a subcutaneous metastasis mouse model of triple-negative breast cancer with a single injection, and tumour volume growth and body weight changes were regularly monitored for 20 days. The radioactivity distribution in nude mice was analysed after sacrifice, and the treated and untreated tumour tissues were analysed by HE staining. Result: The cell viability of 177Lu-3,4-HOPO-Cetuximab declined exponentially after treatment for 48 h at 50 Bq/mL to 500 kBq/mL, respectively; the cell activity was slowed down from 8 to 96 h at a dose of 500 kBq; while the binding rate of 4T1 cells in 177Lu-3,4-HOPO-Cetuximab from 1 to 24 h, respectively, increased logarithmically, which was similar with 177Lu-DOTA-Cetuximab. After 20 days of treatment, the body weight of nude mice with 177Lu-3,4-HOPO-Cetuximab and 177Lu-DOTA-Cetuximab were hardly changed, while the body weight with physiological saline decreased significantly. The tumour inhibition rate of the 177Lu-3,4-HOPO-Cetuximab and 177Lu-DOTA-Cetuximab were (37.03 ± 11.16)% and (38.7 ± 5.1)%; HE staining showed that tumour cells were affected by the action of 177Lu causing necrosis. Conclusion: The experiments showed that 177Lu-3,4-HOPO-Cetuximab has a certain targeted therapeutic ability for triple-negative breast cancer, and it is expected to become a potential targeted nuclear medicine treatment for triple-negative breast cancer.

RESULTS OF WBC-MONITORING OF FIREFIGHTERS PARTICIPATING IN RESPONSE TO CHORNOBYL FOREST FIRES IN APRIL-MAY 2020. / REZUL'TATY LVL-MONITORYNGU POZhEZhNYKh, ShchO BULY ZADIIaNI U GASINNI LISOVOÏ POZhEZhI V ZONI VIDChUZhENNIa ChAES U KVITNI­TRAVNI 2020 ROKU.

OBJECTIVE: of this study was to determine the levels of radionuclides in the rescuers' bodies of the SES during firefighting in the exclusion zone of the Chornobyl nuclear power plant and to assess the dose of internal radiation dueto this receipt. MATERIALS AND METHODS: From 06.04.2020 to 19.05.2020 in the State Institution «National Research Center forRadiation Medicine of the National Academy of Medical Sciences of Ukraine¼ (NRCRM) measurements of the contentof incorporated gamma radionuclides on whole body counters (WBC) operational class «Screener-3M¼ (Minimumdetected activity (MDA) is 300-500 Bq for 5 minutes of measurement at 137Cs) and expert high-sensitivity WBC (MDAis 20 Bq for 10 minutes of measurement at 137Cs). 470 people (523 measurements) in three groups of personnel ofthe SES of Ukraine who took part in the forest fire liquidation in the exclusion zone in the period from April 4 toMay 5, 2020 were examined. Mathematical and spectrometric methods are used in the work. RESULTS AND CONCLUSIONS: In the vast majority (95 %) of the personnel of the SES of Ukraine, examined at the WBCoperational class «Screener-3M¼ (more than 500 measurements), the assessment of the values of the individualeffective dose of internal radiation due to 137Cs in the body during firefighting, assuming that it receipt occurredduring operation in the exclusion zone, did not exceed the minimum dose detected by MDD (5-14 µSv). The average value of the effective dose of internal radiation in the group of personnel of the State Emergency Service ofUkraine in Kyiv, which participated in the elimination of forest fires in the exclusion zone from April 4 to May 5, 2020(26 people) studied at the expert WBC, is 2.5 ± 1.1 µSv, in the group of personnel of the SES of Ukraine in Cherkasyregion, which participated in the fire on April 19-24, 2020 (9 people) - 2.2 ± 0.6 µSv, in the group of personnel ofthe SES of Ukraine in the Kyiv region, which took part in the elimination of the forest fire in the exclusion zone onApril 4 - May 5, 2020 (42 people) - 4.4 ± 2.4 µSv. Maximum values of 5.1 µSv, 3.5 µSv, 11.8 µSv in the groups ofKyiv city, Cherkasy and Kyiv regions, respectively, which is much lower than the basic dose limit for the populationfrom man-made sources of 1000 µSv · year-1 according to the Law of Ukraine about protection of the person againstinfluence of ionizing radiation.

Quantitative γ-H2AX immunofluorescence method for DNA double-strand break analysis in testis and liver after intravenous administration of 111InCl3.

BACKGROUND: It is well known that a severe cell injury after exposure to ionizing radiation is the induction of DNA double-strand breaks (DSBs). After exposure, an early response to DSBs is the phosphorylation of the histone H2AX molecule regions adjacent to the DSBs, referred to as γ-H2AX foci. The γ-H2AX assay after external exposure is a good tool for investigating the link between the absorbed dose and biological effect. However, less is known about DNA DSBs and γ-H2AX foci within the tissue microarchitecture after internal irradiation from radiopharmaceuticals. Therefore, in this study, we aimed to develop and validate a quantitative ex vivo model using γ-H2AX immunofluorescence staining and confocal laser scanning microscopy (CLSM) to investigate its applicability in nuclear medicine dosimetry research. Liver and testis were selected as the organs to study after intravenous administration of 111InCl3. RESULTS: In this study, we developed and validated a method that combines ex vivo γ-H2AX foci labeling of tissue sections with in vivo systemically irradiated mouse testis and liver tissues. The method includes CLSM imaging for intracellular cell-specific γ-H2AX foci detection and quantification and absorbed dose calculations. After exposure to ionizing radiation from 111InCl3, both hepatocytes and non-hepatocytes within the liver showed an absorbed dose-dependent elevation of γ-H2AX foci, whereas no such correlation was seen for the testis tissue. CONCLUSION: It is possible to detect and quantify the radiation-induced γ-H2AX foci within the tissues of organs at risk after internal irradiation. We conclude that our method developed is an appropriate tool to study dose-response relationships in animal organs and human tissue biopsies after internal exposure to radiation.

EPIDEMIOLOGICAL STUDIES OF CEREBROVASCULAR DISEASE OF THE POPULATION EVACUATED FROM THE 306KM ZONE OF THE ChNPP AT THE AGE OF 18-60 YEARS. ANALYSIS OF THE INFLUENCE OF INTERNAL IONIZING RADIATION ON THE THYROID GLAND 131I. / EPIDEMIOLOGIChNI DOSLIDZhENNIa TsEREBROVASKULIaRNOÏ ZAKhVORIuVANOSTI NASELENNIa, EVAKUIOVANOGO IZ 306KM ZONY ChAES U VITsI 18­60 ROKIV. ANALIZ VPLYVU VNUTRIShN'OGO IONIZUIuChOGO OPROMINENNIa ShchYTOPODIBNOÏ ZALOZY 131I.

Cohort epidemiological study of cerebrovascular diseases (CVD) was conducted in population evacuated from the30-km zone of the ChNPP been adult at the time of the accident (age 18-60). Study period was 1988-2016. Reviewof the specific CVD link with internal thyroid radiation dose from 131I has been made. OBJECTIVE: Establishing the time pattern of CVD morbidity in population evacuated from the ChNPP exclusion zonebeen adult at the time of the accident, depending on age, sex, time after the accident and internal thyroid radiation dose from 131I. MATERIALS AND METHODS: Data of the State Register of Ukraine on persons who survived after the ChNPP accident(SRU). The time pattern of morbidity was studied according to the observation periods (1988-1992; 1993-1997;1998-2002; 2003-2007; 2008-2012 and 2013-2016), taking into account age, sex and thyroid radiation dose. Theresearch cohort included 42,982 people with 18,133 men and 24,849 women among them. Data on the thyroid radiation doses in the SRU are seriously limited. Personal data on the radiation dose are available only in 957 people who just were included in the especially studied cohort. Dose intervals 0-0.3, 0.31-0.75, 0.76-2.0 Gy were adopted to review the influence of radiation factor on the CVD development. The data analysis was conducted on a mixed cohort of two age groups under the emergence of radiation effects (the «early¼ stage, covering the first 6 years from the moment of the accident, the «remote¼ stage - from 1998 to 2007, the «late¼ stage - 2008-2016). RESULTS: Study results indicate that the post-accident period is characterized by an increase in the level of CVD. The incidence rate increase occurred in the second observation period (1993-1997), that is, 6 years after the accident, regard-less of sex and age at the time of the accident. The peak of the incidence occurs in the third and fourth periods(1998-2002 and 2003-2007) of observation. Since 2008 there is a gradual decrease in morbidity. In all periods of observation the higher levels of CVD were registered in older people, i.e. 40-60 years at the time of an accident. In the first11 post-accidental years the higher levels of CVD incidence were observed in women, but in a later period after an acci-dent (12-26 years) in men. At a dose interval of 0.31-0.75 Gy a reliable link was established between the level of CVDwith the with internal thyroid radiation dose from 131I. In other dose intervals the dose-dependent effects are unstable. CONCLUSIONS: The post-accident period was marked by a significant increase in the level of CVD morbidity in theadult evacuees from the 30-km zone of the ChNPP. The incidence rate increase occurred since the 7th till the 21styearafter the ChNPP accident with the peak of morbidity from 12th to 21st years upon the accident. In the period that covered 22-30 years a decrease in the incidence rate was established. Connection of the specific forms of CVD with internal thyroid radiation dose from 131I has been established.

RESULTS OF COMPREHENSIVE RADIOLOGICAL - HYGIENIC MONITORING IN SOME SETTLEMENTS OF RADIOLOGICALLY CONTAMINATED AREAS IN RIVNE REGION IN 2017. / REZUL'TATY KOMPLEKSNOGO RADIATsIINO/GIGIIeNIChNOGO MONITORYNGU OKREMYKh NASELENYKh PUNKTIV RADIOAKTYVNO ZABRUDNENYKh TERYTORII RIVNENS'KOÏ OBLASTI U 2017 r.

OBJECTIVE: Identification of the main factors of radiation exposure formation in the residents of surveyed settle-ments of radiologically contaminated territories in Rivne region and estimation of radiation doses in population ata current stage of the accident. MATERIALS AND METHODS: Comprehensive radiological and hygienic monitoring was conducted within 7 settlementsof the Rokytnivsky district of Rivne region, namely in the Stare Selo, Vezhytsya, Perehodychi, Drozdyn', Berezove,Zabolottya, and Hrabun' villages. Assay of the incorporated 137Cs was held using a whole-body counter in residentsof the villages twice a year, i.e. in May and October. Basic foodstuffs were sampled for the assay of 90Sr and 137Cs alongwith interview of residents about the foodstuff consumption. External radiation doses were estimated. Mathe-matical, dosimetric, and radiochemical methods were applied. RESULTS AND CONCLUSIONS: The annual effective exposure doses of population in the surveyed settlements of Rivneregion in the year of study were formed at the expense of internal exposure doses ranging from 0.13 mSv · year-1 to0.32 mSv · year-1, which is below the criterion for radiologically contaminated territories. It has been establishedthat the incorporation of 137Cs by the inhabitants is a principal factor of the internal radiation dose formation. The 137Cs incorporation occurs through the consumption of such basic foodstuffs as milk and forest products, primarilymushrooms, which traditionally occupy a significant part of the diet in the Polissya area. The 137Cs content in thevast majority of milk and mushroom samples significantly exceeded the permissible levels (PL). The maximum con-tent of 137Cs in the collected milk samples was 384.7 Bq · L-1, which is 4 times higher than PL, and 36.9 kBq · kg-1 indried mushrooms being 15 times higher than PL. CONCLUSIONS: The existing radiation and ecological situation in the areas that were exposed to radioactive contam-ination as a result of the Chornobyl disaster requires the continuation of monitoring of levels of radioactive con-tamination of foodstuffs, especially collected in forests, and doses of radiation exposure of the population.

Pattern changes in quantitative and qualitative markers of hematopoietic stem cells during acute and chronic exposure to 90Sr isotope in cell culture. / ZAKONOMIRNOSTI ZMIN KIL'KISNYKh I IaKISNYKh POKAZNYKIV GEMOPOETYChNYKh STOVBUROVYKh KLITYN U KUL'TURI KLITYN V UMOVAKh DIi RADIONUKLIDU STRONTsIIu-90.

OBJECTIVE: The objective of our research was investigation of the hematopoietic system of laboratory rats under the influence of acute and chronic internal exposure to 90Sr isotope. MATERIALS AND METHODS: To study the condition of stem cells and their immediate progenitors we implemented cell culture methodology in vivo in gel diffusion capsules with subsequent analysis of the colonies and clusters. RESULTS: On the basis of experiments it was established that long-term effects of incorporated 90Sr isotope leads to significant disturbances in the hematopoietic system and in particular, revealing changes in hematological parameters of irradiated animals such as the appearance of circulating progenitor cells in peripheral blood, reducing the colony-forming efficiency of the bone marrow derived progenitor cells, as well as quantitative and qualitative changes in the clones. CONCLUSIONS: Indices confirm the connection of the detected effects in individuals exposed to ionizing radiation described in the earlier publications and can serve as basis for developing criteria for the formation of risk groups among people exposed to 90Sr.

Phase and structural transformations in metallic iron under the action of heavy ions and recoil nuclei.

By the use of various modes of Mössbauer spectroscopy after effects of irradiation of metal iron with (12)C(4+) and (14)N(5+) ions of medium energies, and alpha-particles and the (208)Tl, (208,212)Pb, and (216)Po recoil from a (228)Th-source have been studied. The experimental data obtained in the study enabled various types of external and internal radiation to be compared in regard to the damage they cause, as well as to their effect on the structure-, phase composition- and corrosion resistance properties of metallic iron. Irradiation with (12)C(4+) and (14)N(5+) ions is accompanied by both structural disordering of the α-Fe lattice, and the appearance of γ-phase in the bulk metal. This is indicated by a single line which is 2 to 3-fold broadened (as compared to the lines of the magnetic sextet). This is a result of a strong local heating of the lattice in the thermal spike area with a subsequent instant cooling-down and recrystallization of this "molted" area. Irradiation of iron foils with (12)C(4+)- and (14)N(5+) ions and with recoil nuclei does provoke corrosion processes (the formation of γ-FeOOH) and is accompanied by an intensive oxidation of the metal.

Peculiarities of internal radiation doses due to ¹³7Cs and 9°Sr intake in population from Zhytomyr oblast in a late period after the Chornobyl NPP accident.

STUDY OBJECTIVE: To reveal the peculiarities of internal radiation doses in the inhabitants of Zhytomyr oblast and to provide a scientific ground for arrangements on internal irradiation dose reducing in population from contaminated regions in long-term period after the ChNPP accident. MATERIALS AND METHODS: Comprehensive radiation monitoring was carried out in 4 settlements in Narodychi region of Zhytomyr oblast. The radiochemical, dosimetric methods (instrumental and numerical) were used in the study. RESULTS AND CONCLUSIONS: Significant (2-3.5 times) seasonal increase of incorporated ¹³7Cs level was revealed through a WBC-monitoring in residents (both for adults and children) of the supervised settlements of Narodytsky region, Zhytomyr oblast. The exceeding of 1.0 mSv x year⁻¹ dose was revealed in up to 5 % of inspected persons. The maximal registered in those settlements ¹³7Cs content of 350 kBq is the source of 10 mSv x year⁻¹ annual dose. ¹³7Cs content in milk samples from those settlements didn't change much during a year. Elevation of ¹³7Cs content exceeding the permissible level of 100 Bq x litre⁻¹ was found in ~30-50 % of milk samples from Narodychi and Selets villages, whereas in Motiyky and Khrystynivka villages the ¹³7Cs content didn't exceed permissible levels. 90Sr content both in potatoes and milk samples was much under the permissible level of 20 Bq x litre⁻¹. ¹³7Cs content in potato samples was under the permissible levels. It was found out that main part of internal irradiation doses in the settlements of concern is due to consumption of locally produced victuals i.e. milk and natural/forest-originated products like berries and mushrooms.

Radiation protection and health of personnel of contracting enterprises participating in works for transformation of the object "shelter" of SSE Chornobyl NPP into an ecologically safe system.

UNLABELLED: Transformation of the object "Shelter" (OS) of SSE Chornobyl NPP into an ecologically safe system is one of the most important state programs in Ukraine. Both medical and dosimetric measures on healthcare of personnel participating in these works ranks the main place among most actual problems of contemporary clinical radiobiology, radiation hygiene, and radiation protection. The study objective was to work out and implement the medical and biophysical checking of the health status and workability both with radiation protection of personnel executing works on transformation of OS into an ecologically safe system. MATERIALS AND METHODS. The interdependent complex program of medical and biophysical (for internal and external irradiation) control of personnel executing the production tasks under conditions of ionizing radiation impact and open sources of ionizing radiation. Realization of medical examination envisages the estimation of the status of haemopoietic, immune, endocrine, respiratory systems, organ of vision, nervous system, psychics status and psychophysiological adaptation, ear, both with circulatory, digestive, urogenital, and bone-muscular system. There were 19434 cases of medical control of personnel in total. RESULTS: Results of the input medical control testify to the following: 4698 (48.90%) were admitted to work, 4909 (51.10%) were rejected. Individual annual effective doses of irradiation in the major part of cases did not exceed 12 mSv. There were 1845 cases of 239+240Pu content in excrements exceeding the level of 1.5 mBq/sample at a current biophysical control. Individual doses of internal irradiation at that did not exceed 1 mSv. CONCLUSIONS: The program of medical and biophysical service for reconstruction works on the OS proved its necessity and efficiency as its results showed that under the unique radiation-hygienical conditions not engineering challenges and technical problems but issues of how to save the health and workability of people and prevent the overdose of personnel including due to an internal irradiation are most critical.