Early Biomarkers Associated with P53 Signaling for Acute Radiation Injury

Accurate dose assessment within 1 day or even 12 h after exposure through current methods of dose estimation remains a challenge, in response to a large number of casualties caused by nuclear or radiation accidents. P53 signaling pathway plays an important role in DNA damage repair and cell apoptosis induced by ionizing radiation. The changes of radiation-induced P53 related genes in the early stage of ionizing radiation should compensate for the deficiency of lymphocyte decline and γ-H2AX analysis as novel biomarkers of radiation damage. Bioinformatic analysis was performed on previous data to find candidate genes from human peripheral blood irradiated in vitro. The expression levels of candidate genes were detected by RT-PCR. The expressions of screened DDB2, AEN, TRIAP1, and TRAF4 were stable in healthy population, but significantly up-regulated by radiation, with time specificity and dose dependence in 2–24 h after irradiation. They are early indicators for medical treatment in acute radiation injury. Their effective combination could achieve a more accurate dose assessment for large-scale wounded patients within 24 h post exposure. The effective combination of p53-related genes DDB2, AEN, TRIAP1, and TRAF4 is a novel biodosimetry for a large number of people exposed to acute nuclear accidents.

Methodological Approaches to Measurement of Carbon-14 for Control of its Radiation Impact on the Personnel and the Public

Purpose: Analysis of the current regulatory and methodological framework on control of doses from intake of 14C for the personnel and the public living in the control area of the nuclear power plant (NPP). Identifying the most informative methods of controlling radiation impact of 14C on a human being. Material and methods: Research literature on radiation impact of naturally occurring 14C; 14C entering the environment as a result of nuclear weapon tests; and 14C entering workplaces and the control area of NPP has been reviewed. Dose coefficients and other radiation characteristics of 14C provided in IAEA, ICRP and UNSCEAR publications have been summarized. Results: According to UNSCEAR, annual radiation burden caused by global 14C is the highest one (about 80 %) among radiation burdens associated with four critical naturally occurring cosmogenic radionuclides: 3H (0.01 µSv/year), 7Be (3.0 µSv/year), 14C (12 µSv/year) and 24Na (0.2µSv/year). The main way of 14C intake is the alimentary one when this isotope enters the human body with food. Dose from this kind of intake of global 14C can reach 40 µSv. The annual dose caused by aerogenic (inhalation) way of intake of global 14C does not exceed 1 µSv. The most informative methods of dose assessment for the personnel of NPP and the public living in the control area involve measurement of content of 14C in top soil, vegetation and food products. Conclusions: Significant amount of 14C enters the environment within the control area during operation of NPP, which causes the public radiation dose exceeding the dose from global 14C. The most informative objects characterizing content of technogenic 14C in the control area of NPP are top soil (humus) and vegetation. The liquid scintillation spectrometry involves sample preparation by burning of samples in oxygen with capturing of generated carbon dioxide and its transfer into organic solvent. This is the most technologically viable method for mass control of 14C content in samples of top soil and vegetation.

Circulating tRNA-Derived Small RNAs as Novel Radiation Biomarkers of Heavy Ion, Proton and X-ray Exposure

The effective and minimally invasive radiation biomarkers are valuable for exposure scenarios in nuclear accidents or space missions. Recent studies have opened the new sight of circulating small non-coding RNA (sncRNA) as radiation biomarkers. The tRNA-derived small RNA (tsRNA) is a new class of sncRNA. It is more abundant than other kinds of sncRNAs in extracellular vesicles or blood, presenting great potential as promising biomarkers. However, the circulating tsRNAs in response to ionizing radiation have not been reported. In this research, Kunming mice were total-body exposed to 0.05–2 Gy of carbon ions, protons, or X-rays, and the RNA sequencing was performed to profile the expression of sncRNAs in serum. After conditional screening and validation, we firstly identified 5 tsRNAs including 4 tRNA-related fragments (tRFs) and 1 tRNA half (tiRNA) which showed a significant level decrease after exposure to three kinds of radiations. Moreover, the radiation responses of these 5 serum tsRNAs were reproduced in other mouse strains, and the sequences of them could be detected in serum of humans. Furthermore, we developed multi-factor models based on tsRNA biomarkers to indicate the degree of radiation exposure with high sensitivity and specificity. These findings suggest that the circulating tsRNAs can serve as new minimally invasive biomarkers and can make a triage or dose assessment from blood sample collection within 4 h in exposure scenarios.

In Vivo Efficacy of Voriconazole in a Galleria mellonella Model of Invasive Infection Due to Azole-Susceptible or Resistant Aspergillus fumigatus Isolates

Aspergillus fumigatus is an environmental filamentous fungus responsible for life-threatening infections in humans and animals. Azoles are the first-line treatment for aspergillosis, but in recent years, the emergence of azole resistance in A. fumigatus has changed treatment recommendations. The objective of this study was to evaluate the efficacy of voriconazole (VRZ) in a Galleria mellonella model of invasive infection due to azole-susceptible or azole-resistant A. fumigatus isolates. We also sought to describe the pharmacokinetics of VRZ in the G. mellonella model. G. mellonella larvae were infected with conidial suspensions of azole-susceptible and azole-resistant isolates of A. fumigatus. Mortality curves were used to calculate the lethal dose. Assessment of the efficacy of VRZ or amphotericin B (AMB) treatment was based on mortality in the lethal model and histopathologic lesions. The pharmacokinetics of VRZ were determined in larval hemolymph. Invasive fungal infection was obtained after conidial inoculation. A dose-dependent reduction in mortality was observed after antifungal treatment with AMB and VRZ. VRZ was more effective at treating larvae inoculated with azole-susceptible A. fumigatus isolates than larvae inoculated with azole-resistant isolates. The concentration of VRZ was maximal at the beginning of treatment and gradually decreased in the hemolymph to reach a Cmin (24 h) between 0.11 and 11.30 mg/L, depending on the dose. In conclusion, G. mellonella is a suitable model for testing the efficacy of antifungal agents against A. fumigatus.

RADIATION SHIELDING AND DOSE ASSESSMENT OF THE CYCLOTRON FACILITY AT INRNE-BAS

The Institute for Nuclear Research and Nuclear Energy at the Bulgarian Academy of Sciences is working on the construction of a cyclotron centre. The facility is on a design level. At this stage of the project, an important task is the radiation shielding assessment of the facility. Nowadays, the Monte Carlo transport codes have become the tool of choice for solving this type of problem. In the current paper, the transport code FLUKA is used for the calculations. It is widely applied for shielding design and analysis of accelerators and their components. The distributions of the radiation fields inside and outside the cyclotron bunker are presented in this paper. Both different irradiation scenarios and bunker configurations are considered in the conducted Monte Carlo simulations. These results will be used as a guidance in site planning.

Radiation Dose Assessment of the Fog Lead Acrylic Shields during Coronary Angiography: A Phantom Study

This study aimed to evaluate the effects of fogging on the effectiveness of a lead glass shield in protecting an operator from radiation exposure during conventional coronary angiography (CAG). Optically stimulated luminescence dosimeters (OSLDs) were used to measure the effects of fogged lead glass shields (FLSs) and clear lead glass shields (CLSs) on the radiation doses of a cardiac catheterization surgeon. We simulated the scatter radiation incident on the operator with five angiographic projections with 10-s exposures. Experiments were conducted with a field of view of 25 cm, maximum of 100 cm between the X-ray tube and image intensifier, and 80 cm between the image intensifier and operator. Lead glass fogging had no significant effect at any angiographic projection. The average dose at the lens of the eye, thyroid glands, and gonads did not differ significantly between FLS and CLS. Although most surgeons view ceiling-suspended shields as hindrances during surgical procedures, the radiation dose at the operator’s eyes and thyroid glands increased by 13 and 10 times without the shield. The fogging of the shield is probably caused by post-surgery UV decontamination or detergents. An operator has no cause for concern regarding the radiation protection afforded by an FLS during CAG procedures.

PRELIMINARY EVALUATION OF PATIENT RADIATION DOSES DURING RADIONUCLIDE DIAGNOSTIC WITH MONOCLONAL ANTIBODIES LABELED WITH 89Zr

In connection with the constantly increasing use of monoclonal antibodies labeled with 89Zr, in clinical practice, it is urgent to study their pharmacokinetics with the determination, based on the data obtained, of absorbed doses in tumor foci, as well as intact organs and tissues, and effective doses of patients. To date, there are a limited number of studies that provide patient doses for diagnostic examinations using 89Zr-labeled monoclonal antibodies. In this regard, the purpose of this work was to assess the biodistribution of various monoclonal antibodies (ramucirumab, trastuzumab, atezolizumab) labeled with 89Zr, based on published data, with subsequent calculation of absorbed doses in radiosensitive organs and tissues and effective doses of patients. Based on the analysis of experimental data on the biodistribution of monoclonal antibodies labeled with 89Zr for the diagnosis of oncological diseases from the available literature sources and our own assessments, it has been concluded that the results of the determination of absorbed in organs and tissues and effective doses are inconsistent. The absorbed doses in organs, according to different literature sources, vary up to an order of magnitude within one organ and reach 440 mGy per examination, the effective dose varies from 3 to 112 mSv per examination. This may be due to differences in study design, radiometry and dose assessment methods. Comparison with doses obtained on the basis of a general model of biodistribution of monoclonal antibodies demonstrates the possibility of using this model for a rough estimate of internal doses of patients. However, for a more accurate assessment, it is necessary to standardize approaches to the determination of internal radiation doses using the most effective methodological solutions and software products.

REVIEW OF METHODIC INSTRUCTIONS AND RECOMMENDATIONS FOR EVALUATION OF ANNUAL EFFECTIVE DOSE TO HUMAN BEING IN CASES OF LIVING AT RADIOACTIVE CONTAMINATED AREAS

The proposed paper provides a review of recommendations, methodic instructions and software for evaluation of exposure doses to population domiciling radioactive contaminated territories. There is a review of dose calculation methods which are most common in neighbouring countries and beyond. The paper presents basic approaches, factors required for dose assessment with review of main pathways for artificial radionuclides intake. It addresses the need to develop methodic instructions and software for the cases of people living at Semipalatinsk test site area.