Radiation and Environmental Biophysics

Selenium does not affect radiosensitivity of breast cancer cell lines Abstract Supplementation with the antioxidant selenium is frequently performed in breast cancer patients to protect the normal tissue from radiation-induced side effects. However, concerns exist whether selenium also protects tumor cells from radiation-induced cell kill and thereby reduces the efficacy of radiotherapy. In this work, the effect of selenium administration on the radiosensitivity of breast cancer cells was evaluated in vitro. Physiological relevant selenium concentrations (70 and 140 µg/l) did not affect DNA double-strand breaks (γH2AX foci) after 4-Gy X-ray irradiation. Also apoptosis (caspase 3/7) after irradiation with 10 Gy was not influenced by selenium treatment in MDA-MB-231 and MCF7 cells. Most importantly, selenium supplementation did not impair the clonogenic survival of the breast cancer cell lines after irradiation (0, 2, 4, 6, 8 Gy). The data suggest that physiological relevant selenium concentrations administered in combination with radiation therapy do not deteriorate the efficacy of radiotherapy in breast cancer patients. However, randomized clinical trials comparing the effectiveness of radiotherapy and the associated side effects in patients with and without selenium supplementation are recommended.

Dose to the interventional radiologist in CTF-guided procedures Abstract The aim of this work was to assess the occupational dose received by an interventional radiologist (IR) during computed tomography fluoroscopy (CTF)-guided procedures; to identify the most exposed areas of the body including the hands and fingers; to suggest recommendations for individual monitoring; and to improve radiation safety of the practice. A total of 53 CTF-guided procedures were studied. Twelve whole-body dosimeters were worn by the IR in each procedure for the assessment of the personal dose equivalent, Hp(10), on the chest, waist, and back, both over and under the lead apron, as well as the personal dose equivalent, Hp(0.07), on both arms, knees, and feet. Special gloves with casings to fit extremity dosimeters were prepared to assess Hp(0.07) to the fingers. The measured chest dose values were higher than those on the waist and back; the dominant hand or the left side was the most exposed. In general, the ring, middle, and index fingers of the dominant hand were the most exposed (maximum in the 36–39 mSv range), while wrist dose was negligible compared to finger doses. Based on the results obtained the following recommendations are suggested: protective devices (lead aprons, thyroid shield, and goggles) should be worn; Hp(10) should be assessed at the chest level both above and below the lead apron; finger doses can be measured on the basis of each middle finger; the arm closer to the beam should be monitored; and finally, a wrist dosimeter will not provide useful information.

Impact of dimethyl sulfoxide on irradiation-related DNA double-strand-break induction, -repair and cell survival Abstract Dimethyl sulfoxide (DMSO) is an effective radical scavenger and, when added to cells, reduces the initial number of radiation-induced DNA double-strand breaks (DSB). The aim of this study was to investigate modification by DMSO of both DSB induction and DSB repair by means of pulsed-field gel electrophoresis (PFGE) as well as gamma-H2AX immunofluorescence staining. WiDr cells (human colon carcinoma provided by DKFZ) were incubated with 2% DMSO for 2 h (or mock-treated) prior to irradiation with varying X-ray doses and subsequent incubation for repair. Sample processing for PFGE analysis or counting of γ-H2AX foci was performed according to standard protocols. Effects on apoptosis induction and cell survival were investigated additionally by standard protocols. DMSO reduced DSB yield after 20–80 Gy measured by PFGE. A qualitatively similar result was found after low-dose irradiation (1 Gy) using γ-H2AX immunofluorescence staining. During incubation for repair, both DNA fragment rejoining (PFGE) as well as γ-H2AX foci removal occurred at a reduced rate when cells had been pre-treated with DMSO. But this effect was clearly more pronounced for the PFGE-analyzed double-strand breakage, particularly at early repair times. WiDr cells treated with DMSO (2%) showed a significantly increased clonogenic survival after irradiation doses above 8 Gy. Apoptosis rates were not changed by DMSO. The radio-protective effect of DMSO, well known from other PFGE studies, could be confirmed for the formation of γ-H2AX foci. DSB generated in the presence of DMSO were less rapidly repaired. DMSO showed radio-protective effects on clonogenic survival but not on apoptosis.

Comparison of results from indoor radon measurements using active and passive methods with those from mathematical modeling Abstract Computational fluid dynamics (CFD) has been used to simulate the distribution of indoor radon concentration in a naturally ventilated room. Finite volume method was employed in CFD code for the simulation of indoor radon. The simulation results were validated at 34 points in a matrix of two horizontal planes (y = 1.3 m and y = 2.1 m) using passive pinhole dosimeters and at six points using an active scintillation radon monitor. The CFD results were found to exhibit an excellent correlation with the measured values. It is concluded that CFD analysis is a powerful tool to visualize indoor radon distribution.

The effect of lycopene supplementation on radiation-induced micronuclei in mice reticulocytes in vivo Abstract Lycopene (LYC) is a natural pigment present in tomatoes and other red fruits and vegetables including red carrots, red peppers, watermelons, pink grapefruits, apricots, pink guavas, and papaya. There is some evidence that LYC may provide protection against mutations induced by ionizing radiation. The study aimed to investigate whether the genetic material of reticulocytes (RET) could be protected from radiation-induced damage by LYC. Mice were treated with LYC [0.15 mg/kg bodyweight (bw), 0.30 mg/kg bw], acute and fractionated irradiation (0.5 Gy, 1 Gy applied daily), or with both agents (0.5 Gy + 0.15 mg/kg bw LYC, 0.5 Gy + 0.30 mg/kg bw LYC, 1 Gy + 0.15 mg/kg bw LYC, 1 Gy + 0.30 mg/kg LYC). LYC supplementation was started at 24 h or 1 week after the first irradiation. Irradiation significantly enhanced the frequency of micronuclei (MN) in RET. LYC treatment at a dose of 0.15 mg/kg bw 24 h after starting fractionated radiation at 1 Gy significantly decreased (41–68%, p < 0.0125) the level of MN in peripheral blood and bone marrow RET. LYC supplementation at 0.30 mg/kg bw did not significantly alter the frequency of MN in peripheral blood, but significantly increased the frequency of bone marrow RET MN. LYC treatment on day 8 following the first radiation exposure showed results similar (92–117%, p > 0.24) to those obtained with irradiation alone. Lycopene may act as a radiomitigator but must be administered at low doses and as soon as possible after irradiation. Contrary, combined exposure with high doses of irradiation and LYC may enhance the mutagenic effect of irradiation.

Monte Carlo single-cell dosimetry using Geant4-DNA: the effects of cell nucleus displacement and rotation on cellular S values Abstract Investigation of biological effects of low-dose ionizing radiation at the (sub-) cellular level, which is referred to as microdosimetry, remains a major challenge of today's radiobiology research. Monte Carlo simulation of radiation tracks can provide a detailed description of the physical processes involved in dimensions as small as the critical substructures of the cell. Hereby, in the present study, microdosimetric calculations of cellular S values for mono-energetic electrons and six Auger-emitting radionuclides were performed in single-cell models of liquid water using Geant4-DNA. The effects of displacement and rotation of the nucleus within the cell on the cellular S values were studied in spherical and ellipsoidal geometries. It was found that for the examined electron energies and radionuclides, in the case of nucleus cross-absorption where the radioactivity is either localized in the cytoplasm of the cell or distributed on the cell surface, rotation of the nucleus within the cell affects cellular S values less than displacement of the nucleus. Especially, the considerable differences observed in S(nucleus ← cell surface) values between an eccentric and a concentric cell–nucleus configuration in spherical and ellipsoidal geometries (up to 63% and up to 44%, respectively) suggests that the approximation of concentricity should be used with caution, at least for localized irradiation of the cell membrane by an Auger-emitter in targeted radionuclide cancer therapy. The obtained results, which are based on a more realistic modeling of the cell than was done before, provide more accurate information about nuclear dose. This can be useful for theranostic applications.

Toxicity of high uranium doses in broilers and protection with mineral adsorbents Abstract The aim of this study was to determine the uranium distribution and histopathological changes in broiler organs (kidney, liver, and brain) and muscle after 7 days of contamination with high doses of uranyl nitrate hexahydrate (UN), and the protective efficiency of three different mineral adsorbents (organobentonite, organozeolite, and sepiolite). During the 7 days, the UN administration was 50 mg per day, and administration of adsorbents was 2 g per day immediately after UN. In control group where broilers received only UN, histopathological changes such as necrosis of intestinal villi, oedema, vacuolisation and abruption of epithelial cells in renal tubules, oedema and vacuolisation of the cytoplasm of hepatocytes, and dystrophic changes in the neurons of the medulla oblongata were observed. In contrast, when the adsorbents organobentonite, organozeolite, and sepiolite were administered, no histopathological changes were observed in liver and brain. The investigated adsorbents showed the highest protective effects in liver (80–92%), compared to the kidney (77–86%), brain (37–64%), and meat (31–63%).

Hypoxia inducible factor-1α/B-cell lymphoma 2 signaling impacts radiosensitivity of H1299 non-small cell lung cancer cells in a normoxic environment Abstract Hypoxia inducible factor-1α (HIF-1α) is a critical transcriptional factor for the response of cells to hypoxic microenvironment and its expression induces resistance of hypoxic non-small-cell lung cancer (NSCLC) cells to radiotherapy. This study investigated how the activation of HIF-1α/B-cell lymphoma 2 (BCL-2) signaling under normoxic conditions impacted radiosensitivity of NSCLC cells. The recombinant pcDNA3.0-EGFP plasmids with wild-type or mutant HIF-1α complementary DNA (cDNA) were transfected into H1299 cells, an NSCLC cell line, establishing two H1299 sublines with high expression of HIF-1α. Compared with the levels of HIF-1α and BCL-2 proteins in non-transfected cells, increased levels of both proteins were found in transfected cells. Moreover, the expression of HIF-1α in non-transfected cells induced by chloride cobalt (CoCl2), a commonly used mimetic hypoxia reagent, was concomitant with the enhancement of BCL-2 expression. Conversely, reduction of HIF-1α expression by an inhibitor decreased the levels of BCL-2 proteins. The results revealed that the stabilization and expression of HIF-1α promoted the accumulation of BCL-2 proteins in H1299 cells. Subsequent experiments showed that intracellular HIF-1α/BCL-2 signaling was triggered in a normoxic environment after H1299 cells were exposed to irradiation, causing an elevated radioresistance. In contrast, blockage of HIF-1α/BCL-2 signaling leads to an elevated radiosensitivity. Proliferation of cells assay showed that, under normoxic conditions, population doubling times (PDTs) of irradiated cells were prolonged by suppression of HIF-1α/BCL-2 signaling. It is, therefore, indicated that HIF-1α/BCL-2 signaling activated by ionizing radiation reduces the radiosensitivity of H1299 cells independent of the hypoxic environment.

99m Tc activity concentrations in room air and resulting internal contamination of medical personnel during ventilation–perfusion lung scans Abstract This paper presents the results of measurements of 99mTc activity concentrations in indoor air in a nuclear medicine department and resulting estimated 99mTc intake by medical personnel. 99mTc air activity measurements were conducted at the Nuclear Medicine Department, John Paul II Hospital, Krakow, Poland, during ventilation–perfusion SPECT lung scans. Technetium from the air was collected by means of a mobile aerosol sampler with a Petryanov filter operating at an average flow rate of 10 dm3 min−1. Measured activities ranged from 99 ± 11 to 6.1 ± 0.5 kBq m−3. The resulting daily average intake of 99mTc by medical staff was estimated to be 5.4 kBq, 4.4 kBq, 3.0 kBq and 2.5 kBq, respectively, for male technicians, female technicians, male nurses and female nurses. Corresponding annual effective doses were 1.6 µSv for technicians and 1 µSv for nurses. The highest equivalent dose values were determined for extrathoracic (ET) airways: 5 µSv and 10 µSv for nurses and technicians, respectively. It is concluded that estimated annual absorbed doses are over three orders of magnitude lower than the dose limit established in the Polish Atomic Law Act and in recommendations of the International Commission on Radiological Protection for medical staff.

Nuclear medicine: workplace monitoring and internal occupational exposure during a ventilation/perfusion single-photon emission tomography Abstract The administration of 99mTc-HDP to diagnose pulmonary thromboembolisms leads to the presence of 99mTc in the environment of a nuclear medicine department, which could pose a potential risk of internal contamination to medical staff. Therefore, air samples from the administration room, gamma camera room and corridor of such a department were taken for the purpose of performing a workplace monitoring program of the medical centre under study, with maximum activity values of 640 ± 30 kBq/m3, 1.5 ± 0.1 kBq/m3 and 54 ± 3 kBq/m3, respectively, being obtained. These results correspond to committed effective doses received by exposed employees, via inhalation, when one ventilation/perfusion single-photon emission tomography study was performed, of 0.7 μSv, 0.004 μSv and 0.2 μSv, respectively. As inhalation is the employees' main exposure pathway to radio-aerosols, the internal dose of the nuclear medicine department's medical staff was also evaluated via urine bioassay measurements. Nuclear medicine nurses showed the highest 99mTc activity in 24-h urine samples (2100 ± 130 Bq/day), resulting in a committed effective dose of 21 μSv for each diagnostic study performed. Even so, the performance of ventilation/perfusion diagnostic studies did not constitute a substantial radiological risk since the annual dose limit for exposed employees was not exceeded.

Alexandros Sfakianakis
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alsfakia@gmail.com