| 1. |
- Daşu, Alexandru, et al.
(författare)
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Inducible repair and intrinsic radiosensitivity: a complex but predictable relationship?
- 2000
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 153:3, s. 279-288
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Tidskriftsartikel (refereegranskat)abstract
- Two groups have proposed a simple linear relationship between inducible radioresistance in a variety of mammalian cells and their intrinsic radiosensitivity at 2 Gy (Lambin et al., Int.J. Radiat. Biol. 69, 279-290, 1996; Alsbeih and Raaphorst, unpublished results, 1997). The inducible repair response (IRR) is quantified as a ratio, alpha(S)/alpha(R), i.e. the slope in the hypersensitive low-dose region, alpha(S), relative to the alpha(R) term of the classical linear-quadratic formula. These proposals imply that the intrinsic radiosensitivity at clinically relevant doses is directly linked to the cell's ability to mount an adaptive response as a result of exposure to very low doses of radiation. We have re-examined this correlation and found that the more extensive data set now available in the literature does not support the contention of a simple linear relationship. The two parameters are correlated, but by a much more complex relationship. A more logical fit is obtained with a log-linear equation. A series of log-linear curves are needed to describe the correlation between IRR and SF2, because of the spectrum of alpha/beta ratios among the cell lines and hence the confounding effect of the beta term at a dose of 2 Gy. The degree of repair competence before irradiation starts could also be a major factor in the apparent magnitude of the amount of repair induced. There appears to be a systematic difference in the data sets from different series of cell lines that have been obtained using flow cytometry techniques in the laboratory in Vancouver and using dynamic microscope imaging at the Gray Laboratory. We suggest that the use of a brief exposure to a laser beam in flow cytometry before the cells are irradiated might itself partially induce a stress response and change the DNA repair capacity of the cells. The clinical consequences of the relationship for predicting the benefits of altered fractionation schedules are discussed. [ru5]
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| 2. |
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| 3. |
- Naumburg, Estelle, et al.
(författare)
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Intrauterine exposure to diagnostic X rays and risk of childhood leukemia subtypes
- 2001
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 156, s. 718-
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between childhood leukemia and prenatal exposure to low-dose ionizing radiation remains debatable. This population-based case-control study investigated the association between prenatal exposure to diagnostic X-ray examinations (for different types of examinations and at different stages of pregnancy) and the risk of childhood lymphatic and myeloid leukemia. All children born and diagnosed with leukemia between 1973-1989 in Sweden (578 lymphatic and 74 myeloid) were selected as cases, and each was matched (by sex and year of birth) to a healthy control child (excluding Down's syndrome). Exposure data were abstracted blindly from all available medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by conditional logistic regression. It was found that prenatal X-ray examinations resulting in direct fetal exposure were not associated with a significant overall increased risk for childhood leukemia (OR = 1.11, 95% CI 0.83-1.47), for lymphatic leukemia (OR = 1.04, 95% CI 0.77-1.40), or for myeloid leukemia (OR = 1.49, 95% CI 0.48-4.72). There was little evidence of a dose response or variation in risk by trimester of exposure or age at diagnosis. Thus X-ray examinations performed during pregnancy in the 1970s and 1980s in Sweden did not affect the risk of childhood leukemia discernibly.
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| 4. |
- Olsson, Sara, 1970-, et al.
(författare)
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EPR Dosimetric Properties of 2-Methylalanine : EPR, ENDOR and FT-EPR Investigations
- 2002
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 157:2, s. 113-121
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Tidskriftsartikel (refereegranskat)abstract
- To find an EPR dosimeter material that is sensitive enough for clinical use, the substance 2-methylalanine (2MA) with the chemical structure (CH3)2C(NH3+)COO− was tested for its sensitivity to ionizing radiation, dose response, and radical stability over time. At equal and moderate settings of microwave power and modulation amplitude, 2MA was found to be 70% more sensitive than l-α-alanine, which is the most common EPR dosimeter material today. The dose response is linear, at least in the dose range of interest (0.5–100 Gy), and the time-dependent variations in signal intensity are very small and may be corrected for easily. The energy dependence of the stopping power and energy absorption was calculated and was found to be similar to that of alanine. The dependence of the signal intensity on microwave power and modulation amplitude was investigated, and the optimal settings were found to be 25 mW (Bruker ER 4102ST) and 12 gauss, respectively. Single crystals of 2MA were analyzed using ENDOR and ENDOR-induced EPR to identify the radiation-induced radicals that formed. Only one radical, in which the amino group is detached from the original molecule, was identified. This radical is obviously dominating and is apparently the only one relevant for dosimetry purposes. The complete set of coupling parameters for three hyperfine couplings is reported. The power saturation properties and spectral line width are ruled by the relaxation times T1 and T2. To determine the relaxation times of 2MA, pulsed EPR experiments were performed on single crystals. Two different values of T1 were obtained, one in the range 1–3 µs, shown to be of importance for the dosimetry properties, and another that is strongly anisotropic with a value between 10 and 35 µs that does not seem to affect the saturation behavior. T2 was estimated to be of the order of 200–300 ns.
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| 5. |
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| 6. |
- Abramenkovs, Andris, et al.
(författare)
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Measurement of DNA-Dependent Protein Kinase Phosphorylation Using Flow Cytometry Provides a Reliable Estimate of DNA Repair Capacity
- 2017
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Ingår i: Radiation Research. - : RADIATION RESEARCH SOC. - 0033-7587 .- 1938-5404. ; 188:6, s. 597-604
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Tidskriftsartikel (refereegranskat)abstract
- Uncontrolled generation of DNA double-strand breaks (DSBs) in cells is regarded as a highly toxic event that threatens cell survival. Radiation-induced DNA DSBs are commonly measured by pulsed-field gel electrophoresis, microscopic evaluation of accumulating DNA damage response proteins (e.g., 53BP1 or gamma-H2AX) or flow cytometric analysis of gamma-H2AX. The advantage of flow cytometric analysis is that DSB formation and repair can be studied in relationship to cell cycle phase or expression of other proteins. However, gamma-H2AX is not able to monitor repair kinetics within the first 60 min postirradiation, a period when most DSBs undergo repair. A key protein in non-homologous end joining repair is the catalytic subunit of DNA-dependent protein kinase. Among several phosphorylation sites of DNA-dependent protein kinase, the threonine at position 2609 (T2609), which is phosphorylated by ataxia telangiectasia mutated (ATM) or DNA-dependent protein kinase catalytic subunit itself, activates the end processing of DSB. Using flow cytometry, we show here that phosphorylation at T2609 is faster in response to DSBs than gamma-H2AX. Furthermore, flow cytometric analysis of T2609 resulted in a better representation of fast repair kinetics than analysis of gamma-H2AX. In cells with reduced ligase IV activity, and wild-type cells where DNA-dependent protein kinase activity was inhibited, the reduced DSB repair capacity was observed by T2609 evaluation using flow cytometry. In conclusion, flow cytometric evaluation of DNA-dependent protein kinase T2609 can be used as a marker for early DSB repair and gives a better representation of early repair events than analysis of gamma-H2AX.
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| 7. |
- Adrian, Gabriel, et al.
(författare)
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Rescue Effect Inherited in Colony Formation Assays Affects Radiation Response
- 2018
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Ingår i: Radiation Research. - 0033-7587. ; 189:1, s. 44-52
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that nonirradiated cells can exhibit radiation damage (bystander effect), and recent findings have shown that nonirradiated cells may help protect irradiated cells (rescue effect). These findings call into question the traditional view of radiation response: cells cannot be envisioned as isolated units. Here, we investigated traditional colony formation assays to determine if they also comprise cellular communication affecting the radiation response, using colony formation assays with varying numbers of cells, modulated beam irradiation and media transfer. Our findings showed that surviving fraction gradually increased with increasing number of irradiated cells. Specifically, for DU-145 human prostate cancer cells, surviving fraction increased 1.9-to-4.1-fold after 5-12 Gy irradiation; and for MM576 human melanoma cells, surviving fraction increased 1.9-fold after 5 Gy irradiation. Furthermore, increased surviving fraction was evident after modulated beam irradiation, where irradiated cells could communicate with nonirradiated cells. Media from dense cell culture also increased surviving fraction. The results suggest that traditional colony formation assays comprise unavoidable cellular communication affecting radiation outcome and the shape of the survival curve. We also propose that the increased in-field surviving fraction after modulated beam irradiation is due to the same effect.
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| 8. |
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| 9. |
- Bajinskis, Ainars, et al.
(författare)
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Low-Dose/Dose-Rate gamma Radiation Depresses Neural Differentiation and Alters Protein Expression Profiles in Neuroblastoma SH-SY5Y Cells and C17.2 Neural Stem Cells
- 2011
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 175:2, s. 185-192
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Tidskriftsartikel (refereegranskat)abstract
- The effects of low doses of ionizing radiation on cellular development in the nervous system are presently unclear. The focus of the present study was to examine low-dose gamma-radiation-induced effects on the differentiation of neuronal cells and on the development of neural stem cells to glial cells. Human neuroblastoma SH-SY5Y cells were exposed to (137)Cs gamma rays at different stages of retinoic acid-induced neuronal differentiation, and neurite formation was determined 6 days after exposure. When SH-SY5Y cells were exposed to low-dose-rate gamma rays at the onset of differentiation, the number of neurites formed per cell was significantly less after exposure to either 10, 30 or 100 mGy compared to control cells. Exposure to 10 and 30 mGy attenuated differentiation of immature C17.2 mouse-derived neural stem cells to glial cells, as verified by the diminished expression of glial fibrillary acidic protein. Proteomic analysis of the neuroblastoma cells by 2D-PAGE after 30 mGy irradiation showed that proteins involved in neuronal development were downregulated. Proteins involved in cell cycle and proliferation were altered in both cell lines after exposure to 30 mGy; however, the rate of cell proliferation was not affected in the low-dose range. The radiation-induced attenuation of differentiation and the persistent changes in protein expression is indicative of an epigenetic rather than a cytotoxic mechanism. (C) 2011 by Radiation Research Society
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| 10. |
- Berger, Thomas, et al.
(författare)
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The MATROSHKA Experiment: Results and Comparison from Extravehicular Activity (MTR-1) and Intravehicular Activity (MTR-2A/2B) Exposure
- 2013
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Ingår i: Radiation Research. - 1938-5404 .- 0033-7587. ; 180:6, s. 622-637
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Tidskriftsartikel (refereegranskat)abstract
- Astronauts working and living in space are exposed to considerably higher doses and different qualities of ionizing radiation than people on Earth. The multilateral MATROSHKA (MTR) experiment, coordinated by the German Aerospace Center, represents the most comprehensive effort to date in radiation protection dosimetry in space using an anthropomorphic upper-torso phantom used for radiotherapy treatment planning. The anthropomorphic upper-torso phantom maps the radiation distribution as a simulated human body installed outside (MTR-1) and inside different compartments (MTR-2A: Pirs; MTR-2B: Zvezda) of the Russian Segment of the International Space Station. Thermoluminescence dosimeters arranged in a 2.54 cm orthogonal grid, at the site of vital organs and on the surface of the phantom allow for visualization of the absorbed dose distribution with superior spatial resolution. These results should help improve the estimation of radiation risks for long-term human space exploration and support benchmarking of radiation transport codes.
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