| 1. |
- Hellström, Nina, 1976, et al.
(author)
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Unique gene expression patterns indicate microglial contribution to neural stem cell recovery following irradiation.
- 2011
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In: Molecular and cellular neurosciences. - : Elsevier BV. - 1095-9327 .- 1044-7431. ; 46:4, s. 710-9
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Journal article (peer-reviewed)abstract
- Ionizing radiation results in damage to neural stem cells and reduced neurogenesis. The aim of the present study was to determine intrinsic and extrinsic factors that influence neural stem cell survival following irradiation, using qPCR. Gene expression of hippocampal and SVZ neurospheres were analyzed following irradiation, and results demonstrated that irradiated hippocampal and SVZ stem cells displayed similar gene expression profiles for intrinsic genes. Irradiated microglia (extrinsic factor) isolated from the SVZ exhibited increased gene expression of growth factors involved in stem cell maintenance, proliferation, and survival. However, microglial genes in the irradiated hippocampus responded less favorably with respect to stem cell recovery. This might explain the superior recovery of SVZ compared to hippocampal stem cells following in vivo irradiation. In addition, our results show that a combination of growth factors, which were upregulated in SVZ microglia, increased the proliferation and decreased cell death of irradiated neurospheres in vitro.
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| 2. |
- Lyckesvärd, Madeleine Nordén, et al.
(author)
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Alpha particle induced DNA damage and repair in normal cultured thyrocytes of different proliferation status.
- 2014
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In: Mutation research. Fundamental and molecular mechanisms of mutagenesis. - : Elsevier BV. - 1879-2871 .- 0027-5107. ; 765, s. 48-56
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Journal article (peer-reviewed)abstract
- Childhood exposure to ionizing radiation increases the risk of developing thyroid cancer later in life and this is suggested to be due to higher proliferation of the young thyroid. The interest of using high-LET alpha particles from Astatine-211 ((211)At), concentrated in the thyroid by the same mechanism as (131)I [1], in cancer treatment has increased during recent years because of its high efficiency in inducing biological damage and beneficial dose distribution when compared to low-LET radiation. Most knowledge of the DNA damage response in thyroid is from studies using low-LET irradiation and much less is known of high-LET irradiation. In this paper we investigated the DNA damage response and biological consequences to photons from Cobolt-60 ((60)Co) and alpha particles from (211)At in normal primary thyrocytes of different cell cycle status. For both radiation qualities the intensity levels of γH2AX decreased during the first 24h in both cycling and stationary cultures and complete repair was seen in all cultures but cycling cells exposed to (211)At. Compared to stationary cells alpha particles were more harmful for cycling cultures, an effect also seen at the pChk2 levels. Increasing ratios of micronuclei per cell nuclei were seen up to 1Gy (211)At. We found that primary thyrocytes were much more sensitive to alpha particle exposure compared with low-LET photons. Calculations of the relative biological effectiveness yielded higher RBE for cycling cells compared with stationary cultures at a modest level of damage, clearly demonstrating that cell cycle status influences the relative effectiveness of alpha particles.
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| 3. |
- Osato, Kazuhiro, et al.
(author)
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Apoptosis-inducing factor deficiency decreases the proliferation rate and protects the subventricular zone against ionizing radiation.
- 2010
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In: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 1
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Journal article (peer-reviewed)abstract
- Cranial radiotherapy in children often leads to progressive cognitive decline. We have established a rodent model of irradiation-induced injury to the young brain. A single dose of 8Gy was administered to the left hemisphere of postnatal day 10 (P10) mice. Harlequin (Hq) mice, carrying the hypomorphic apoptosis-inducing factor AIF(Hq) mutation, express 60% less AIF at P10 and displayed significantly fewer dying cells in the subventricular zone (SVZ) 6h after IR, compared with wild type (Wt) littermates. Irradiated cyclophilin A-deficient (CypA(-/-)) mice confirmed that CypA has an essential role in AIF-induced apoptosis after IR. Hq mice displayed no reduction in SVZ size 7 days after IR, whereas 48% of the SVZ was lost in Wt mice. The proliferation rate was lower in the SVZ of Hq mice. Cultured neural precursor cells from the SVZ of Hq mice displayed a slower proliferation rate and were more resistant to IR. IR preferentially kills proliferating cells, and the slower proliferation rate in the SVZ of Hq mice may, at least partly, explain the protective effect of the Hq mutation. Together, these results indicate that targeting AIF may provide a fruitful strategy for protection of normal brain tissue against the detrimental side effects of IR.
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| 4. |
- Swanpalmer, John, 1958, et al.
(author)
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Experimental investigation of the effect of air cavity size in cylindrical ionization chambers on the measurements in (60)Co radiotherapy beams.
- 2011
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In: Physics in medicine and biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 56:22, s. 7093-107
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Journal article (peer-reviewed)abstract
- In the late 1970s, Johansson et al (1978 Int. Symp. National and International Standardization of Radiation Dosimetry (Atlanta 1977) vol 2 (Vienna: IAEA) pp 243-70) reported experimentally determined displacement correction factors (p(dis)) for cylindrical ionization chamber dosimetry in (60)Co and high-energy photon beams. These p(dis) factors have been implemented and are currently in use in a number of dosimetry protocols. However, the accuracy of these factors has recently been questioned by Wang and Rogers (2009a Phys. Med. Biol. 54 1609-20), who performed Monte Carlo simulations of the experiments performed by Johansson et al. They reported that the inaccuracy of the p(dis) factors originated from the normalization procedure used by Johansson et al. In their experiments, Johansson et al normalized the measured depth-ionization curves at the depth of maximum ionization for each of the different ionization chambers. In this study, we experimentally investigated the effect of air cavity size of cylindrical ionization chambers in a PMMA phantom and (60)Co γ-beam. Two different pairs of air-filled cylindrical ionization chambers were used. The chambers in each pair had identical construction and materials but different air cavity volume (diameter). A 20 MeV electron beam was utilized to determine the ratio of the mass of air in the cavity of the two chambers in each pair. This ratio of the mass of air in each pair was then used to compare the ratios of the ionizations obtained at different depths in the PMMA phantom and (60)Co γ-beam using the two pairs of chambers. The diameter of the air cavity of cylindrical ionization chambers influences both the depth at which the maximum ionization is observed and the ionization per unit mass of air at this depth. The correction determined at depths of 50 mm and 100 mm is smaller than the correction currently used in many dosimetry protocols. The results presented here agree with the findings of Wang and Rogers' Monte Carlo simulations and show that the normalization procedure employed by Johansson et al is not correct.
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| 5. |
- Swanpalmer, John, 1958, et al.
(author)
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The effect of air cavity size in cylindrical ionization chambers on the measurements in high-energy radiotherapy photon beams-an experimental study.
- 2012
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In: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 57:14, s. 4671-81
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Journal article (peer-reviewed)abstract
- The present investigation is a continuation of a previous study on the effect of the diameter of the air cavity in cylindrical ionization chambers on perturbation correction factors. Measurements were made using high-energy radiotherapy photon beams (4, 6 and 15 MV) in a water phantom. Two different pairs of cylindrical ionization chambers were used. The chambers in each pair had identical materials and construction but different air cavity diameters. The same methods were employed as in our previous investigation. The diameter of the air cavity in cylindrical ionization chambers influences the mass ionization (themeasured ionization expressed per unit mass of air in the chamber air cavity) at the depth where the maximum ionization is observed and a normalization at this depth is therefore not correct. The corrections obtained at depths of 50 and 100mm in the phantom showed that the air cavity diameter in cylindrical ionization chambers has a greater effect on the perturbation effects than the photon beam quality. The corrections found at depths of 50 and 100mm are smaller than those currently used in dosimetry protocols.
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