| 1. |
- Akuwudike, Pamela, et al.
(författare)
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Cell Type-Specific Patterns in the Accumulation of DNA Damage Following Multifractional Radiation Exposure
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 23:21
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Tidskriftsartikel (refereegranskat)abstract
- Predicting the risk of second malignant neoplasms is complicated by uncertainties regarding the shape of the dose–response relationship at high doses. Limited understanding of the competitive relationship between cell killing and the accumulation of DNA lesions at high doses, as well as the effects of other modulatory factors unique to radiation exposure during radiotherapy, such as dose heterogeneity across normal tissue and dose fractionation, contribute to these uncertainties. The aim of this study was to analyze the impact of fractionated irradiations on two cell systems, focusing on the endpoints relevant for cancer induction. To simulate the heterogeneous dose distribution across normal tissue during radiotherapy, exponentially growing VH10 fibroblasts and AHH-1 lymphoblasts were irradiated with 9 and 12 fractions (VH10) and 10 fractions (AHH-1) at 0.25, 0.5, 1, or 2 Gy per fraction. The effects on cell growth, cell survival, radiosensitivity and the accumulation of residual DNA damage lesions were analyzed as functions of dose per fraction and the total absorbed dose. Residual γH2AX foci and other DNA damage markers (micronuclei, nuclear buds, and giant nuclei) were accumulated at high doses in both cell types, but in a cell type-dependent manner. The competitive relationship between cell killing and the accumulation of carcinogenic DNA damage following multifractional radiation exposure is cell type-specific.
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| 2. |
- Brzozowska, Beata, et al.
(författare)
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Freeware tool for analysing numbers and sizes of cell colonies
- 2019
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Ingår i: Radiation and Environmental Biophysics. - : Springer Science and Business Media LLC. - 0301-634X .- 1432-2099. ; 58:1, s. 109-117
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Tidskriftsartikel (refereegranskat)abstract
- The clonogenic cell survival assay is a basic method to study the cytotoxic effect of radiation and chemical toxins. In large experimental setups, counting of colonies by eye is tiresome and prone to bias. Moreover, it is often interesting to quantify the size of individual colonies. Such analyses are largely facilitated by computerised image analysis systems. Although a number of such systems exist, they all focus on enumerating colonies and not on analysing the colony size. We have developed a new software package for both counting colonies and plotting their size distributions. The software called count and Plot HIstograms of Colony Size(countPHICS) consists of two parts: (1) a macro written for ImageJ which analyses computerised images of cell culture dishes or 6-well plates, counts colonies, estimates their size and saves the results in a text file; (2) a program written with QT Creator which reads the text file, plots histograms of colony size distribution and fits the best function. The full program is freely available at: http://www.fuw.edu.pl/similar to bbrzozow/FizMed/countPHICS.html. In conclusion, our new publically available software will facilitate colony counting and provide additional information on the colony growth rate, which is relevant especially for radiosensitisation studies.
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| 3. |
- Brzozowska, Beata, et al.
(författare)
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Monte Carlo Modeling of DNA Lesions and Chromosomal Aberrations Induced by Mixed Beams of Alpha Particles and X-Rays
- 2020
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Ingår i: Frontiers in Physics. - : Frontiers Media SA. - 2296-424X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Prediction of health risks associated with exposure to mixed beams of high- and low-linear energy transfer ionizing radiation is based on the assumption that the biological effect caused by mixed radiation equals the sum of effects resulting from the action of individual beam components. Experimental studies have demonstrated that the cellular effects in cells exposed to mixed radiations are higher than that calculated based on the assumption of additivity. The present work contains a comparative analysis of published results on chromosomal aberrations in human peripheral blood lymphocytes exposed to mixed beams of alpha particles and X-rays with computer simulations using the PARTRAC program based on Monte Carlo methods. PARTRAC was used to calculate the levels of DNA single-strand breaks (SSB) and double-strand breaks (DSB—both complex and simple) and the level of chromosomal aberrations. SSB and DSB yields were found to be additive. A synergistic effect was obtained at the level of chromosomal aberrations, being in good agreement with the experimental results. This result demonstrates that the synergistic action of mixed beams results from processing of SSB and DSB and not from their initial frequencies. The level of synergy was dependent on the composition of the mixed beam, with highest level at 50:50 ratio of alpha particles and X-rays.
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| 4. |
- Gałecki, Maciej, et al.
(författare)
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Precision of scoring radiation-induced chromosomal aberrations and micronuclei by unexperienced scorers
- 2019
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Ingår i: International Journal of Radiation Biology. - : Informa UK Limited. - 0955-3002 .- 1362-3095. ; 95:9, s. 1251-1258
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Dose assessment plays an important role in case of radiological accidents and can be performed by scoring structural changes of chromosome morphology induced in cells by ionizing radiation. The results of such a test are biased by scorer experience, therefore, simple to learn assays are recommended to be used when fast analysis of a large amount of data is needed. The aim of this study was to compare the performance of two radiobiological assays - chromosomal aberrations and micronuclei - by unexperienced scorers with the reference values generated by an expert.Materials and methods: Each participant of an EU-funded two-week radiobiology course was asked to score Chinese hamster ovary cells exposed to gamma radiation up to 4 Gy. The congruence of students' and expert's scores at each dose and the coherence of the dose-response curve parameters between the students were investigated.Results: Micronucleus test tended to be faster and easier to learn than scoring chromosomal aberrations. However, both assays carried out by inexperienced students showed reasonable dose-response curves.Conclusions: In the case of a large radiological accident involving many casualties, the unexperienced scorers would support the process of biodosimetric triage by cytogenetic biological dosimetry.
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| 5. |
- Tartas, Adrianna, et al.
(författare)
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Modeling of dose and linear energy transfer homogeneity in cell nuclei exposed to alpha particles under various setup conditions
- 2023
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Ingår i: International Journal of Radiation Biology. - : Informa UK Limited. - 0955-3002 .- 1362-3095. ; 99:8, s. 1248-1256
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Different alpha exposure setups are often used to study the relation between biological responses and LET. This study aimed to estimate the dose heterogeneity and uncertainty in four exposure setups using Geant4 and PARTRAC codes. The importance of the irradiation system characteristics was shown in the context of reporting experimental results, especially in radiobiological studies at the molecular level.Materials and methods: Geant4 was used to estimate the dose distributions in cells grown on a disk exposed to alpha particles penetrating from above and below. The latter setup was simulated without and with a collimator. PARTRAC was used for the validation of Geant4 simulations based on distributions of the number of alpha particles penetrating a round nucleus and the deposited energy.Results: The LET distributions obtained for simulated setups excluding the collimator were wide and non-Gaussian. Using a collimator resulted in a Gaussian LET distribution, but strongly reduced dose rate and dose homogeneity. Comparison between PARTRAC and Geant4 calculations for the cell nucleus exposed to alpha radiation showed an excellent agreement.Conclusions: The interpretation of results from radiobiological experiments with alpha particles should always cover the characteristics of the experimental setup, which can be done precisely with computational methods.
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| 6. |
- Tartas, Adrianna, et al.
(författare)
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The order of sequential exposure of U2OS cells to gamma and alpha radiation influences the formation and decay dynamics of NBS1 foci
- 2023
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Ingår i: PLOS ONE. - 1932-6203. ; 18:6
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Tidskriftsartikel (refereegranskat)abstract
- DNA double strand breaks (DSBs) are a deleterious form of DNA damage. Densely ionising alpha radiation predominantly induces complex DSBs and sparsely ionising gamma radiation-simple DSBs. We have shown that alphas and gammas, when applied simultaneously, interact in producing a higher DNA damage response (DDR) than predicted by additivity. The mechanisms of the interaction remain obscure. The present study aimed at testing whether the sequence of exposure to alphas and gammas has an impact on the DDR, visualised by live NBS1-GFP (green fluorescent protein) focus dynamics in U2OS cells. Focus formation, decay, intensity and mobility were analysed up to 5 h post exposure. Focus frequencies directly after sequential alpha -> gamma and gamma -> alpha exposure were similar to gamma alone, but gamma -> alpha foci quickly declined below the expected values. Focus intensities and areas following alpha alone and alpha -> gamma were larger than after gamma alone and gamma -> alpha. Focus movement was most strongly attenuated by alpha -> gamma. Overall, sequential alpha -> gamma exposure induced the strongest change in characteristics and dynamics of NBS1-GFP foci. Possible explanation is that activation of the DDR is stronger when alpha-induced DNA damage precedes gamma-induced DNA damage.
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