Microdosimetric spread for cell-sized targets exposed to60Co,192Ir and125I sources

Villegas, Fernanda; Tilly, Nina; Ahnesjö, Anders

doi:10.1093/rpd/ncv200

Cited by 6 publications

(8 citation statements)

References 10 publications

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“…For n>20, the Poisson distribution can be approximated well by a normal distribution of mean value n and standard deviation √n [ 15 ]. This is true in this work because for 60 Co irradiation this condition is met in typical cell nucleus volumes for D> 0.2 Gy.…”

Section: Methodsmentioning

confidence: 99%

“…Accordingly, and knowing thatz 1 and SDz 1 are both functions of the volume, we can calculate the parameters k 1 and k 2 needed to express the relative standard deviation of the specific energy distribution of the 60 Co irradiation as a function of the macroscopic dose D and the volume of the target V [ 15 ]: …”

Section: Methodsmentioning

confidence: 99%

“…In this work, we used this relation and the k 1 and k 2 values obtained by Villegas et al . [ 15 ] to calculate the specific energy distributions expected in different volumes related to the endothelial cell population irradiated with the 60 Co source at the IRSN facility.…”

Section: Methodsmentioning

confidence: 99%

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Cell to Cell Variability of Radiation-Induced Foci: Relation between Observed Damage and Energy Deposition

et al. 2016

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Most studies that aim to understand the interactions between different types of photon radiation and cellular DNA assume homogeneous cell irradiation, with all cells receiving the same amount of energy. The level of DNA damage is therefore generally determined by averaging it over the entire population of exposed cells. However, evaluating the molecular consequences of a stochastic phenomenon such as energy deposition of ionizing radiation by measuring only an average effect may not be sufficient for understanding some aspects of the cellular response to this radiation. The variance among the cells associated with this average effect may also be important for the behaviour of irradiated tissue. In this study, we accurately estimated the distribution of the number of radiation-induced γH2AX foci (RIF) per cell nucleus in a large population of endothelial cells exposed to 3 macroscopic doses of gamma rays from 60Co. The number of RIF varied significantly and reproducibly from cell to cell, with its relative standard deviation ranging from 36% to 18% depending on the macroscopic dose delivered. Interestingly, this relative cell-to-cell variability increased as the dose decreased, contrary to the mean RIF count per cell. This result shows that the dose effect, in terms of the number of DNA lesions indicated by RIF is not as simple as a purely proportional relation in which relative SD is constant with dose. To analyse the origins of this observed variability, we calculated the spread of the specific energy distribution for the different target volumes and subvolumes in which RIF can be generated. Variances, standard deviations and relative standard deviations all changed similarly from dose to dose for biological and calculated microdosimetric values. This similarity is an important argument that supports the hypothesis of the conservation of the association between the number of RIF per nucleus and the specific energy per DNA molecule. This comparison allowed us to calculate a volume of 1.6 μm3 for which the spread of the specific energy distribution could explain the entire variability of RIF counts per cell in an exposed cell population. The definition of this volume may allow to use a microdosimetric quantity to predict heterogeneity in DNA damage. Moreover, this value is consistent with the order of magnitude of the volume occupied by the hydrated sugar-phosphate backbone of the DNA molecule, which is the part of the DNA molecule responsible for strand breaks.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Cell to Cell Variability of Radiation-Induced Foci: Relation between Observed Damage and Energy Deposition

et al. 2016

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“…As a first approach, microdosimetric quantities were calculated, such as the frequency distribution of the specific energy and the microdosimetric spread, which reflects the spread in specific energy per cell in an irradiated cell population, since these quantities could be of use to study the possible difference between radiation qualities in terms of RBE [43].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Radio-Induced Damage in Endothelial Cells Irradiated with 40 kVp, 220 kVp, and 4 MV X-rays by Means of Micro and Nanodosimetric Calculations

Tang

Bueno

Meylan³

et al. 2019

IJMS

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The objective of this work was to study the differences in terms of early biological effects that might exist between different X-rays energies by using a mechanistic approach. To this end, radiobiological experiments exposing cell monolayers to three X-ray energies were performed in order to assess the yields of early DNA damage, in particular of double-strand breaks (DSBs). The simulation of these irradiations was set in order to understand the differences in the obtained experimental results. Hence, simulated results in terms of microdosimetric spectra and early DSB induction were analyzed and compared to the experimental data. Human umbilical vein endothelial cells (HUVECs) were irradiated with 40, 220 kVp, and 4 MV X-rays. The Geant4 Monte Carlo simulation toolkit and its extension Geant4-DNA were used for the simulations. Microdosimetric calculations aiming to determine possible differences in the variability of the energy absorbed by the irradiated cell population for those photon spectra were performed on 10,000 endothelial cell nuclei representing a cell monolayer. Nanodosimetric simulations were also carried out using a computation chain that allowed the simulation of physical, physico-chemical, and chemical stages on a single realistic endothelial cell nucleus model including both heterochromatin and euchromatin. DNA damage was scored in terms of yields of prompt DSBs per Gray (Gy) and per giga (109) base pair (Gbp) and DSB complexity was derived in order to be compared to experimental data expressed as numbers of histone variant H2AX (γ-H2AX) foci per cell. The calculated microdosimetric spread in the irradiated cell population was similar when comparing between 40 and 220 kVp X-rays and higher when comparing with 4 MV X-rays. Simulated yields of induced DSB/Gy/Gbp were found to be equivalent to those for 40 and 220 kVp but larger than those for 4 MV, resulting in a relative biological effectiveness (RBE) of 1.3. Additionally, DSB complexity was similar between the considered photon spectra. Simulated results were in good agreement with experimental data obtained by IRSN (Institut de radioprotection et de sûreté nucléaire) radiobiologists. Despite differences in photon energy, few differences were observed when comparing between 40 and 220 kVp X-rays in microdosimetric and nanodosimetric calculations. Nevertheless, variations were observed when comparing between 40/220 kVp and 4 MV X-rays. Thanks to the simulation results, these variations were able to be explained by the differences in the production of secondary electrons with energies below 10 keV.

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“…22 The update included the correction of an erroneous overestimation of the mean free path for electrons and an erroneous ejection angle from ion interactions, respectively. All data in this paper are based on the corrected code which has been already applied in microdosimetric analysis 23,24 and energy deposition cluster pattern analysis 25,26 of brachytherapy sources.…”

Section: C Mc Simulated Tracks and The Determination Of Cluster Pamentioning

confidence: 99%

Energy deposition clustering as a functional radiation quality descriptor for modeling relative biological effectiveness

et al. 2016

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Microdosimetric spread for cell-sized targets exposed to⁶⁰Co,¹⁹²Ir and¹²⁵I sources

Cited by 6 publications

References 10 publications

Cell to Cell Variability of Radiation-Induced Foci: Relation between Observed Damage and Energy Deposition

Cell to Cell Variability of Radiation-Induced Foci: Relation between Observed Damage and Energy Deposition

Assessment of Radio-Induced Damage in Endothelial Cells Irradiated with 40 kVp, 220 kVp, and 4 MV X-rays by Means of Micro and Nanodosimetric Calculations

Energy deposition clustering as a functional radiation quality descriptor for modeling relative biological effectiveness

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