Web of Science: 12 cites, Scopus: 12 cites, Google Scholar: cites
Cell to Cell Variability of Radiation-Induced Foci : relation between Observed Damage and Energy Deposition
Gruel, Gaëtan (Institut de Radioprotection et de Sûreté Nucléaire (Fontenay aux Roses, França))
Villagrasa, Carmen (Institut de Radioprotection et de Sûreté Nucléaire (Fontenay aux Roses, França))
Voisin, Pascale (Institut de Radioprotection et de Sûreté Nucléaire (Fontenay aux Roses, França))
Clairand, Isabelle (Institut de Radioprotection et de Sûreté Nucléaire (Fontenay aux Roses, França))
Benderitter, Marc (Institut de Radioprotection et de Sûreté Nucléaire (Fontenay aux Roses, França))
Bottollier-Depois, Jean-François (Institut de Radioprotection et de Sûreté Nucléaire (Fontenay aux Roses, França))
Barquinero, Joan Francesc (Universitat Autònoma de Barcelona. Departament de Biologia Animal, de Biologia Vegetal i d'Ecologia)

Data: 2016
Resum: 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.
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: Article ; recerca ; Versió publicada
Matèria: Confocal microscopy ; DNA damage ; Ionizing radiation ; Cell cycle and cell division ; Photons ; Focal planes ; Endothelial cells ; Flow cytometry
Publicat a: PloS one, Vol. 11 Núm. 1 (January 2016) , p. 1-20, ISSN 1932-6203

DOI: 10.1371/journal.pone.0145786
PMID: 26727594

20 p, 1.8 MB

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