Predicted ionisation in mitochondria and observed acute changes in the mitochondrial transcriptome after gamma irradiation: a Monte Carlo simulation and quantitative PCR study

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dc.contributor.authorKam, WWYen_AU
dc.contributor.authorMcNamara, ALen_AU
dc.contributor.authorLake, Ven_AU
dc.contributor.authorBanos, Cen_AU
dc.contributor.authorDavies, JBen_AU
dc.contributor.authorKuncic, Zen_AU
dc.contributor.authorBanati, RBen_AU
dc.date.accessioned2020-03-30T00:14:45Zen_AU
dc.date.available2020-03-30T00:14:45Zen_AU
dc.date.issued2013-11-01en_AU
dc.date.statistics2020-03-20en_AU
dc.description.abstractIt is a widely accepted that the cell nucleus is the primary site of radiation damage while extra-nuclear radiation effects are not yet systematically included into models of radiation damage. We performed Monte Carlo simulations assuming a spherical cell (diameter 11.5 μm) modelled after JURKAT cells with the inclusion of realistic elemental composition data based on published literature. The cell model consists of cytoplasm (density 1 g/cm3), nucleus (diameter 8.5 μm; 40% of cell volume) as well as cylindrical mitochondria (diameter 1 μm; volume 0.5 μm3) of three different densities (1, 2 and 10 g/cm3) and total mitochondrial volume relative to the cell volume (10, 20, 30%). Our simulation predicts that if mitochondria take up more than 20% of a cell's volume, ionisation events will be the preferentially located in mitochondria rather than in the cell nucleus. Using quantitative polymerase chain reaction, we substantiate in JURKAT cells that human mitochondria respond to gamma radiation with early (within 30 min) differential changes in the expression levels of 18 mitochondrially encoded genes, whereby the number of regulated genes varies in a dose-dependent but non-linear pattern (10 Gy: 1 gene; 50 Gy: 5 genes; 100 Gy: 12 genes). The simulation data as well as the experimental observations suggest that current models of acute radiation effects, which largely focus on nuclear effects, might benefit from more systematic considerations of the early mitochondrial responses and how these may subsequently determine cell response to ionising radiation. © 2013 Elsevier B.V.en_AU
dc.identifier.citationKam, W. W. Y., McNamara, A. L., Lake, V., Banos, C., Davies, J. B., Kuncic, Z., & Banati, R. B. (2013). Predicted ionisation in mitochondria and observed acute changes in the mitochondrial transcriptome after gamma irradiation: a Monte Carlo simulation and quantitative PCR study. Mitochondrion, 13(6), 736-742. doi:10.1016/j.mito.2013.02.005en_AU
dc.identifier.govdoc8776en_AU
dc.identifier.issn1567-7249en_AU
dc.identifier.issue6en_AU
dc.identifier.journaltitleMitochondrionen_AU
dc.identifier.pagination736-742en_AU
dc.identifier.urihttps://doi.org/10.1016/j.mito.2013.02.005en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/9302en_AU
dc.identifier.volume13en_AU
dc.language.isoenen_AU
dc.publisherElsevier B.V.en_AU
dc.subjectMitochondriaen_AU
dc.subjectElectromagnetic radiationen_AU
dc.subjectMonte Carlo Methoden_AU
dc.subjectRadiationsen_AU
dc.subjectPolymerase chain reactionen_AU
dc.subjectRNAen_AU
dc.subjectCytoplasmen_AU
dc.titlePredicted ionisation in mitochondria and observed acute changes in the mitochondrial transcriptome after gamma irradiation: a Monte Carlo simulation and quantitative PCR studyen_AU
dc.typeJournal Articleen_AU
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