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dc.contributor.authorAnoopkumar-Dukie, S
dc.contributor.authorConere, T
dc.contributor.authorSisk, GD
dc.contributor.authorAllshire, A
dc.date.accessioned2017-05-03T15:31:52Z
dc.date.available2017-05-03T15:31:52Z
dc.date.issued2009
dc.date.modified2010-01-27T04:25:54Z
dc.identifier.issn0007-1285
dc.identifier.doi10.1259/bjr/35746067
dc.identifier.urihttp://hdl.handle.net/10072/28471
dc.description.abstractOxygen-dependent radiosensitivity of tumour cells reflects direct oxidative damage to DNA, but non-nuclear mechanisms including signalling pathways may also contribute. Mitochondria are likely candidates because not only do they integrate signals from each of the main kinase pathways but mitochondrial kinases responsive to oxidative stress communicate to the rest of the cell. Using pharmacological and immunochemical methods, we tested the role of mitochondrial permeability transition (MPT) and the Bcl-2 proteins in oxygen-dependent radiosensitivity. Drug-treated or untreated cervical cancer HeLa, breast cancer MCF-7 and melanoma MeWo cell lines were irradiated at 6.2 Gy under normoxic and hypoxic conditions then allowed to proliferate for 7 days. The MPT blocker cyclosporin A (2 microM) strongly protected HeLa but not the other two lines against oxygen-dependent radiosensitivity. By contrast, bongkrekic acid (50 microM), which blocks MPT by targeting the adenine nucleotide transporter, had only marginal effect and calcineurin inhibitor FK-506 (0.1 microM) had none. Nor was evidence found for the modulation of oxygen-dependent radiosensitivity by Bax/Bcl-2 signalling, mitochondrial ATP-dependent potassium (mitoK(ATP)) channels or mitochondrial Ca(2+) uptake. In conclusion, calcineurin-independent protection by cyclosporin A suggests that MPT but not mitoK(ATP) or the mitochondrial apoptosis pathway plays a causal role in oxygen-dependent radiosensitivity of HeLa cells. Targeting MPT may therefore improve the effectiveness of radiotherapy in some solid tumours.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherBritish Institute of Radiology
dc.publisher.placeUnited Kingdom
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom847
dc.relation.ispartofpageto854
dc.relation.ispartofissue982
dc.relation.ispartofjournalBritish Journal of Radiology
dc.relation.ispartofvolume82
dc.rights.retentionY
dc.subject.fieldofresearchCell Development, Proliferation and Death
dc.subject.fieldofresearchBiochemistry and Cell Biology not elsewhere classified
dc.subject.fieldofresearchClinical Sciences
dc.subject.fieldofresearchcode060103
dc.subject.fieldofresearchcode060199
dc.subject.fieldofresearchcode1103
dc.titleMitochondrial modulation of oxygen-dependent radiosensitivity in some human tumour cell lines
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyGriffith Health, School of Pharmacy
gro.date.issued2009
gro.hasfulltextNo Full Text
gro.griffith.authorAnoopkumar-Dukie, Shailendra


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