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Title: Hypersensitivity of BRCA1 heterozygote lymphoblastoid cells to gamma radiation and PARP inhibitors
Authors: Bourton, EC
Foster, HA
Plowman, PN
Harvey, AJ
Parris, C
Keywords: BRCA1;BRCA2;Heterozygote;Radiosensitivity;PARP inhibitor
Issue Date: 2013
Publisher: OMICS Publishing Group
Citation: Journal of Genetic Syndroms and Gene Therapy, 4(5), Article number 1000146, 2013
Abstract: PARP inhibitors can be used to induce synthetic lethality in cells with bi-allelic BRCA1 and BRCA2 mutations. However the effect of PARP inhibitors in combination with radiation on cells with mono-allelic mutations of BRCA1 and BRCA2 is unknown. We have examined the cell survival response of lymphoblastoid cells derived from normal individuals and those derived from carriers of BRCA1 and BRCA2 mutations, following exposure to ionising radiation and the PARP inhibitor Olaparib. Two lymphoblastoid cell lines from normal individuals and three with mono-allelic mutations in BRCA1 and BRCA2 were exposed to increasing doses of gamma radiation either alone or in combination with 5 μM Olaparib. Cell survival was measured using the MTT assay. Exposure to increasing doses of gamma radiation caused a reduction in cell survival of all cell types. The combined exposure to gamma radiation and 5 μM Olaparib did not enhance cell kill in normal or BRCA2 heterozygote lymphoblastoid cells but significantly enhanced cell kill in cells derived from BRCA1 carriers (P = 0.02). The treatment of cancer patients carrying mutations in the BRCA1 gene with radiotherapy and the PARP inhibitor Olaparib may significantly enhance radiation induced normal tissue toxicity in these patients.
Description: This article is made available through the Brunel Open Access Publishing Fund. Copyright @ 2013 Bourton EC, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ISSN: 2157-7412
Appears in Collections:Biological Sciences
Brunel OA Publishing Fund
Dept of Life Sciences Research Papers

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