Differential DNA repair pathway choice in cancer cells after proton- and photon-irradiation

Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
Andrea O FontanaMartin Pruschy

Abstract

Non-homologous end-joining (NHEJ) and homologous recombination (HR) contribute to the repair of irradiation-induced DNA double-strand breaks (DSBs). We investigated the impact of the two major DSB repair machineries for cellular survival of human tumor cells in response to proton- and photon-irradiation. DNA damage repair and cell survival were analyzed in wildtype, HR- and NHEJ-repair-compromised and pharmacologically DNA-PKcs-inhibited human tumor cells in response to clinically relevant, low-linear energy transfer proton- and 200-keV photon-irradiation. Pharmacological inhibition of DNA-PKcs strongly radiosensitized lung adenocarcinoma and glioblastoma cells to photon- but to a much lower extent to proton-irradiation. Enhanced radiosensitization correlated with strongly delayed repair kinetics with elevated amounts of γH2AX foci after photon-irradiation. Interestingly, we observed reduced phosphorylation of DNA-PKcs at Ser-2056 and Thr-2609 clusters after proton-irradiation compared to photon-irradiation. In contrast, A549 cells depleted of the RAD51 recombinase were markedly hypersensitive to proton-irradiation in comparison with control cells. Likewise, human BRCA2-deficient ovarian carcinoma cells were hypersensitive towa...Continue Reading

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Feb 24, 2016·Frontiers in Oncology·Kathryn D HeldAkihisa Takahashi
Sep 20, 2015·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·H Peter Rodemann, Stephan Bodis
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