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000178296 041__ $$aEnglish
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000178296 1001_ $$0P:(DE-He78)08163497c53924f9edbd00f56b931672$$aBojcevski, Jovana$$b0$$eFirst author$$udkfz
000178296 245__ $$aAssessment of Normal Tissue Radiosensitivity by Evaluating DNA Damage and Repair Kinetics in Human Brain Organoids.
000178296 260__ $$aBasel$$bMolecular Diversity Preservation International$$c2021
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000178296 520__ $$aDNA-double strand break (DSB), detected by immunostaining of key proteins orchestrating repair, like γH2AX and 53BP1, is well established as a surrogate for tissue radiosensitivity. We hypothesized that the generation of normal brain 3D organoids ('mini-brains') from human induced pluripotent stem cells (hiPSC) combined with detection of DNA damage repair (DDR) may hold the promise towards developing personalized models for the determination of normal tissue radiosensitivity. In this study, cerebral organoids, an in vitro model that stands in its complexity between 2D cellular system and an organ, have been used. To quantify radiation-induced response, immunofluorescent staining with γH2AX and 53BP1 were applied at early (30 min, initial damage), and late time points (18 and 72 h, residual damage), following clinical standard 2 Gy irradiation. Based on our findings, assessment of DDR kinetics as a surrogate for radiosensitivity in hiPSC derived cerebral organoids is feasible. Further development of mini-brains recapitulating mature adult neuronal tissue and implementation of additional signaling and toxicity surrogates may pave the way towards development of next-generation personalized assessment of radiosensitivity in healthy neuronal tissue.
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000178296 650_7 $$2Other$$aDNA damage repair
000178296 650_7 $$2Other$$abrain organoids
000178296 650_7 $$2Other$$amini-brains
000178296 650_7 $$2Other$$aneurotoxicity
000178296 650_7 $$2Other$$aradiation
000178296 650_7 $$2Other$$aradiosensitivity
000178296 7001_ $$0P:(DE-He78)be724b82903aa397737196d8200edb30$$aWang, Changwen$$b1$$udkfz
000178296 7001_ $$0P:(DE-He78)76aeb2431f7458c9261e69c5420390c6$$aLiu, Haikun$$b2$$udkfz
000178296 7001_ $$0P:(DE-He78)360c5bc2b71a849e35aca747c041dda7$$aAbdollahi, Amir$$b3$$udkfz
000178296 7001_ $$0P:(DE-He78)e24b607ded082a3089a1f6bf326a7a8e$$aDokic, Ivana$$b4$$eLast author$$udkfz
000178296 773__ $$0PERI:(DE-600)2019364-6$$a10.3390/ijms222413195$$gVol. 22, no. 24, p. 13195 -$$n24$$p13195 $$tInternational journal of molecular sciences$$v22$$x1422-0067$$y2021
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