Isomeric fluorescence sensors for wide range detection of ionizing radiations

In order to achieve a wider range of ionizing radiations detection,novel fluorescence sensing materials have been developed that utilize the fluorescence enhancement phenomenon caused by the intramolecular photoinduced electron transfer(PET)effect.Two perylene diimide isomers PDI-P and PDI-B were designed and synthesized,and their molecular structures were characterized by high-resolution Fourier transform mass spectrometry(HRMS),nuclear magnetic resonance hydrogen and carbon spectroscopy(~1H and~(13)C NMR).The interaction between ionizing radiation and fluorescent molecules was simulated by HCl titration.The results show that combining PDIs and HCl can improve fluorescence through the retro-PET process.Despite the similarities in chemical structures,the fluorescent enhancement multiple of PDI-B with aromatic amine as electron donor is much higher than that of PDI-P with alkyl amine.In the direct irradiation experiments of ionizing radiation,the emission enhancement multiples of PDI-P and PDI-B are 2.01 and 45.4,respectively.Furthermore,density functional theory(DFT)and time-dependent density functional theory(TDDFT)calculations indicate that the HOMO and HOMO-1 energy ranges of PDI-P and PDI-B are 0.54 e V and 1.13 e V,respectively.A wider energy range has a stronger driving force on electrons,which is conducive to fluorescence quenching.Both femtosecond transient absorption spectroscopy(fs-TAS)and transient fluorescence spectroscopy(TFS)tests show that PDI-B has shorter charge separation lifetime and higher electron transfer rate constant.Although both isomers can significantly reduce LOD during PET process,PDI-B with aromatic amine has a wider detection range of 0.118—240 Gy due to its larger emission enhancement,which is a leap of three orders of magnitude.It breaks through the detection range of gamma radiation reported in existing studies,and provides theoretical support for the further study of sensitive and effective new materials for ionizing radiation detection.

Aurora A Kinase Plays a Key Role in Mitosis Skip during Senescence Induced by Ionizing Radiation

Objective To investigate the fate and underlying mechanisms of G2 phase arrest in cancer cells elicited by ionizing radiation(IR).Methods Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora A inhibitor MLN8237(MLN)and/or p21 depletion by small interfering RNA(si RNA).Cell cycle distribution was determined using flow cytometry and a fluorescent ubiquitin-based cell cycle indicator(FUCCI)system combined with histone H3 phosphorylation at Ser10(p S10 H3)detection.Senescence was assessed using senescence-associated-β-galactosidase(SA-β-Gal),Ki67,andγH2AX staining.Protein expression levels were determined using western blotting.Results Tumor cells suffered severe DNA damage and underwent G2 arrest after IR treatment.The damaged cells did not successfully enter M phase nor were they stably blocked at G2 phase but underwent mitotic skipping and entered G1 phase as tetraploid cells,ultimately leading to senescence in G1.During this process,the p53/p21 pathway is hyperactivated.Accompanying p21 accumulation,Aurora A kinase levels declined sharply.MLN treatment confirmed that Aurora A kinase activity is essential for mitosis skipping and senescence induction.Conclusion Persistent p21 activation during IR-induced G2 phase blockade drives Aurora A kinase degradation,leading to senescence via mitotic skipping.

3D-printed engineered bacteria-laden gelatin/sodium alginate composite hydrogels for biological detection of ionizing radiation

Nuclear safety is a global growing concern,where ionizing radiation(IR)is a major injury factor resulting in serious damage to organisms.The detection of IR is usually conducted with physical dosimeters;however,biological IR detection methods are deficient.Here,a living composite hydrogel consisting of engineered bacteria and gelatin/sodium alginate was 3D-printed for the biological detection of IR.Three strains of PrecA::egfp gene circuit-containing engineered Escherichia coli were constructed with IR-dependent fluorescence,and the DH5αstrain was finally selected due to its highest radiation response and fluorescence.Engineered bacteria were loaded in a series of gelatin/sodium alginate matrix hydrogels with different rheology,3D printability and bacterial applicability.A high-gelatin-content hydrogel containing 10%gelatin/1.25%sodium alginatewas optimal.The optimal living composite hydrogelwas 3D-printedwith the special bioink,which reported significant green fluorescence underγ-ray radiation.The living composite hydrogel provides a biological strategy for the detection of environmental ionizing radiation.

Protective effects of ferulic acid against ionizing radiation-induced oxidative damage in rat lens through activating Nrf2 signal pathway

AIM: To examine the protection of ferulic acid(FA) against ionizing radiation(IR)-induced lens injury in rats, as well as the underlying mechanisms.METHODS: FA(50 mg/kg) was administered to rats for 4 consecutive days before they were given 10 Gy γ-radiation, as well as for 3 consecutive days afterward. Two weeks after radiation, the eye tissues were collected. Histological alterations were evaluated by hematoxylineosin staining. Enzyme linked immunosorbent assay(ELISA) was utilized to assess the activities of glutathione reductase(GR) and superoxide dismutase(SOD), as well as the levels of glutathione(GSH) and malondialdehyde(MDA) in the lenses. The protein and m RNA levels of Bcl-2, caspase-3, Bax, heme oxygenase-1(HO-1), and glutamatecysteine ligase catalytic subunit(GCLC) were quantified using Western blot and quantitative reverse transcription polymerase chain reaction, respectively. With nuclear extracts, the nuclear factor erythroid-2 related factor(Nrf2) protein expressions in the nuclei were also measured.RESULTS: Rats exposed to IR showed lens histological alterations which could be alleviated by FA. FA treatment reversed apoptosis-related markers in IR-induced lens, as evidenced by lower levels of Bax and caspase-3 and higher level of Bcl-2. Furthermore, IR induced oxidative damage manifested by decreased GSH level, increased MDA level, and decreased SOD and GR activities. FA boosted nuclear translocation of Nrf2 and increased the expressions of HO-1 and GCLC to inhibit oxidative stress, as evidenced by an increase in GSH, a decrease in MDA, and an increase in GR and SOD activities.CONCLUSION: FA may work well in preventing and treating IR-induced cataract through promoting the Nrf2 signal pathway to attenuate oxidative damage and cell apoptosis.

The role of crm-1 in ionizing radiation-induced nervous system dysfunction in Caenorhabditis elegans

Ionizing radiation can cause changes in nervous system function.However,the underlying mechanism remains unclear.In this study,Coenorhabditis elegans(C.elegans)was irradiated with 75 Gy of ^(60)Co whole-body γ radiation.Behavioral indicators(head thrashes,touch avoidance,and foraging),and the development of dopaminergic neurons related to behavioral function,were evaluated to assess the effects of ionizing radiation on nervous system function in C.elegans.Various behaviors were impaired after whole-body irradiation and degeneration of dopamine neurons was observed.This suggests that 75 Gy of γ radiation is sufficient to induce nervous system dysfunction.The genes nhr-76 and crm-1,which are reported to be related to nervous system function in human and mouse,were screened by transcriptome sequencing and bioinformatics analysis after irradiation or sham irradiation.The expression levels of these two genes were increased after radiation.Next,RNAi technology was used to inhibit the expression of crm-1,a gene whose homologs are associated with motor neuron development in other species.Downregulation of crm-1 expression effectively alleviated the deleterious effects of ionizing radiation on head thrashes and touch avoidance.It was also found that the expression level of crm-1 was regulated by the nuclear receptor gene nhr-76.The results of this study suggest that knocking down the expression level of nhr-76 can reduce the expression level of crm-1,while down-regulating the expression level of crm-1 can alleviate behavioral disorders induced by ionizing radiation.Therefore,inhibition of crm-1 may be of interest as a potential therapeutic target for ionizing radiation-induced neurological dysfunction.

Radiation-Associated Cardiotoxicity during Breast Cancer Treatment with Ionizing Radiation

Introduction: Breast cancer is the most common cancer in women. The treatment of breast carcinoma has advanced in the last decade and nowadays there are treatment protocols for all stages of the disease. Depending on the histopathology and stage breast cancer is treated with surgery, chemotherapy and radiotherapy. Regarding radiation, the field of irradiation includes the chest wall in patients with mastectomy, or the breast glandular tissue in patients with conserving surgical approaches. It is often treated with radiation therapy with two opposing tangential fields, and when indicated supraclavicular lymph nodes have to be irradiated. In this case an additional anterior field is applied. The tangential as well as the other radiation beams have a potential damaging effect on the healthy surrounding tissues, particularly over the heart in the left breast irradiation and in the lungs as well. Material and Methods: The study included 25 patients with left breast carcinoma, all post surgery, treated with radiation therapy, with the Elekta accelerator at our department. For academic purpose the treatment plans were generated following two methods. The first one with two tangential opposite beams plus a supraclavicular beam. In this method the angles of the tangential internal and external create an angle that is equal to 180˚{310˚& 130˚};no further changes were made to the beam geometry. Even though this is not the best option from the dose distribution point of view, it is still the most applied method, probably because of the semplicity of it. For each patient, a second plan was generated using two opposite tangential beams plus the supraclavicular beam. The angles of the internal and external beam were changed from 1˚to 3˚, depending on the surface of the body, so that the resulting angle was 180˚± 3˚{310˚± 3˚& 130˚± 3˚} with the aim to adapt the beam geometry as much as possible to the shape of the thoracic wall and to spare the OAR-s. Results and Discussion: The data show that the dose in the organs at risk, in terms of dose percentage, is lower when the angles of the beams are changed with 1˚- 3˚, compared to the classic method where the internal and external angles equal 180˚. This dose is not only non-negligible but significant;for every angle change from 1˚to 3˚, there is a significant reduction in the integral dose in the radiated volume, expressed in percentage, up to 5%. Conclusion: In most centers, the radiation treatment of breast is realized with two tangential opposite beams, which usually are mirror beams, or in other words, the internal and external beam angles create an angle of 180˚{α + β = 180˚}. This is a simple method, which provides a good dose distribution, but leaves a relatively high dose in the organs at risk. This study shows the difference in the dose percentage in the heart and lung when the beam angles are changed adapting to the anatomy of the patient. Reducing these doses allows for better overall treatment and less longtime toxicity, particularly for the heart tissues.

Total Ionizing Dose Radiation Effects on MOS Transistors with Different Layouts

Both nMOS and pMOS transistors with two-edged and multi-finger layouts are fabricated in a standard commercial 0.6μm CMOS/bulk process to study their total ionizing dose （TID） radiation effects. The leakage current, threshold voltage shift, and transconductance of the devices are monitored before and after T-ray irradiation. Different device bias conditions are used during irradiation. The experiment results show that TID radiation effects on nMOS devices are very sensitive to their layout structures. The impact of the layout on TID effects on pMOS devices is slight and can be neglected.

Genotypic characteristics of resistant tumors to pre-operative ionizing radiation in rectal cancer

Due to a wide range of clinical response in patients un-dergoing neo-adjuvant chemoradiation for rectal cancer it is essential to understand molecular factors that lead to the broad response observed in patients receiving the same form of treatment.Despite extensive research in this field,the exact mechanisms still remain elusive.Data raging from DNA-repair to specific molecules lead-ing to cell survival as well as resistance to apoptosis have been investigated.Individually,or in combination,there is no single pathway that has become clinically applicable to date.In the following review,we describe the current status of various pathways that might lead to resistance to the therapeutic applications of ionizing radiation in rectal cancer.

Study of a Portable Experimental Set for the Monitoring of Ionizing Radiation in the Tropical Region of Brazil

The Geiger is a proportional counter that detects the ambient ionizing radiation using a sensor tube and an associated electronics that allows feeding the desired voltage to the tube and acquiring the data in a certain time interval. With a sensor tube of Chinese and Russian origin and associated electronics based on the Arduino system, an experimental set of very low cost and easy handling for the monitoring of the local environmental ionizing radiation was set up. The main objective of this work is to disseminate this very low cost technique for the environmental study in secondary schools in Brazil.

Dynamics of Environmental Ionizing Radiation between May to September 2016 in the Region of S^o Jos~ dos Campos, SP, Brazil

Measurements of gamma radiation （200 keV to 10 MeV） were performed between May 25 to September 30 2016 at ITA （Technological Institute of Aeronautics） in Sao Jose dos Campos, SP, Brazil. Detector and associated electronics were previously calibrated in the laboratory of ITA using radioactive sources Cs-137, Po-210 and Sr-90. These sources provide gamma-ray energies in 0.662 keV alpha particles of 5.4 MeV and 0.90 keV electrons, respectively. Detector is a scintillator Sodium Iodide activated with Thallium [NaI（Tl）] associated to a photomultiplier and electronic devices which gather, store, distribute and structure data so users can analyze them. During the period of May-September, the experimental set was installed in an open room on a tower 25 meters above the ground. Measurements indicated variations of ionizing radiation in function of dry weather, rain, cold fronts passes and presence of fog in the area; the sample time interval was minute by minute. This study discusses the analysis and the dynamics of how to measure meteorological parameters using an ionizing radiation system.

Effect of Ionizing Radiation on the Expression of p16, CyclinDI and CDK4 in Mouse Thymocytes and Splenocytes

Objective To investigate the effect of ionizing radiation on the expression of p16, CyclinDl, and CDK4 in mouse thymocytes and splenocytes. Methods Fluorescent staining and flow cytometry analysis were employed for the measurement of protein expression. Results In time course experiments, it was found that the expression of p16 protein was significantly increased at 8, 24, and 48 h for thymocytes (P<0.05, P<0.01, and P<0.05, respectively) and at 24 h for splenocytes (P<0.05) after whole body irradiation (WBI) with 2.0 Gy X-rays. However, the expression of CDK4 protein was significantly decreased from 8 h to 24 h for thymocytes (P<0.05,P<0.01) and from 8 h to 72 h for splenocytes (P<0.05-P<0.01). In dose effect experiments, it was found that the expression of p16 protein in thymocytes and splenocytes was significantly increased at 24 h after WBI with 1.0, 2.0, and 4.0 Gy (P<0.05-P<0.01), whereas the expression of CDK4 protein was significantly decreased with 2.0Gy for thymocytes (P<0.05) and 0.5-6.0 Gy for splenocytes (P<0.05-P<0.01). Results also showed that the expression of CyclinDl protein decreased markedly in both thymocytes and splenocytes after exposure. Conclusion The results indicate that the expression of p 16 protein in thymocytes and splenocytes can be induced by ionizing radiation, and the p16-CyclinD1/CDK4 pathway may play an important role for G1 arrest of thymocytes induced by X-rays.

Combination of genistein with ionizing radiation on andro-gen-independent prostate cancer cells

Aim: To study the effect of the combined use of genistein and ionizing radiation (IR) on prostate DU145 cancer cells. Methods: DU145, an androgen-independent human prostate cancer cell line, was used in the experiment. Clonogenic assay was used to compare the survival of DU145 cells after treatments with genistein alone and in combination with graded IR. Apoptosis was assayed by DNA ladder and TUNEL stain. Cell cycle alterations were observed by flow cytometry and related protein expressions by immunoblotting. Results: Clonogenic assay demonstrated that genistein, even at low to medium concentrations, enhanced the radiosensitivity of DU145 cells. Twenty-four hours after treatment with IR and/or genistein, apoptosis was mainly seen with genistein at high concentrations and was minimally related to IR. At 72 h, apoptosis also occurred in treatment with lower concentration of genistein, especially when combined with IR. While both IR and genistein led to G2/M cell cycle arrest, combination of them further increased the DU145 cells at G2/M phase. This Gz/M arrest was largely maintained at 72 h, accompanied by increasing apoptosis and hyperdiploid cell population. Cell-cycle related protein analysis disclosed biphasic changes in cyclin B1 and less dramatically cdc-2, but stably elevated p21cipl levels with increasing genistein concentrations. Conclusion: Genistein enhanced the radiosensitivity of DU145 prostate cancer cells. The mechanisms might be involved in the increased apoptosis, prolonged cell cycle arrest and impaired damage repair.

Effect of ionizing radiation on transcription of colorectal cancer MDR1 gene of HCT-8 cells

Objective:To discuss effect of ionizing radiation on transcription of colorectal cancer multidrug resistance(MDR) 1 gene of HCT-8 cells.Methods:Total RNA was extracted by guanidine thiocyanate one-step method.Northern blot was applied to detect transcription level of MDR1 gene.The expression of P-gp protein was detected by flow cytometry.Results:The expression of MDRl of normal colorectal cancer HCT-8 cells was low.It was increased by 8.35 times under stimulus with 2 Gy.When treated with low doses in advance,high expressed MDR was decreased significantly under 0.05,0.1 Gy,which was 69.00%,62.89%in 2 Cy group and 5.77 times,5.25 times in sham irradiation group.No obvious difference was detected between(0.2+2) Gy group and 2 Gy group.Compared with sham irradiation group,the percentage of P-gp positive cells after radiation of a high 2 Gy dose was increased significantly(P【0.01).When treated with high radiation dose following low radiation dose(0.05 Gy,0.1 Gy) in advance,the percentage of P-gp positive cells were also increased significantly.The percentage of P-gp positive cells were increased obviously in 0.2 Gy and 2 Gy groups.Compared with simple high radiation 2 Gy group,the percentage of P-gp positive cells was decreased significantly(P【0.05).Conclusions: Low radiation dose can reverse multidrug resistance of colorectal cancer cells caused by high radiation dose.

Surveying ionizing radiations in real time using a smartphone

Surveying ionizing radiations of the surrounding with a smartphone provides a low-cost and convenient utility for the general public. We developed a smartphone application(App) that uses the built-in camera with a CMOS sensor and a radiation signal extraction algorithm.After a calibration through a series of radiation exposures,the App could display radiation dose rate and cumulative dose in real time without requiring covering the camera lens. A smartphone with this App can be used as a fast survey tool for ionizing radiations.

Autophagic cell death induced by reactive oxygen species is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells

AIM To investigate whether autophagic cell death is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells, and to explore the underlying mechanism.METHODS Human hepatocellular carcinoma cells were treated with hyperthermia and ionizing radiation. MTT and clonogenic assays were performed to determine cell survival. Cell autophagy was detected using acridine orange staining and flow cytometric analysis, and the expression of autophagy-associated proteins, LC3 and p62, was determined by Western blot analysis. Intracellular reactive oxygen species(ROS) were quantified using the fluorescent probe DCFH-DA.RESULTS Treatment with hyperthermia and ionizing radiation significantly decreased cell viability and surviving fraction as compared with hyperthermia or ionizing radiation alone. Cell autophagy was significantly increased after ionizing radiation combined with hyperthermia treatment, as evidenced by increased formation of acidic vesicular organelles, increased expression of LC3 II and decreased expression of p62. Intracellular ROS were also increased after combined treatment with hyperthermia and ionizing radiation. Pretreatment with N-acetylcysteine, an ROS scavenger, markedly inhibited the cytotoxicity and cell autophagy induced by hyperthermia and ionizing radiation.CONCLUSION Autophagic cell death is involved in hyperthermic sensitization of cancer cells to ionizing radiation, and its induction may be due to the increased intracellular ROS.

Identification of Two Novel Mitochondrial DNA Deletions Induced by Ionizing Radiation

Abstract Objective We identify ionizing radiation-induced mitochondrial DNA （mtDNA） deletions in human lymphocytes and their distribution in normal populations. Methods Long-range polymerase chain reactions （PCR） using two pairs of primers specific for the human mitochondrial genome were used to analyze the lymphoblastoid cell line following exposure to 10 Gy 6~Co y-rays. Limited-condition PCR, cloning and sequencing techniques were applied to verify the mtDNA deletions detected with long-range PCR. Human peripheral blood samples were irradiated with 0, 2 and 6 Gy ^60Co y-rays, and real-time PCR analysis was performed to validate the mtDNA deletions. In order to know the distribution of mtDNA deletions in normal population, 222 healthy Chinese adults were also investigated. Results Two mtDNA deletions, a 7455-bp deletion （nt475-nt7929 in heavy strand） and a 9225-bp deletion （nt7714 -nt369 in heavy strand）, occurring between two 8-bp direct repeats, were identified in lymphoblastoid cells using long-range PCR, limited-condition PCR and sequencing. These results were also observed for ^60Co y-rays irradiated human peripheral blood cells. Conclusion Two novel mtDNA deletions, a 7455-bp deletion and a 9225-bp deletion, were induced by ionizing radiation. The rate of the mtDNA deletions within a normal population was related to the donors＇ age, but was independent of gender.

p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis

Objective To explore the role of p21 in ionizing radiation-induced changes in protein levels during the G2/M transition and long-term G2 arrest.Methods Protein expression levels were assessed by western blot in the human uveal melanoma 92-1 cells after treatment with ionizing radiation.Depletion of p21 was carried out by employing the siR NA technique.Cell cycle distribution was determined by flow cytometry combined with histone H3 phosphorylation at Ser28,an M-phase marker.Senescence was assessed by senescenceassociated-β-galactosidase（SA-β-gal） staining combined with Ki67 staining,a cell proliferation marker.Results Accompanying increased p21,the protein levels of G2/M transition genes declined significantly in 92-1 cells irradiated with 5 Gy of X-rays.Furthermore,these irradiated cells were blocked at the G2 phase followed by cellular senescence.Depletion of p21 rescued radiation-induced G2 arrest as demonstrated by the upregulation of G2/M transition kinases,as well as the high expression of histone H3 phosphorylated at Ser28.Knockdown of p21 resulted in entry into mitosis of irradiated 92-1 cells.However,cells with serious DNA damage failed to undergo cytokinesis,leading to the accumulation of multinucleated cells.Conclusion Our results indicated that p21 was responsible for the downregulation of G2/M transition regulatory proteins and the bypass of mitosis induced by irradiation.Downregulation of p21 by siR NA resulted in G2-arrested cells entering into mitosis with serious DNA damage.This is the first report on elucidating the role of p21 in the bypass of mitosis.

An investigation of ionizing radiation damage in different SiGe processes

Different SiGe processes and device designs are the critical influences of ionizing radiation damage. Based on the different ionizing radiation damage in SiGe HBTs fabricated by Huajie and an IBM SiGe process, quantitatively numerical simulation of ionizing radiation damage was carried out to explicate the distribution of radiation-induced charges buildup in KT9041 and IBM SiGe HBTs. The sensitive areas of the EB-spacer and isolation oxide of KT9041 are much larger than those of the IBM SiGe HBT, and the distribution of charge buildup in KT9041 is several orders of magnitude greater than that of the IBM SiGe HBT. The result suggests that the simulations are consistent with the experiment, and indicates that the geometry of the EB-spacer, the area of the Si/SiO2 interface and the isolation structure could be contributing to the different ionizing radiation damage.

Ionizing Radiation-Induced RPL23a Reduction Regulates Apoptosis via RPL11-MDM2-p53 Pathway in Mouse Spermatogonia

Objective The expression patterns of ribosomal large subunit protein 23 a(RPL23 a)in mouse testes and GC-1 cells were analyzed to investigate the potential relationship between RPL23 a expression and spermatogonia apoptosis upon exposure to X-ray.Methods Male mice and GC-1 cells were irradiated with X-ray,terminal dUTP nick end-labelling(TUNEL)was performed to detect apoptotic spermatogonia in vivo.Apoptotic rate and cell cycle phase of GC-1 cells were analyzed with flow cytometry.Protein interactions were detected by Immunoprecipitation and protein localization as studied by immunofluorescence.Immunoblotting and real-time PCR were applied to analyze to protein and gene expression.Results Ionizing radiation(IR)increased spermatogonia apoptosis,the expression of RPL11,MDM2 and p53,and decreased RPL23 a expression in mice spermatogonia in vivo and in vitro.RPL23 a knockdown weakened the interaction between RPL23 a and RPL11,leading to p53 accumulation.Moreover,knockdown and IR decreased RPL23 a that induces spermatogonia apoptosis via RPL23 a-RPL11-MDM2-p53 pathway in GC-1 cells.Conclusion These results suggested that IR reduced RPL23 a expression,leading to weakened the RPL23 a-RPL11 interactions,which may have activated p53,resulting in spermatogonia apoptosis.These results provide insights into environmental and clinical risks of radiotherapy following exposure to IR in male fertility.The graphical abstract was available in the web of www.besjournal.com.

Inhibition of Ciliogenesis Enhances the Cellular Sensitivity to Temozolomide and Ionizing Radiation in Human Glioblastoma Cells

Objective To investigate the function of primary cilia in regulating the cellular response to temozolomide(TMZ)and ionizing radiation(IR)in glioblastoma(GBM).Methods GBM cells were treated with TMZ or X-ray/carbon ion.The primary cilia were examined by immunostaining with Arl13 b andγ-tubulin,and the cellular resistance ability was measured by cell viability assay or survival fraction assay.Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride,the autophagy was measured by acridine orange staining assay.The DNA damage repair ability was estimated by the kinetic curve ofγH2 AX foci,and the DNAdependent protein kinase(DNA-PK)activation was detected by immunostaining assay.Results Primary cilia were frequently preserved in GBM,and the induction of ciliogenesis decreased cell proliferation.TMZ and IR promoted ciliogenesis in dose-and time-dependent manners,and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR.The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair.The interference of ciliogenesis reduced DNA-PK activation,and the knockdown of DNA-PK led to cilium formation and elongation.Conclusion Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.