SU-FF-T-487: Saturation of Repair Model for Cell Survival Applied to X-Ray and Carbon-Ion Irradiation

ABSTRACTPurposeTo develop an empirical model to predict radiosensitivity and relative biological effectiveness (RBE) after helium (He) and carbon (C) ion irradiation with or without DNA repair inhibitors.MethodsWe characterized survival in eight human cancer cell lines exposed to 6 MV photons and to He- and C-ions with linear energy transfer (LET) values of 2.2-60.5 keV/μm to verify that the radiosensitivity parameters (D5%, D10%, D20%, D37%, D50% and SF2Gy) correlate linearly between photon and ion radiation with or without DNA-PKcs or ATR inhibitors. Then, we parameterized the LET response of the parameters governing these linear correlations up to LET values of 225 keV/μm using the data in the Particle Irradiation Data Ensemble (PIDE) v3.2 database, creating a model that predicts a cell’s ion radiosensitivity, RBE and ion survival curve for a given LET on the basis of the cell’s photon radiosensitivity. We then trained this model using the PIDE database as a training dataset, and validated it by predicting the radiosensitivity of the cell lines we exposed to He- and C- ions with LET ranging from 2.2-60.5 keV/μm.ResultsRadiosensitivity to ions depended linearly with radiosensitivity of photons in the range of investigated LET values and the slopes and intercepts of these linear relationships within the PIDE database vary exponentially and linearly, respectively. Our model predicted ion radiosensitivity (e.g., D10%) within 5.1–21.3%, RBED10% within 5.0-17.1%, and ion mean inactivation dose within 6.7-25.1% for He- and C-ion LET ranging from 2.2-60.5 keV/μm.ConclusionsRadiosensitivity to He- and C-ions depend linearly with radiosensitivity to photons and can be used to predict ion radiosensitivity, RBE and cell survival curves for clinically relevant LET values from 2.2–60.5 keV/μm, with or without drug treatment.SUMMARYWe present a new empirical model capable of predicting clonogenic cell survival of cell lines exposed to helium and carbon ion beams. Our model is based on an observed linear correlation between radiosensitivity to ions and photons across a wide range of LET values. This linear correlation can be used to predict ion RBE, radiosensitivity, and the cell survival curve for a given LET all based on a cell’s photon survival curve.

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A COMPARISON BETWEEN X-RAY AND CARBON ION IRRADIATION IN HUMAN NEURAL STEM CELLS

Radiation Protection Dosimetry ◽

10.1093/rpd/ncy231 ◽

2018 ◽

Vol 183 (1-2) ◽

pp. 102-106 ◽

Cited By ~ 4

Author(s):

J Morini ◽

G Babini ◽

S Barbieri ◽

G Baiocco ◽

M Ciocca ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Ion Irradiation ◽

Carbon Ion ◽

X Ray ◽

Human Neural Stem Cells

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PU-H71, a novel Hsp90 inhibitor, as a potential cancer-specific sensitizer to carbon-ion beam therapy

Journal of Radiation Research ◽

10.1093/jrr/rrw054 ◽

2016 ◽

Vol 57 (5) ◽

pp. 572-575 ◽

Cited By ~ 11

Author(s):

Huizi Keiko Li ◽

Yoshitaka Matsumoto ◽

Yoshiya Furusawa ◽

Tadashi Kamada

Keyword(s):

Protein Expression ◽

Cell Line ◽

Ion Irradiation ◽

Ion Beam ◽

Hsp90 Inhibitor ◽

Osteosarcoma Cell ◽

Carbon Ion ◽

X Ray ◽

Carbon Ion Beam ◽

Recombination Pathway

Abstract PU-H71, a heat shock protein 90 (Hsp90) inhibitor, has yielded therapeutic efficacy in many preclinical models and is currently in clinical trials. Carbon-ion radiotherapy (CIRT) has provided successful tumor control; however, there is still room for improvement, particularly in terms of tumor-specific radiosensitization. The Hsp90 inhibitor PU-H71 has been shown to sensitize tumor cells to X-ray radiation. A murine osteosarcoma cell line (LM8) and a normal human fibroblast cell line (AG01522) were treated with PU-H71 before X-ray, 14- or 50-keV/µm carbon-ion beam (C-ion) irradiation. Cell survival and protein expression were evaluated with colony formation and western blot, respectively. Treatment with PU-H71 alone was shown to be non-toxic to both cell lines; however, PU-H71 was shown to significantly sensitize LM8 cells to not only X-ray, but also to C-ion irradiation, while only a minimal sensitizing effect was observed in AG01522 cells. PU-H71 treatment was found to suppress the protein expression levels of Rad51 and Ku70, which are associated with the homologous recombination pathway and the non-homologous end-joining pathway of double-strand break repair. The findings reported here suggest that PU-H71 could be a promising radiosensitizer for CIRT.

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Silencing of the lncRNA H19 enhances sensitivity to X-ray and carbon-ions through the miR-130a-3p /WNK3 signaling axis in NSCLC cells

Cancer Cell International ◽

10.1186/s12935-021-02268-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xueshan Zhao ◽

Xiaodong Jin ◽

Qiuning Zhang ◽

Ruifeng Liu ◽

Hongtao Luo ◽

...

Keyword(s):

Cell Lines ◽

Therapeutic Target ◽

Ion Irradiation ◽

Expression Profiles ◽

Expression Patterns ◽

Nsclc Cell ◽

Luciferase Reporter ◽

Antitumor Effects ◽

Carbon Ion ◽

X Ray

Abstract Background The lncRNA H19 is believed to act as an oncogene in various types of tumors and is considered to be a therapeutic target and diagnostic marker. However, the role of the lncRNA H19 in regulating the radiosensitivity of non-small cell lung cancer (NSCLC) cells is unknown. Methods The expression profiles of lncRNAs in NSCLC were explored via transcriptome sequencing. CCK-8, EdU incorporation and clonogenic survival assays were conducted to evaluate the proliferation and radiosensitivity of NSCLC cells. Flow cytometry and Western blotting were conducted to measure the level of apoptosis. The binding relationship between the lncRNA H19 and miR-130a-3p was determined by a dual-luciferase reporter assay. A binding relationship was also identified between miR-130a-3p and With-No-Lysine Kinase 3 (WNK3). Results Expression patterns of lncRNAs revealed that the lncRNA H19 was upregulated in radioresistant NSCLC (A549-R11) cells compared with A549 cells. Knockdown of the lncRNA H19 enhanced the sensitivity of NSCLC cell lines to X-ray and carbon ion irradiation. Mechanistically, the lncRNA H19 serves as a sponge of miR-130a-3p, which downregulates WNK3 expression. The lncRNA H19–miR-130a-3p–WNK3 axis modulates radiosensitivity by regulating apoptosis in NSCLC cell lines. Conclusion Knockdown of the lncRNA H19 promotes the sensitivity of NSCLC cells to X-ray and carbon ion irradiation. Hence, the lncRNA H19 might function as a potential therapeutic target that enhances the antitumor effects of radiotherapy in NSCLC.

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Genetic Effects of X-Ray and Carbon Ion Irradiation in Head and Neck Carcinoma Cell Lines

The Bulletin of Tokyo Dental College ◽

10.2209/tdcpublication.48.177 ◽

2007 ◽

Vol 48 (4) ◽

pp. 177-185 ◽

Cited By ~ 6

Author(s):

Nobuharu Yamamoto ◽

Chihaya Ikeda ◽

Takashi Yakushiji ◽

Takeshi Nomura ◽

Akira Katakura ◽

...

Keyword(s):

Head And Neck ◽

Cell Lines ◽

Carcinoma Cell ◽

Ion Irradiation ◽

Head And Neck Carcinoma ◽

Genetic Effects ◽

Carbon Ion ◽

X Ray ◽

Carcinoma Cell Lines ◽

Neck Carcinoma

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Effects of carbon ion irradiation and X-ray irradiation on the ubiquitylated protein accumulation

International Journal of Oncology ◽

10.3892/ijo.2016.3504 ◽

2016 ◽

Vol 49 (1) ◽

pp. 144-152 ◽

Cited By ~ 1

Author(s):

TETSURO ISOZAKI ◽

MAYUMI FUJITA ◽

SHIGERU YAMADA ◽

KAORI IMADOME ◽

YOSHIMI SHOJI ◽

...

Keyword(s):

Ion Irradiation ◽

Protein Accumulation ◽

Carbon Ion ◽

X Ray ◽

Ubiquitylated Protein

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Carbon ion irradiation abrogates Lin28B-induced X-ray resistance in melanoma cells

Journal of Radiation Research ◽

10.1093/jrr/rrx022 ◽

2017 ◽

Vol 58 (6) ◽

pp. 765-771 ◽

Cited By ~ 4

Author(s):

Seong-Joon Park ◽

Kyu Heo ◽

Chulwon Choi ◽

Kwangmo Yang ◽

Akiko Adachi ◽

...

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Melanoma Cell ◽

Ion Irradiation ◽

Ion Beam ◽

Melanoma Cells ◽

Micro Rna ◽

Carbon Ion ◽

X Ray ◽

Melanoma Cell Lines

Abstract The Lin28/let-7 axis plays an important role in tumor initiation and developmental processes. Lin28B is upregulated in a variety of cancers, and its overexpression enhances cancer cell proliferation and radioresistance through the suppression of let-7 micro RNA expression. In this study, we investigated the role of the Lin28/let7 axis as a target for radiosensitization of melanoma cancer cells. The overexpression of Lin28B reduced mature let-7 microRNA expression in melanoma cell lines, and enhanced the sphere-forming ability of melanoma cell lines, which is a characteristic of cancer stem cell (CSC) populations. Interestingly, Lin28B-overexpressed melanoma cells were more resistant to X-ray irradiation than control cells, and Lin28B-induced radioresistance was abolished after carbon ion irradiation. Consistent with these results, Lin28B overexpression reduced the numbers of γH2A.X foci after X-ray irradiation, whereas carbon ion irradiation had no such effect. Our results suggest that a carbon ion beam is more effective than an X-ray beam in terms of killing cancer cells, possibly due to elimination of CSC populations.

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