Cell lines of the same anatomic site and histologic type show large variability in intrinsic radiosensitivity and relative biological effectiveness to protons and carbon ions

2021 ◽  
Author(s):  
David B. Flint ◽  
Scott J. Bright ◽  
Conor H. McFadden ◽  
Teruaki Konishi ◽  
Daisuke Ohsawa ◽  
...  
Keyword(s):  
Cell Lines ◽  
Relative Biological Effectiveness ◽  
Histologic Type ◽  
Carbon Ions ◽  
Anatomic Site ◽  
Large Variability ◽  
Intrinsic Radiosensitivity ◽  
Biological Effectiveness

scholarly journals Cell lines of the same anatomic site and histologic type show large variability in radiosensitivity and relative biological effectiveness to protons and carbon ions

2020 ◽  
Author(s):  
David B. Flint ◽  
Scott J. Bright ◽  
Conor H. McFadden ◽  
Teruaki Konishi ◽  
Daisuke Ohsawa ◽  
...  
Keyword(s):  
Dna Repair ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Histologic Type ◽  
Anatomic Site ◽  
Repair Capacity ◽  
Dna Repair Capacity ◽  
Biological Effectiveness

AbstractPurposeTo show that radiation response across cancer cell lines of the same anatomic site and histologic type varies remarkably for protons and carbon (C) ions.Materials and MethodsWe measured and obtained from the literature clonogenic survival of human cancer cell lines of the lung (n=18), brain (n=10) and pancreas (n=10) exposed to photons, protons, and C-ions to assess their variability in response. We also treated cancer cell lines with DNA repair inhibitors prior to irradiation to assess how DNA repair capacity affects their variability in response. We quantified the variability in response by calculating the relative range (range/mean) and the coefficient of variation (COV) of the dose at 10% survival fraction (D10%) and relative biological effectiveness (RBE10%).ResultsThe relative range of D10% for lung cancer cell lines varied from 55-92% for photons, protons, and C-ions, with the relative range in RBE varying from 16-45% for protons and C-ions. For brain and pancreatic cancer cell lines, the relative range of D10% varied from 95-112%, and 39-75%, respectively, with the relative range in RBE varying from 27-33% and 25-50%, respectively. However, the COVs in D10% were approximately equal across radiation qualities, varying from 0.24±0.07–0.35±0.10, 0.35±0.09–0.69±0.62 and 0.13±0.03– 0.21±0.04 for lung, brain and pancreatic cancer cell lines, respectively. Greater relative ranges in D10% were observed in the cell lines with inhibited DNA repair, varying from 108%-157% for photons, protons, and C-ions, with relative ranges in RBE varying from 29-67%. The COVs in the D10% were also greater for the cell lines treated with inhibitors of DNA repair, varying from 0.34±0.09–0.41±0.06.ConclusionCell lines of the same anatomic site and histologic type have a remarkable variability in response, not only to photons but also to protons and C-ions. We attributed this variability to differences in DNA repair capacity.CategoryBiological Physics and Response Prediction

scholarly journals High LET Radiation Overcomes In Vitro Resistance to X-Rays of Chondrosarcoma Cell Lines

2019 ◽  
Vol 18 ◽  
pp. 153303381987130
Author(s):  
Francois Chevalier ◽  
Dounia Houria Hamdi ◽  
Charlotte Lepleux ◽  
Mihaela Temelie ◽  
Anaïs Nicol ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Lines ◽  
Relative Biological Effectiveness ◽  
Radiation Treatment ◽  
Malignant Tumors ◽  
Treatment Options ◽  
X Rays ◽  
Chondrosarcoma Cell ◽  
Biological Effectiveness

Chondrosarcomas are malignant tumors of the cartilage that are chemoresistant and radioresistant to X-rays. This restricts the treatment options essential to surgery. In this study, we investigated the sensitivity of chondrosarcoma to X-rays and C-ions in vitro. The sensitivity of 4 chondrosarcoma cell lines (SW1353, CH2879, OUMS27, and L835) was determined by clonogenic survival assays and cell cycle progression. In addition, biomarkers of DNA damage responses were analyzed in the SW1353 cell line. Chondrosarcoma cells showed a heterogeneous sensitivity toward irradiation. Chondrosarcoma cell lines were more sensitive to C-ions exposure compared to X-rays. Using D10 values, the relative biological effectiveness of C-ions was higher (relative biological effectiveness = 5.5) with cells resistant to X-rays (CH2879) and lower (relative biological effectiveness = 3.7) with sensitive cells (L835). C-ions induced more G2 phase blockage and micronuclei in SW1353 cells as compared to X-rays with the same doses. Persistent unrepaired DNA damage was also higher following C-ions irradiation. These results indicate that chondrosarcoma cell lines displayed a heterogeneous response to conventional radiation treatment; however, treatment with C-ions irradiation was more efficient in killing chondrosarcoma cells, compared to X-rays.

scholarly journals Investigating the impact of alpha/beta and LET d on relative biological effectiveness in scanned proton beams: An in vitro study based on human cell lines

2020 ◽  
Vol 47 (8) ◽  
pp. 3691-3702 ◽  
Author(s):  
Elisabeth Mara ◽  
Monika Clausen ◽  
Suphalak Khachonkham ◽  
Simon Deycmar ◽  
Clara Pessy ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Cell ◽  
Relative Biological Effectiveness ◽  
In Vitro Study ◽  
Vitro Study ◽  
Human Cell Lines ◽  
Biological Effectiveness ◽  
Alpha Beta ◽  
The Impact

scholarly journals Mapping the Relative Biological Effectiveness of Proton, Helium and Carbon Ions with High-Throughput Techniques

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3658
Author(s):  
Lawrence Bronk ◽  
Fada Guan ◽  
Darshana Patel ◽  
Duo Ma ◽  
Benjamin Kroger ◽  
...  
Keyword(s):  
High Throughput ◽  
Relative Biological Effectiveness ◽  
Biological Effects ◽  
Ion Beam ◽  
Particle Beam ◽  
Clonogenic Survival ◽  
Carbon Ions ◽  
Charged Particle Beams ◽  
Biological Effectiveness ◽  
Therapy Center

Large amounts of high quality biophysical data are needed to improve current biological effects models but such data are lacking and difficult to obtain. The present study aimed to more efficiently measure the spatial distribution of relative biological effectiveness (RBE) of charged particle beams using a novel high-accuracy and high-throughput experimental platform. Clonogenic survival was selected as the biological endpoint for two lung cancer cell lines, H460 and H1437, irradiated with protons, carbon, and helium ions. Ion-specific multi-step microplate holders were fabricated such that each column of a 96-well microplate is spatially situated at a different location along a particle beam path. Dose, dose-averaged linear energy transfer (LETd), and dose-mean lineal energy (yd) were calculated using an experimentally validated Geant4-based Monte Carlo system. Cells were irradiated at the Heidelberg Ion Beam Therapy Center (HIT). The experimental results showed that the clonogenic survival curves of all tested ions were yd-dependent. Both helium and carbon ions achieved maximum RBEs within specific yd ranges before biological efficacy declined, indicating an overkill effect. For protons, no overkill was observed, but RBE increased distal to the Bragg peak. Measured RBE profiles strongly depend on the physical characteristics such as yd and are ion specific.

scholarly journals An empirical model to predict survival curve and relative biological effectiveness after helium and carbon ion irradiation based solely on the cell survival after photon irradiation

2020 ◽  
Author(s):  
David B. Flint ◽  
Scott J. Bright ◽  
Conor H. McFadden ◽  
Teruaki Konishi ◽  
Daisuke Ohsawa ◽  
...  
Keyword(s):  
Cell Survival ◽  
Cell Lines ◽  
Empirical Model ◽  
Linear Correlation ◽  
Relative Biological Effectiveness ◽  
Ion Irradiation ◽  
Survival Curve ◽  
Carbon Ion ◽  
Wide Range ◽  
Biological Effectiveness

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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