Radiosensitizing Effect of PARP Inhibition on Chondrosarcoma and Chondrocyte Cells Is Dependent on Radiation LET
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Cultures
2.2. Drug Treatments
2.3. Irradiation
2.4. Clonogenic Assay
2.5. MTT Toxicity Test
2.6. Sequencing
2.7. Western Blotting Analysis
2.8. Statistics
3. Results
3.1. Clonogenic Survival of Chondrosarcoma and Chondrocyte Cells Is Dependent on LET
3.2. Similar Low Toxicity and Effective Activity of PARP Inhibitor
3.3. Differential Mutation Status and Genomic Instability: GIScar Score
3.4. Radiosensitizing Effect of PARPi Depends on Radiation LET
3.5. Specific Activation of DNA Repair Pathways Depends on Radiation LET
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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D10 | RBE | ER | ||
---|---|---|---|---|
OUMS27 | X-ray | 6.17 | ||
X-ray + Olaparib | 5.18 | 1.19 * | ||
C-ions | 2.02 | 3.05 | ||
C-ions + Olaparib | 2.22 | 0.91 | ||
JJ012 | X-ray | 7.5 | ||
X-ray + Olaparib | 5.04 | 1.5 * | ||
C-ions | 2.24 | 3.37 | ||
C-ions + Olaparib | 2.22 | 1.01 | ||
MC615 | X-ray | 7.58 | ||
X-ray + Olaparib | 5.52 | 1.37 * | ||
C-ions | 2.36 | 3.21 | ||
C-ions + Olaparib | 2.27 | 1.04 |
Cell Line | Gene | Event | Mutation | GIScar Score | Number of Large Genomic Events * |
---|---|---|---|---|---|
JJ012 | IDH1 | missense substitution | p.Arg132Gly | ||
SLX4 | missense substitution | p.Thr345Asn | |||
TP53 | missense substitution | p.Gly199Val | 6 | ||
ARID1A | frameshift | p.Gln1552Hisfs*21 | 0.154 | ||
ARID1B | missense substitution | p.Pro1019Leu | |||
ARID1B | frameshift | p.Gly351Metfs*11 | |||
OUMS27 | TP53 | frameshift | p.Ser149Tyrfs*31 | 0.408 | 27 |
EMSY | intronic mutation | g.76260993C>A |
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Gilbert, A.; Tudor, M.; Delaunay, A.; Leman, R.; Levilly, J.; Atkinson, A.; Castéra, L.; Dinischiotu, A.; Savu, D.I.; Valable, S.; et al. Radiosensitizing Effect of PARP Inhibition on Chondrosarcoma and Chondrocyte Cells Is Dependent on Radiation LET. Biomolecules 2024, 14, 1071. https://doi.org/10.3390/biom14091071
Gilbert A, Tudor M, Delaunay A, Leman R, Levilly J, Atkinson A, Castéra L, Dinischiotu A, Savu DI, Valable S, et al. Radiosensitizing Effect of PARP Inhibition on Chondrosarcoma and Chondrocyte Cells Is Dependent on Radiation LET. Biomolecules. 2024; 14(9):1071. https://doi.org/10.3390/biom14091071
Chicago/Turabian StyleGilbert, Antoine, Mihaela Tudor, Amandine Delaunay, Raphaël Leman, Julien Levilly, Alexandre Atkinson, Laurent Castéra, Anca Dinischiotu, Diana Iulia Savu, Samuel Valable, and et al. 2024. "Radiosensitizing Effect of PARP Inhibition on Chondrosarcoma and Chondrocyte Cells Is Dependent on Radiation LET" Biomolecules 14, no. 9: 1071. https://doi.org/10.3390/biom14091071