Evaluation of Histone Deacetylase Inhibitors as Radiosensitizers for Proton and Light Ion Radiotherapy

Johnson, Alicia M.; Bennett, Paula V.; Sanidad, Katherine Z.; Hoang, Anthony; Jardine, James H.; Keszenman, Deborah J.; Wilson, Paul F.

doi:10.3389/fonc.2021.735940

Title: Evaluation of Histone Deacetylase Inhibitors as Radiosensitizers for Proton and Light Ion Radiotherapy

Journal Article · Thu Aug 26 00:00:00 EDT 2021 · Frontiers in Oncology

DOI:https://doi.org/10.3389/fonc.2021.735940· OSTI ID:1842813

Johnson, Alicia M. ^[1]; Bennett, Paula V. ^[1]; Sanidad, Katherine Z. ^[1]; Hoang, Anthony ^[1]; Jardine, James H. ^[1]; Keszenman, Deborah J. ^[2]; Wilson, Paul F. ^[3]

Brookhaven National Lab. (BNL), Upton, NY (United States)
Brookhaven National Lab. (BNL), Upton, NY (United States); Univ. de la Republica (UdelaR), Salto (Uruguay). Centro Universitario Regional Litorl Norte, Lab. de Radiobiologia Medica y Ambiental
Brookhaven National Lab. (BNL), Upton, NY (United States); Univ. of California Davis, Sacramento, CA (United States)

Significant opportunities remain for pharmacologically enhancing the clinical effectiveness of proton and carbon ion-based radiotherapies to achieve both tumor cell radiosensitization and normal tissue radioprotection. We investigated whether pretreatment with the hydroxamate-based histone deacetylase inhibitors (HDACi) SAHA (vorinostat), M344, and PTACH impacts radiation-induced DNA double-strand break (DSB) induction and repair, cell killing, and transformation (acquisition of anchorage-independent growth in soft agar) in human normal and tumor cell lines following gamma ray and light ion irradiation. Treatment of normal NFF28 primary fibroblasts and U2OS osteosarcoma, A549 lung carcinoma, and U87MG glioma cells with 5–10 µM HDACi concentrations 18 h prior to cesium-137 gamma irradiation resulted in radiosensitization measured by clonogenic survival assays and increased levels of colocalized gamma-H2AX/53BP1 foci induction. We similarly tested these HDACi following irradiation with 200 MeV protons, 290 MeV/n carbon ions, and 350 MeV/n oxygen ions delivered in the Bragg plateau region. Unlike uniform gamma ray radiosensitization, effects of HDACi pretreatment were unexpectedly cell type and ion species-dependent with C-12 and O-16 ion irradiations showing enhanced G0/G1-phase fibroblast survival (radioprotection) and in some cases reduced or absent tumor cell radiosensitization. DSB-associated foci levels were similar for proton-irradiated DMSO control and SAHA-treated fibroblast cultures, while lower levels of induced foci were observed in SAHA-pretreated C-12 ion-irradiated fibroblasts. Fibroblast transformation frequencies measured for all radiation types were generally LET-dependent and lowest following proton irradiation; however, both gamma and proton exposures showed hyperlinear transformation induction at low doses (≤25 cGy). HDACi pretreatments led to overall lower transformation frequencies at low doses for all radiation types except O-16 ions but generally led to higher transformation frequencies at higher doses (>50 cGy). The results of these in vitro studies cast doubt on the clinical efficacy of using HDACi as radiosensitizers for light ion-based hadron radiotherapy given the mixed results on their radiosensitization effectiveness and related possibility of increased second cancer induction.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Brookhaven National Lab. (BNL), Upton, NY (United States)

Sponsoring Organization:: National Aeronautics and Space Administration (NASA); USDOE Laboratory Directed Research and Development (LDRD) Program

Grant/Contract Number:: SC0012704; AC02-98CH10886

OSTI ID:: 1842813

Report Number(s):: BNL-222689-2022-JAAM

Journal Information:: Frontiers in Oncology, Vol. 11; ISSN 2234-943X

Publisher:: Frontiers Research FoundationCopyright Statement

Country of Publication:: United States

Language:: English

References (69)

Kinetics and dose-response of residual 53BP1/γ-H2AX foci: Co-localization, relationship with DSB repair and clonogenic survival Marková, E.; Schultz, N.; Belyaev, I. Y. International Journal of Radiation Biology, Vol. 83, Issue 5 https://doi.org/10.1080/09553000601170469	journal	January 2007
Phase I Study of an Oral Histone Deacetylase Inhibitor, Suberoylanilide Hydroxamic Acid, in Patients With Advanced Cancer Kelly, William Kevin; O'Connor, Owen A.; Krug, Lee M. Journal of Clinical Oncology, Vol. 23, Issue 17 https://doi.org/10.1200/JCO.2005.14.167	journal	June 2005
Phase I and Pharmacokinetic Study of Vorinostat, A Histone Deacetylase Inhibitor, in Combination with Carboplatin and Paclitaxel for Advanced Solid Malignancies Ramalingam, Suresh S.; Parise, Robert A.; Ramananthan, Ramesh K. Clinical Cancer Research, Vol. 13, Issue 12 https://doi.org/10.1158/1078-0432.CCR-07-0162	journal	May 2007
Inhibition of homologous recombination with vorinostat synergistically enhances ganciclovir cytotoxicity Ladd, Brendon; Ackroyd, Jeffrey J.; Hicks, J. Kevin DNA Repair, Vol. 12, Issue 12 https://doi.org/10.1016/j.dnarep.2013.10.008	journal	December 2013
Structural Basis for the Methylation State-Specific Recognition of Histone H4-K20 by 53BP1 and Crb2 in DNA Repair Botuyan, Maria Victoria; Lee, Joseph; Ward, Irene M. Cell, Vol. 127, Issue 7 https://doi.org/10.1016/j.cell.2006.10.043	journal	December 2006
53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark Fradet-Turcotte, Amélie; Canny, Marella D.; Escribano-Díaz, Cristina Nature, Vol. 499, Issue 7456 https://doi.org/10.1038/nature12318	journal	June 2013
Differential Radiosensitivity Phenotypes of DNA-PKcs Mutations Affecting NHEJ and HRR Systems following Irradiation with Gamma-Rays or Very Low Fluences of Alpha Particles Lin, Yu-Fen; Nagasawa, Hatsumi; Little, John B. PLoS ONE, Vol. 9, Issue 4 https://doi.org/10.1371/journal.pone.0093579	journal	April 2014
Karyotypes of Human Lymphocytes Exposed to High-Energy Iron Ions Durante, M.; George, K.; Wu, H. Radiation Research, Vol. 158, Issue 5 https://doi.org/10.1667/0033-7587(2002)158[0581:KOHLET]2.0.CO;2	journal	November 2002
Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation Sutherland, B. M.; Bennett, P. V.; Sidorkina, O. Proceedings of the National Academy of Sciences, Vol. 97, Issue 1 https://doi.org/10.1073/pnas.97.1.103	journal	January 2000
Relative Biological Effectiveness Variation Along Monoenergetic and Modulated Bragg Peaks of a 62-MeV Therapeutic Proton Beam: A Preclinical Assessment Chaudhary, Pankaj; Marshall, Thomas I.; Perozziello, Francesca M. International Journal of Radiation OncologyBiologyPhysics, Vol. 90, Issue 1 https://doi.org/10.1016/j.ijrobp.2014.05.010	journal	September 2014
Split-dose exposures versus dual ion exposure in human cell neoplastic transformation Bennett, Paula V.; Cutter, Noelle C.; Sutherland, Betsy M. Radiation and Environmental Biophysics, Vol. 46, Issue 2 https://doi.org/10.1007/s00411-006-0091-y	journal	January 2007
Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes Garcia-Manero, Guillermo; Yang, Hui; Bueso-Ramos, Carlos Blood, Vol. 111, Issue 3 https://doi.org/10.1182/blood-2007-06-098061	journal	February 2008
Histone deacetylase (HDAC) inhibitor activation of p21WAF1 involves changes in promoter-associated proteins, including HDAC1 Gui, C. -Y.; Ngo, L.; Xu, W. S. Proceedings of the National Academy of Sciences, Vol. 101, Issue 5 https://doi.org/10.1073/pnas.0307708100	journal	January 2004
The CGL1 (HeLa × Normal Skin Fibroblast) Human Hybrid Cell Line: A History of Ionizing Radiation Induced Effects on Neoplastic Transformation and Novel Future Directions in SNOLAB Pirkkanen, Jake S.; Boreham, Douglas R.; Mendonca, Marc S. Radiation Research, Vol. 188, Issue 4.2 https://doi.org/10.1667/RR14911.1	journal	October 2017
Role of Homologous Recombination in the Alpha-Particle-Induced Bystander Effect for Sister Chromatid Exchanges and Chromosomal Aberrations Nagasawa, H.; Peng, Y.; Wilson, P. F. Radiation Research, Vol. 164, Issue 2 https://doi.org/10.1667/RR3420	journal	August 2005
Issues for Simulation of Galactic Cosmic Ray Exposures for Radiobiological Research at Ground-Based Accelerators Kim, Myung-Hee Y.; Rusek, Adam; Cucinotta, Francis A. Frontiers in Oncology, Vol. 5 https://doi.org/10.3389/fonc.2015.00122	journal	June 2015
High LET-Like Radiation Tracks at the Distal Side of Accelerated Proton Bragg Peak Horendeck, Dakota; Walsh, Kade D.; Hirakawa, Hirokazu Frontiers in Oncology, Vol. 11 https://doi.org/10.3389/fonc.2021.690042	journal	June 2021
Carbon Ion Therapy: A Modern Review of an Emerging Technology Malouff, Timothy D.; Mahajan, Anita; Krishnan, Sunil Frontiers in Oncology, Vol. 10 https://doi.org/10.3389/fonc.2020.00082	journal	February 2020
Hallmarks of Cancer: The Next Generation Hanahan, Douglas; Weinberg, Robert A. Cell, Vol. 144, Issue 5 https://doi.org/10.1016/j.cell.2011.02.013	journal	March 2011
FDA Approval Summary: Vorinostat for Treatment of Advanced Primary Cutaneous T-Cell Lymphoma Mann, B. S.; Johnson, J. R.; Cohen, M. H. The Oncologist, Vol. 12, Issue 10 https://doi.org/10.1634/theoncologist.12-10-1247	journal	October 2007
Mapping the Relative Biological Effectiveness of Proton, Helium and Carbon Ions with High-Throughput Techniques Bronk, Lawrence; Guan, Fada; Patel, Darshana Cancers, Vol. 12, Issue 12 https://doi.org/10.3390/cancers12123658	journal	December 2020
Differential Repair Protein Recruitment at Sites of Clustered and Isolated DNA Double-Strand Breaks Produced by High-Energy Heavy Ions Jakob, Burkhard; Dubiak-Szepietowska, Monika; Janiel, Ellen Scientific Reports, Vol. 10, Issue 1 https://doi.org/10.1038/s41598-020-58084-6	journal	January 2020
Efficient Rejoining of DNA Double-Strand Breaks despite Increased Cell-Killing Effectiveness following Spread-Out Bragg Peak Carbon-Ion Irradiation Averbeck, Nicole B.; Topsch, Jana; Scholz, Michael Frontiers in Oncology, Vol. 6 https://doi.org/10.3389/fonc.2016.00028	journal	February 2016
DNA Double-stranded Breaks Induce Histone H2AX Phosphorylation on Serine 139 Rogakou, Emmy P.; Pilch, Duane R.; Orr, Ann H. Journal of Biological Chemistry, Vol. 273, Issue 10, p. 5858-5868 https://doi.org/10.1074/jbc.273.10.5858	journal	March 1998
Valproic Acid Sensitizes Hepatocellular Carcinoma Cells to Proton Therapy by Suppressing NRF2 Activation Yu, Jeong Il; Choi, Changhoon; Shin, Sung-Won Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/s41598-017-15165-3	journal	November 2017
Induction of Anchorage-Independent Growth in Primary Human Cells Exposed to Protons or HZE Ions Separately or in Dual Exposures Sutherland, B. M.; Cuomo, N. C.; Bennett, P. V. Radiation Research, Vol. 164, Issue 4 https://doi.org/10.1667/rr3357.1	journal	October 2005
Homologous Recombination Contributes to the Repair of DNA Double-Strand Breaks Induced by High-Energy Iron Ions Zafar, Faria; Seidler, Sara B.; Kronenberg, Amy Radiation Research, Vol. 173, Issue 1 https://doi.org/10.1667/RR1910.1	journal	January 2010
Complex exchanges are responsible for the increased effectiveness of C-ions compared to X-rays at the first post-irradiation mitosis Lee, Ryonfa; Sommer, Sylwester; Hartel, Carola Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Vol. 701, Issue 1 https://doi.org/10.1016/j.mrgentox.2010.03.004	journal	August 2010
Repair Kinetics of DNA Double Strand Breaks Induced by Simulated Space Radiation Oizumi, Takashi; Ohno, Rieko; Yamabe, Souichiro Life, Vol. 10, Issue 12 https://doi.org/10.3390/life10120341	journal	December 2020
Histone Deacetylase Inhibitor Induced Radiation Sensitization Effects on Human Cancer Cells after Photon and Hadron Radiation Exposure Gerelchuluun, Ariungerel; Maeda, Junko; Manabe, Eri International Journal of Molecular Sciences, Vol. 19, Issue 2 https://doi.org/10.3390/ijms19020496	journal	February 2018
Recognition, signaling, and repair of DNA double-strand breaks produced by ionizing radiation in mammalian cells: The molecular choreography Thompson, Larry H. Mutation Research/Reviews in Mutation Research, Vol. 751, Issue 2 https://doi.org/10.1016/j.mrrev.2012.06.002	journal	October 2012
Strategies to Enhance Radiosensitivity to Heavy Ion Radiation Therapy Lee, Younghyun; Okayasu, Ryuichi International Journal of Particle Therapy, Vol. 5, Issue 1 https://doi.org/10.14338/IJPT-18-00014.1	journal	August 2018
Carbon Ion Radiotherapy: A Review of Clinical Experiences and Preclinical Research, with an Emphasis on DNA Damage/Repair Mohamad, Osama; Sishc, Brock; Saha, Janapriya Cancers, Vol. 9, Issue 12 https://doi.org/10.3390/cancers9060066	journal	June 2017
Human cell transformation in the study of sunlight-induced cancers in the skin of man Sutherland, Betsy M.; Freeman, Abbie G.; Bennett, Paula V. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 199, Issue 2 https://doi.org/10.1016/0027-5107(88)90219-9	journal	June 1988
Second cancer risk after primary cancer treatment with three‐dimensional conformal, intensity‐modulated, or proton beam radiation therapy Xiang, Michael; Chang, Daniel T.; Pollom, Erqi L. Cancer, Vol. 126, Issue 15 https://doi.org/10.1002/cncr.32938	journal	May 2020
A defect in DNA double strand break processing in cells from unaffected parents of retinoblastoma patients and other apparently normal humans Kato, Takamitsu A.; Wilson, Paul F.; Nagasawa, Hatsumi DNA Repair, Vol. 6, Issue 6 https://doi.org/10.1016/j.dnarep.2007.01.008	journal	June 2007
Proton-HZE-Particle Sequential Dual-Beam Exposures Increase Anchorage-Independent Growth Frequencies in Primary Human Fibroblasts Zhou, Guangming; Bennett, Paula V.; Cutter, Noelle C. Radiation Research, Vol. 166, Issue 3 https://doi.org/10.1667/RR0596.1	journal	September 2006
Development of vorinostat: Current applications and future perspectives for cancer therapy Richon, Victoria M.; Garcia-Vargas, Jose; Hardwick, James S. Cancer Letters, Vol. 280, Issue 2 https://doi.org/10.1016/j.canlet.2009.01.002	journal	August 2009
Vorinostat, a histone deacetylase inhibitor, enhances the response of human tumor cells to ionizing radiation through prolongation of γ-H2AX foci Munshi, Anupama; Tanaka, Toshimitsu; Hobbs, Marvette L. Molecular Cancer Therapeutics, Vol. 5, Issue 8 https://doi.org/10.1158/1535-7163.MCT-06-0022	journal	August 2006
Enhancement of Radiation Sensitivity of Human Squamous Carcinoma Cells by Histone Deacetylase Inhibitors Zhang, Yin; Jung, Manfred; Dritschilo, Anatoly Radiation Research, Vol. 161, Issue 6 https://doi.org/10.1667/rr3192	journal	June 2004
Modulation of radiation response by histone deacetylase inhibition Chinnaiyan, Prakash; Vallabhaneni, Geetha; Armstrong, Eric International Journal of Radiation OncologyBiologyPhysics, Vol. 62, Issue 1 https://doi.org/10.1016/j.ijrobp.2004.12.088	journal	May 2005
Histone deacetylase inhibitor induces DNA damage, which normal but not transformed cells can repair Lee, J. - H.; Choy, M. L.; Ngo, L. Proceedings of the National Academy of Sciences, Vol. 107, Issue 33 https://doi.org/10.1073/pnas.1008522107	journal	August 2010
Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization Costes, S. V.; Chiolo, I.; Pluth, J. M. Mutation Research/Reviews in Mutation Research, Vol. 704, Issue 1-3, p. 78-87 https://doi.org/10.1016/j.mrrev.2009.12.006	journal	April 2010
Response of Primary Human Fibroblasts Exposed to Solar Particle Event Protons Stisova, Viktorie; Abele, William H.; Thompson, Keith H. Radiation Research, Vol. 176, Issue 2 https://doi.org/10.1667/rr2490.1	journal	August 2011
Biological Effectiveness of Accelerated Protons for Chromosome Exchanges George, Kerry A.; Hada, Megumi; Cucinotta, Francis A. Frontiers in Oncology, Vol. 5 https://doi.org/10.3389/fonc.2015.00226	journal	October 2015
Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites Yasuda, Takeshi; Kagawa, Wataru; Ogi, Tomoo PLOS Genetics, Vol. 14, Issue 3 https://doi.org/10.1371/journal.pgen.1007277	journal	March 2018
Histone deacetylase inhibitors as radiosensitisers: effects on DNA damage signalling and repair Groselj, B.; Sharma, N. L.; Hamdy, F. C. British Journal of Cancer, Vol. 108, Issue 4 https://doi.org/10.1038/bjc.2013.21	journal	January 2013
Endogenous DNA damage clusters in human skin, 3-D model, and cultured skin cells Bennett, Paula V.; Cuomo, Noelle L.; Paul, Sunirmal Free Radical Biology and Medicine, Vol. 39, Issue 6 https://doi.org/10.1016/j.freeradbiomed.2005.05.008	journal	September 2005
Comparative Risk Predictions of Second Cancers After Carbon-Ion Therapy Versus Proton Therapy Eley, John G.; Friedrich, Thomas; Homann, Kenneth L. International Journal of Radiation OncologyBiologyPhysics, Vol. 95, Issue 1 https://doi.org/10.1016/j.ijrobp.2016.02.032	journal	May 2016
Radiation Sensitivity of Primary Fibroblasts from Hereditary Retinoblastoma Family Members and Some Apparently Normal Controls: Colony Formation Ability during Continuous Low-Dose-Rate Gamma Irradiation Wilson, Paul F.; Nagasawa, Hatsumi; Warner, Christy L. Radiation Research, Vol. 169, Issue 5 https://doi.org/10.1667/RR1333.1	journal	May 2008
ATM and DNA-PK Function Redundantly to Phosphorylate H2AX after Exposure to Ionizing Radiation Stiff, Tom; O’Driscoll, Mark; Rief, Nicole Cancer Research, Vol. 64, Issue 7 https://doi.org/10.1158/0008-5472.CAN-03-3207	journal	April 2004
Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks Huyen, Yentram; Zgheib, Omar; DiTullio Jr, Richard A. Nature, Vol. 432, Issue 7015 https://doi.org/10.1038/nature03114	journal	November 2004
P53 Binding Protein 1 (53bp1) Is an Early Participant in the Cellular Response to DNA Double-Strand Breaks Schultz, Linda B.; Chehab, Nabil H.; Malikzay, Asra The Journal of Cell Biology, Vol. 151, Issue 7 https://doi.org/10.1083/jcb.151.7.1381	journal	December 2000
Physical basis of radiation protection in space travel Durante, Marco; Cucinotta, Francis A. Reviews of Modern Physics, Vol. 83, Issue 4 https://doi.org/10.1103/RevModPhys.83.1245	journal	November 2011
Biological Characterization of Low-Energy Ions with High-Energy Deposition on Human Cells Saha, Janapriya; Wilson, Paul; Thieberger, Peter Radiation Research, Vol. 182, Issue 3 https://doi.org/10.1667/RR13747.1	journal	August 2014
Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi Suraweera, Amila; O’Byrne, Kenneth J.; Richard, Derek J. Frontiers in Oncology, Vol. 8 https://doi.org/10.3389/fonc.2018.00092	journal	March 2018
Enhancement of Radiation Response in Osteosarcoma and Rhabomyosarcoma Cell Lines by Histone Deacetylase Inhibition Blattmann, Claudia; Oertel, Susanne; Ehemann, Volker International Journal of Radiation OncologyBiologyPhysics, Vol. 78, Issue 1 https://doi.org/10.1016/j.ijrobp.2010.03.010	journal	September 2010
Radiosensitization of glioblastoma cells using a histone deacetylase inhibitor (SAHA) comparing carbon ions with X-rays Barazzuol, Lara; Jeynes, J. Charles G.; Merchant, Michael J. International Journal of Radiation Biology, Vol. 91, Issue 1 https://doi.org/10.3109/09553002.2014.946111	journal	June 2014
Modulation of cellular radiation responses by histone deacetylase inhibitors Karagiannis, T. C.; El-Osta, A. Oncogene, Vol. 25, Issue 28 https://doi.org/10.1038/sj.onc.1209417	journal	February 2006
Impact of Charged Particle Exposure on Homologous DNA Double-Strand Break Repair in Human Blood-Derived Cells Rall, Melanie; Kraft, Daniela; Volcic, Meta Frontiers in Oncology, Vol. 5 https://doi.org/10.3389/fonc.2015.00250	journal	November 2015
RNF168 ubiquitylates 53BP1 and controls its response to DNA double-strand breaks Bohgaki, M.; Bohgaki, T.; El Ghamrasni, S. Proceedings of the National Academy of Sciences, Vol. 110, Issue 52 https://doi.org/10.1073/pnas.1320302111	journal	December 2013
Advantages and Limitations in the Use of Combination Therapies with Charged Particle Radiation Therapy Tsuboi, Koji International Journal of Particle Therapy, Vol. 5, Issue 1 https://doi.org/10.14338/IJPT-18-00019.1	journal	August 2018
Tumor Microenvironment as a Regulator of Radiation Therapy: New Insights into Stromal-Mediated Radioresistance Krisnawan, Varintra E.; Stanley, Jennifer A.; Schwarz, Julie K. Cancers, Vol. 12, Issue 10 https://doi.org/10.3390/cancers12102916	journal	October 2020
Inter-individual variation in DNA double-strand break repair in human fibroblasts before and after exposure to low doses of ionizing radiation Wilson, Paul F.; Nham, Peter B.; Urbin, Salustra S. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 683, Issue 1-2, p. 91-97 https://doi.org/10.1016/j.mrfmmm.2009.10.013	journal	January 2010
In vitro characterization of cells derived from chordoma cell line U-CH1 following treatment with X-rays, heavy ions and chemotherapeutic drugs Kato, Takamitsu A.; Tsuda, Akihisa; Uesaka, Mitsuru Radiation Oncology, Vol. 6, Issue 1 https://doi.org/10.1186/1748-717X-6-116	journal	September 2011
Induction and Repair of DNA DSB as Revealed by H2AX Phosphorylation Foci in Human Fibroblasts Exposed to Low- and High-LET Radiation: Relationship with Early and Delayed Reproductive Cell Death Antonelli, F.; Campa, A.; Esposito, G. Radiation Research, Vol. 183, Issue 4 https://doi.org/10.1667/RR13855.1	journal	April 2015
Relative biological effectiveness (RBE), quality factor ( Q ), and radiation weighting factor ( w _R ): ICRP Publication 92: Approved by the Commission in January 2003 Valentin, J. Annals of the ICRP, Vol. 33, Issue 4 https://doi.org/10.1016/S0146-6453(03)00024-1	journal	October 2003
Combination of suberoylanilide hydroxamic acid with heavy ion therapy shows promising effects in infantile sarcoma cell lines Oertel, Susanne; Thiemann, Markus; Richter, Karsten Radiation Oncology, Vol. 6, Issue 1 https://doi.org/10.1186/1748-717X-6-119	journal	September 2011
Solar particle event storm shelter requirements for missions beyond low Earth orbit Townsend, L. W.; Adams, J. H.; Blattnig, S. R. Life Sciences in Space Research, Vol. 17 https://doi.org/10.1016/j.lssr.2018.02.002	journal	May 2018

Similar Records

Dose-Rate Effects of Protons and Light Ions for DNA Damage Induction, Survival and Transformation in Apparently Normal Primary Human Fibroblasts

Journal Article · Wed Dec 15 00:00:00 EST 2021 · Radiation Research · OSTI ID:1842813

Bennett, Paula V.; Johnson, Alicia M.; Ackerman, Sarah E.; +3 more

Comparison of the biological effectiveness of 45 MeV C-ions and {gamma}-rays in inducing early and late effects in normal human primary fibroblasts

Journal Article · Thu Jul 18 00:00:00 EDT 2013 · AIP Conference Proceedings · OSTI ID:1842813

Fratini, E.; Balduzzi, M.; Antonelli, F.; +9 more

ATM-Dependent Hyper-Radiosensitivity in Mammalian Cells Irradiated by Heavy Ions

Journal Article · Tue Sep 01 00:00:00 EDT 2009 · International Journal of Radiation Oncology, Biology and Physics · OSTI ID:1842813

Lian, Xue; Furusawa, Yoshiya; Jianping, Cao; +2 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HDAC
inhibitor
SAHA
radiosensitization double-strand break
ionizing
radiation
protons
carbon

Title: Evaluation of Histone Deacetylase Inhibitors as Radiosensitizers for Proton and Light Ion Radiotherapy

Citation Formats

References (69)

Similar Records

Related Subjects