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Cited by 56Effects of Radiation ExposureDNA Repair MechanismsSpaceflight effects on biology

DNA Damage Baseline Predicts Resilience to Space Radiation and Radiotherapy

Open access
Pariset, Eloise, Bertucci, Antonella, Petay, Margaux, Malkani, Sherina, Lopez Macha, Alejandra, Paulino Lima, Ivan G., Gomez Gonzalez, Vanesa, Tin, Antony S. +5 more·2020·Cell Reports
DOI 10.1016/j.celrep.2020.108434PMC PMC7784531
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Abstract

Deep space exploration will require real-time, minimally invasive monitoring of astronaut health to mitigate the potential health impairments caused by space radiation and microgravity. Genotoxic stress in humans can be monitored by quantifying the amount of DNA double-strand breaks (DSBs) in immune cells from a simple finger prick. In a cohort of 674 healthy donors, we show that the endogenous level of DSBs increases with age and with latent cytomegalovirus infection. To map the range of human responses to space radiation, we then study DSB induction and repair in immune cells from 319 healthy donors after the cells are exposed to galactic cosmic ray components and lymphocytes from 30 cancer patients after radiotherapy. Individuals with low baseline DSB have fewer clinical complications, enhanced DNA damage repair responses, and a functional dose-dependent cytokine response in healthy donor cells. This supports the use of DSB monitoring for health resilience in space.

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References 66 · Cited by 56

Research works printed but not linked: 53

  1. Åhsberg J, Tsapogas P, Qian H, Zetterblad J, Zandi S, MÅnsson R, Jönsson J-I, and Sigvardsson M (2010). Interleukin-7-induced Stat-5 acts in synergy with Flt-3 signaling to stimulate expansion of hematopoietic progenitor cells. J. Biol. Chem 285, 36275– 36284. 20829349 PMC2978555
  2. An Y, Jiang W, Andraos TY, Reddy JP, Yehia ZA, Lloyd S, Duvic M, D’Souza NM, Milgrom SA, Pinnix CC, (2019). Multi-institutional Investigation: Circulating CD4:CD8 ratio is a prognosticator of response to total skin electron beam radiation in mycosis fungoides. Radiother. Oncol 131, 88– 92. 30773193 PMC6662194
  3. Azzam EI, Jay-Gerin J-P, and Pain D (2012). Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury. Cancer Lett 327, 48– 60. 22182453 PMC3980444
  4. Basch E, Reeve BB, Mitchell SA, Clauser SB, Minasian LM, Dueck AC, Mendoza TR, Hay J, Atkinson TM, Abernethy AP, (2014). Development of the National Cancer Institute’s patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE). J. Natl. Cancer Inst 106, dju244. 25265940 PMC4200059
  5. Braun LH, Baumann D, Zwirner K, Eipper E, Hauth F, Peter A, Zips D, and Gani C (2019). Neutrophil-to-Lymphocyte Ratio in Rectal Cancer-Novel Biomarker of Tumor Immunogenicity During Radiotherapy or Confounding Variable? Int. J. Mol. Sci 20, 2448. PMC6566677 31108935
  6. Cadet J, Delatour T, Douki T, Gasparutto D, Pouget J-P, Ravanat J-L, and Sauvaigo S (1999). Hydroxyl radicals and DNA base damage. Mutat. Res 424, 9– 21. 10064846
  7. Citrin DE, and Mitchell JB (2017). Mechanisms of normal tissue injury from irradiation. Semin. Radiat. Oncol 27, 316– 324. 28865514 PMC5653270
  8. Collin F (2019). Chemical basis of reactive oxygen species reactivity and involvement in neurodegenerative diseases. Int. J. Mol. Sci 20, 2407. PMC6566277 31096608
  9. Costes SV, Boissière A, Ravani S, Romano R, Parvin B, and Barcellos-Hoff MH (2006). Imaging features that discriminate between foci induced by high- and low-LET radiation in human fibroblasts. Radiat. Res 165, 505– 515. 16669704
  10. Costes SV, Ponomarev A, Chen JL, Nguyen D, Cucinotta FA, and Barcellos-Hoff MH (2007). Image-based modeling reveals dynamic redistribution of DNA damage into nuclear sub-domains. PLoS Comput. Biol 3, e155. 17676951 PMC1937017
  11. Costes SV, Chiolo I, Pluth JM, Barcellos-Hoff MH, and Jakob B (2010). Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization. Mutat. Res 704, 78– 87. 20060491 PMC3951968
  12. Crucian BE, Stowe RP, Pierson DL, and Sams CF (2008). Immune system dysregulation following short- vs long-duration spaceflight. Aviat. Space Environ. Med 79, 835– 843. 18785351
  13. Crucian B, Stowe RP, Mehta S, Quiriarte H, Pierson D, and Sams C (2015). Alterations in adaptive immunity persist during long-duration spaceflight. NPJ Microgravity 1, 15013. 28725716 PMC5515498
  14. Cucinotta FA, Wang H, and Huff JL (2009). Risk of acute or late central nervous system effects from radiation exposure In Human health and performance risks of space exploration missions, McPhee J and Charles J, eds. (NASA), pp. 191– 212.
  15. Di Marzo N, Chisci E, and Giovannoni R (2018). The role of hydrogen peroxide in redox-dependent signaling: Homeostatic and pathological responses in mammalian cells. Cells 7, 156. PMC6211135 30287799
  16. Doan PL, Himburg HA, Helms K, Russell JL, Fixsen E, Quarmyne M, Harris JR, Deoliviera D, Sullivan JM, Chao NJ, (2013). Epidermal growth factor regulates hematopoietic regeneration after radiation injury. Nat. Med 19, 295– 304. 23377280 PMC3594347
  17. Fernandez-Gonzalo R, Baatout S, and Moreels M (2017). Impact of particle irradiation on the immune system: from the clinic to mars. Front. Immunol 8, 177. 28275377 PMC5319970
  18. Ferrara N (2002). VEGF and the quest for tumour angiogenesis factors. Nat. Rev. Cancer 2, 795– 803. 12360282
  19. Frasca D, Barattini P, Tirindelli D, Guidi L, Bartoloni C, Errani A, Costanzo M, Tricerri A, Pierelli L, and Doria G (1999). Effect of age on DNA binding of the ku protein in irradiated human peripheral blood mononuclear cells (PBMC). Exp. Gerontol 34, 645– 658. 10530790
  20. Garm C, Moreno-Villanueva M, Bürkle A, Petersen I, Bohr VA, Christensen K, and Stevnsner T (2013). Age and gender effects on DNA strand break repair in peripheral blood mononuclear cells. Aging Cell 12, 58– 66. 23088435 PMC4586247
  21. Georgescu W, Osseiran A, Rojec M, Liu Y, Bombrun M, Tang J, and Costes SV (2015). Characterizing the DNA Damage Response by Cell Tracking Algorithms and Cell Features Classification Using High-Content Time-Lapse Analysis. PLoS ONE 10, e0129438. 26107175 PMC4479605
  22. Hoppe RT, Medeiros LJ, Warnke RA, and Wood GS (1995). CD8-positive tumor-infiltrating lymphocytes influence the long-term survival of patients with mycosis fungoides. J. Am. Acad. Dermatol 32, 448– 453. 7868714
  23. Itkin T, Ludin A, Gradus B, Gur-Cohen S, Kalinkovich A, Schajnovitz A, Ovadya Y, Kollet O, Canaani J, Shezen E, (2012). FGF-2 expands murine hematopoietic stem and progenitor cells via proliferation of stromal cells, c-Kit activation, and CXCL12 down-regulation. Blood 120, 1843– 1855. 22645180
  24. Johnson WE, Li C, and Rabinovic A (2007). Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics 8, 118– 127. 16632515
  25. Krukowski K, Jones T, Campbell-Beachler M, Nelson G, and Rosi S (2018). Peripheral T cells as a biomarker for oxygen-ion-radiation-induced social impairments. Radiat. Res 190, 186– 193. 29809107
  26. Kumar S, Suman S, Fornace AJ Jr., and Datta K (2018). Space radiation triggers persistent stress response, increases senescent signaling, and decreases cell migration in mouse intestine. Proc. Natl. Acad. Sci. USA 115, E9832– E9841. 30275302 PMC6196540
  27. Lee Y, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, Beckett M, Sharma R, Chin R, Tu T, (2009). Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood 114, 589– 595. 19349616 PMC2713472
  28. Leek JT, Johnson WE, Parker HS, Jaffe AE, and Storey JD (2012). The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics 28, 882– 883. 22257669 PMC3307112
  29. Li L, Xia Y, Nguyen A, Lai YH, Feng L, Mosmann TR, and Lo D (1999). Effects of Th2 cytokines on chemokine expression in the lung: IL-13 potently induces eotaxin expression by airway epithelial cells. J. Immunol 162, 2477– 2487. 10072486
  30. Løhr M, Jensen A, Eriksen L, Grønbæk M, Loft S, and Møller P (2015). Association between age and repair of oxidatively damaged DNA in human peripheral blood mononuclear cells. Mutagenesis 30, 695– 700. 25925070
  31. Maciejewski B, Withers HR, Taylor JM, and Hliniak A (1990). Dose fractionation and regeneration in radiotherapy for cancer of the oral cavity and oropharynx. Part 2. Normal tissue responses: acute and late effects. Int. J. Radiat. Oncol. Biol. Phys 18, 101– 111. 2298613
  32. Mara E, Clausen M, Khachonkham S, Deycmar S, Pessy C, Dörr W, Kuess P, Georg D, and Gruber S (2020). Investigating the impact of alpha/beta and LETd on relative biological effectiveness in scanned proton beams: An in vitro study based on human cell lines. Med. Phys 47, 3691– 3702. 32347564 PMC7496287
  33. Maxwell CA, Fleisch MC, Costes SV, Erickson AC, Boissière A, Gupta R, Ravani SA, Parvin B, and Barcellos-Hoff MH (2008). Targeted and nontargeted effects of ionizing radiation that impact genomic instability. Cancer Res 68, 8304– 8311. 18922902
  34. Nelson GA (2016). Space Radiation and Human Exposures, A Primer. Radiat. Res 185, 349– 358. 27018778
  35. Neumaier T, Swenson J, Pham C, Polyzos A, Lo AT, Yang P, Dyball J, Asaithamby A, Chen DJ, Bissell MJ, (2012). Evidence for formation of DNA repair centers and dose-response nonlinearity in human cells. Proc. Natl. Acad. Sci. USA 109, 443– 448. 22184222 PMC3258602
  36. Nosel I, Vaurijoux A, Barquinero JF, and Gruel G (2013). Characterization of gene expression profiles at low and very low doses of ionizing radiation. DNA Repair (Amst.) 12, 508– 517. 23683873
  37. Ochola DO, Sharif R, Bedford JS, Keefe TJ, Kato TA, Fallgren CM, Demant P, Costes SV, and Weil MM (2019). Persistence of Gamma-H2AX Foci in Bronchial Cells Correlates with Susceptibility to Radiation Associated Lung Cancer in Mice. Radiat. Res 191, 67– 75. 30398394
  38. Ozsahin M, Crompton NE, Gourgou S, Kramar A, Li L, Shi Y, Sozzi WJ, Zouhair A, Mirimanoff RO, and Azria D (2005). CD4 and CD8 T-lymphocyte apoptosis can predict radiation-induced late toxicity: a prospective study in 399 patients. Clin. Cancer Res 11, 7426– 7433. 16243816
  39. Pariset E, Penninckx S, Kerbaul CD, Guiet E, Macha AL, Cekanaviciute E, Snijders AM, Mao J-H, Paris F, and Costes SV (2020). 53BP1 Repair Kinetics for Prediction of In Vivo Radiation Susceptibility in 15 Mouse Strains. Radiat. Res Published online September 29, 2020 10.1667/RADE-20-00122.1. 32991727 · DOI
  40. Paul F, Pellegrini S, and Uzé G (2015). IFNA2: The prototypic human alpha interferon. Gene 567, 132– 137. 25982860 PMC5629289
  41. Paul AM, Mhatre SD, Cekanaviciute E, Schreurs A-S, Tahimic CG, Globus RK, Crucian B, and Bhattacharya S (2020). Neutrophil to lymphocyte ratio: A prognostic indicator for astronaut health. Front. Immunol 11, 564950. 33224136 PMC7667275
  42. Paul-Gilloteaux P, Potiron V, Delpon G, Supiot S, Chiavassa S, Paris F, and Costes SV (2017). Optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes. Sci. Rep 7, 2280. 28536438 PMC5442104
  43. Plante I, and Cucinotta FA (2011). Monte-Carlo simulation of ionizing radiation tracks. Application of Monte Carlo methods in biology, medicine and other fields of science In Applications of Monte Carlo Methods in Biology, Medicine and Other Fields of Science, Mode CJ, ed. (InTech), pp. 315– 356.
  44. Rogakou EP, Pilch DR, Orr AH, Ivanova VS, and Bonner WM (1998). DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J. Biol. Chem 273, 5858– 5868. 9488723
  45. Roos WP, Thomas AD, and Kaina B (2016). DNA damage and the balance between survival and death in cancer biology. Nat. Rev. Cancer 16, 20– 33. 26678314
  46. Saber CN, Grønhøj Larsen C, Dalianis T, and von Buchwald C (2016). Immune cells and prognosis in HPV-associated oropharyngeal squamous cell carcinomas: Review of the literature. Oral Oncol 58, 8– 13. 27311396
  47. Santana Carrero RM, Beceren-Braun F, Rivas SC, Hegde SM, Gangadharan A, Plote D, Pham G, Anthony SM, and Schluns KS (2019). IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses. Proc. Natl. Acad. Sci. USA 116, 599– 608. 30587590 PMC6329954
  48. Slater JD, Rossi CJ Jr., Yonemoto LT, Bush DA, Jabola BR, Levy RP, Grove RI, Preston W, and Slater JM (2004). Proton therapy for prostate cancer: the initial Loma Linda University experience. Int. J. Radiat. Oncol. Biol. Phys 59, 348– 352. 15145147
  49. Smith AO, Bowers SL, Stratman AN, and Davis GE (2013). Hematopoietic stem cell cytokines and fibroblast growth factor-2 stimulate human endothelial cell-pericyte tube co-assembly in 3D fibrin matrices under serum-free defined conditions. PLoS ONE 8, e85147. 24391990 PMC3877341
  50. Tang L, Hu HD, Hu P, Lan YH, Peng ML, Chen M, and Ren H (2007). Gene therapy with CX3CL1/Fractalkine induces antitumor immunity to regress effectively mouse hepatocellular carcinoma. Gene Ther 14, 1226– 1234. 17597794
  51. Turesson I, and Notter G (1984). The influence of fraction size in radiotherapy on the late normal tissue reaction—I: Comparison of the effects of daily and once-a-week fractionation on human skin. Int. J. Radiat. Oncol. Biol. Phys 10, 593– 598. 6735750
  52. Wagner M, Poeck H, Jahrsdoerfer B, Rothenfusser S, Prell D, Bohle B, Tuma E, Giese T, Ellwart JW, Endres S, and Hartmann G (2004). IL-12p70-dependent Th1 induction by human B cells requires combined activation with CD40 ligand and CpG DNA. J. Immunol 172, 954– 963. 14707068
  53. Zhang T, Yu H, Ni C, Zhang T, Liu L, Lv Q, Zhang Z, Wang Z, Wu D, Wu P, (2017). Hypofractionated stereotactic radiation therapy activates the peripheral immune response in operable stage I non-small-cell lung cancer. Sci. Rep 7, 4866. 28687760 PMC5501824

Authors
Pariset, E., Bertucci, A., Petay, M., Malkani, S., Lopez Macha, A., Paulino Lima, I. G., Gomez Gonzalez, V., Tin, A. S., Tang, J., Plante, I., Cekanaviciute, E., Vazquez, M., & Costes, S. V.
Affiliations
  • Ames Research Center (US)
  • Loma Linda University (US)
  • Epigen Biosciences (United States) (US)
  • National Aeronautics and Space Administration (US)
Corresponding author
Costes, Sylvain V.
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2020-12
Volume
33
Issue
10
Pages
108434
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2020.108434
PMC
PMC7784531
OpenAlex
W3107412089
Cited by
56
References
66
Citations by year
2026: 6 · 2025: 16 · 2024: 11 · 2023: 4 · 2022: 7 · 2021: 10 · 2020: 2
FWCI
2.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion, cc-by)
  • PubMed Central (acceptedVersion, cc-by)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
Funders
  • Lawrence Berkeley National Laboratory
  • National Institute of Allergy and Infectious Diseases
  • National Aeronautics and Space Administration
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Health Sciences › Medicine › Physiology › Spaceflight effects on biology
Keywords
DNA double-strand breaks, space radiation, radiotherapy, DNA repair, immune cells, galactic cosmic rays, cytomegalovirus infection, aging, astronaut health monitoring, microgravity, cytokine response, genotoxic stress, cancer patients
MeSH terms
Adult, Aged, DNA, DNA Damage, DNA Repair, Dose-Response Relationship, Radiation, Female, Histones, Humans, Male, Middle Aged, Prognosis, Radiation Tolerance, Space Flight, Weightlessness, Oxidative Stress, DNA Breaks, Double-Stranded

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