Radical recombination and antioxidants: a hypothesis on the FLASH effect mechanism

References

• Adrian G, Konradsson E, Lempart M, Back S, Ceberg C, Petersson K. 2020. The FLASH effect depends on oxygen concentration. Brit J Radiol. 93(1106):20190702.
   PubMed Web of Science ®Google Scholar
• Alper T. 1983. Oxygen as radiosensitizer: methods of analysis. Int J Radiat Biol Relat Stud Phys Chem Med. 44(3):313–314.
   PubMed Web of Science ®Google Scholar
• Alper T. 1984. Adding two components of radiosensitization by oxygen. Int J Radiat Biol Relat Stud Phys Chem Med. 46(5):569–585.
   PubMed Web of Science ®Google Scholar
• Antunes F, Salvador A, Marinho HS, Alves R, Pinto RE. 1996. Lipid peroxidation in mitochondrial inner membranes. I. An integrative kinetic model. Free Radic Biol Med. 21(7):917–943.
   PubMed Web of Science ®Google Scholar
• Ayala A, Munoz MF, Arguelles S. 2014. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev. 2014:360438.
   PubMed Web of Science ®Google Scholar
• Babbs CF, Steiner MG. 1990. Simulation of free radical reactions in biology and medicine: a new two-compartment kinetic model of intracellular lipid peroxidation. Free Radic Biol Med. 8(5):471–485.
   PubMed Web of Science ®Google Scholar
• Berry RJ, Hall EJ, Forster DW, Storr TH, Goodman MJ. 1969. Survival of mammalian cells exposed to X rays at ultra-high dose-rates. Br J Radiol. 42(494):102–107.
   PubMed Web of Science ®Google Scholar
• Bourhis J, Sozzi WJ, Jorge PG, Gaide O, Bailat C, Duclos F, Patin D, Ozsahin M, Bochud F, Germond JF, et al. 2019. Treatment of a first patient with FLASH-radiotherapy. Radiother Oncol. 139:18–22.
   PubMed Web of Science ®Google Scholar
• Buonanno M, Grilj V, Brenner DJ. 2019. Biological effects in normal cells exposed to FLASH dose rate protons. Radiother Oncol. 139:51–55.
   PubMed Web of Science ®Google Scholar
• Cadet J, Davies KJA. 2017. Oxidative DNA damage and repair: an introduction. Free Radic Biol Med. 107:2–12.
   PubMed Web of Science ®Google Scholar
• Cao X, Zhang R, Esipova TV, Allu SR, Ashraf R, Rahman M, Gunn JR, Bruza P, Gladstone DJ, Williams BB, et al. 2021. Quantification of oxygen depletion during FLASH irradiation in vitro and in vivo. Int J Radiat Oncol Biol Phys. 111(1):240–248.
   PubMed Web of Science ®Google Scholar
• Cuddihy SL, Parker A, Harwood DT, Vissers MC, Winterbourn CC. 2008. Ascorbate interacts with reduced glutathione to scavenge phenoxyl radicals in HL60 cells. Free Radic Biol Med. 44(8):1637–1644.
   PubMed Web of Science ®Google Scholar
• Dizdaroglu M, Jaruga P. 2012. Mechanisms of free radical-induced damage to DNA. Free Radic Res. 46(4):382–419.
   PubMed Web of Science ®Google Scholar
• Favaudon V, Caplier L, Monceau V, Pouzoulet F, Sayarath M, Fouillade C, Poupon MF, Brito I, Hupe P, Bourhis J, et al. 2014. Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice. Sci Transl Med. 6(245):245ra93.
   PubMed Web of Science ®Google Scholar
• Favaudon V, Labarbe R, Limoli CL. 2021. Model studies of the role of oxygen in the FLASH effect. Med Phys. 49(3):2068–2081.
   Web of Science ®Google Scholar
• Fouillade C, Curras-Alonso S, Giuranno L, Quelennec E, Heinrich S, Bonnet-Boissinot S, Beddok A, Leboucher S, Karakurt HU, Bohec M, et al. 2020. FLASH irradiation spares lung progenitor cells and limits the incidence of radio-induced senescence. Clin Cancer Res. 26(6):1497–1506.
   PubMed Web of Science ®Google Scholar
• Gamcsik MP, Kasibhatla MS, Teeter SD, Colvin OM. 2012. Glutathione levels in human tumors. Biomarkers. 17(8):671–691.
   PubMed Web of Science ®Google Scholar
• Gebicki S, Gebicki JM. 1993. Formation of peroxides in amino-acids and proteins exposed to oxygen free-radicals. Biochemical Journal. 289(3):743–749.
   PubMedGoogle Scholar
• Guo R, Huang F, Zhang B, Yan Y, Che J, Jin Y, Zhuang Y, Dong R, Li Y, Tan B, et al. 2019. GSH activated biotin-tagged near-infrared probe for efficient cancer imaging. Theranostics. 9(12):3515–3525.
   PubMed Web of Science ®Google Scholar
• Hildenbrand K, Schulte-Frohlinde D. 1997. Time-resolved EPR studies on the reaction rates of peroxyl radicals of poly(acrylic acid) and of calf thymus DNA with glutathione. Re-examination of a rate constant for DNA. Int J Radiat Biol. 71(4):377–385.
   PubMed Web of Science ®Google Scholar
• Howard-Flanders P, Moore D. 1958. The time interval after pulsed irradiation within which injury to bacteria can be modified by dissolved oxygen: I. A search for an effect of oxygen 0.02 second after pulsed irradiation. Radiat Res. 9(4):422–437.
   PubMed Web of Science ®Google Scholar
• Jin JY, Gu A, Wang W, Oleinick NL, Machtay M, Spring Kong FM. 2020. Ultra-high dose rate effect on circulating immune cells: a potential mechanism for FLASH effect? Radiother Oncol. 149:55–62.
   PubMed Web of Science ®Google Scholar
• Kennedy L, Sandhu JK, Harper ME, Cuperlovic-Culf M. 2020. Role of glutathione in cancer: from mechanisms to therapies. Biomolecules. 10(10):1429.
   PubMed Web of Science ®Google Scholar
• Labarbe R, Hotoiu L, Barbier J, Favaudon V. 2020. A physicochemical model of reaction kinetics supports peroxyl radical recombination as the main determinant of the FLASH effect. Radiother Oncol. 153:303–310.
   PubMed Web of Science ®Google Scholar
• Li S, Zhang W, Xue H, Xing R, Yan X. 2020. Tumor microenvironment-oriented adaptive nanodrugs based on peptide self-assembly. Chem Sci. 11(33):8644–8656.
   PubMed Web of Science ®Google Scholar
• Ling CC, Michaels HB, Epp ER, Gerweck LE, Peterson EC. 1978. Oxygen diffusion into mammalian-cells following ultrahigh dose-rate irradiation and lifetime estimates of oxygen sensitive species. Radiat Res. 76(3):522–494.
   PubMed Web of Science ®Google Scholar
• Liu CC, Gebicki JM. 2012. Intracellular GSH and ascorbate inhibit radical-induced protein chain peroxidation in HL-60 cells. Free Radic Biol Med. 52(2):420–426.
   PubMed Web of Science ®Google Scholar
• McKeown SR. 2014. Defining normoxia, physoxia and hypoxia in tumours-implications for treatment response. BJR. 87(1035):20130676.
   Google Scholar
• Michaels HB, Epp ER, Ling CC, Peterson EC. 1978. Oxygen sensitization of CHO cells at ultrahigh dose rates: prelude to oxygen diffusion studies. Radiat Res. 76(3):510–521.
   PubMed Web of Science ®Google Scholar
• Michaels HB, Hunt JW. 1978. A model for radiation damage in cells by direct effect and by indirect effect: a radiation chemistry approach. Radiat Res. 74(1):23–34.
   PubMed Web of Science ®Google Scholar
• Millar BC, Fielden EM, Steele JJ. 1979. A biphasic radiation survival response of mammalian cells to molecular oxygen. Int J Radiat Biol Relat Stud Phys Chem Med. 36(2):177–180.
   PubMed Web of Science ®Google Scholar
• Montay-Gruel P, Acharyac MM, Peterssona K, Alikhanic L, Yakkala C, Allen BD Ollivier J, Petit B, Jorge PG Syage AR. 2019. Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species. Proc Natl Acad Sci USA. 116(22):8.
   Web of Science ®Google Scholar
• Montay-Gruel P, Petersson K, Jaccard M, Boivin G, Germond J-F, Petit B, Doenlen R, Favaudon V, Bochud F, Bailat C, et al. 2017. Irradiation in a flash: unique sparing of memory in mice after whole brain irradiation with dose rates above 100 Gy/s. Radiother Oncol. 124(3):365–369.
   PubMed Web of Science ®Google Scholar
• Nauser T, Gebicki JM. 2017a. Physiological concentrations of ascorbate cannot prevent the potentially damaging reactions of protein radicals in humans. Chem Res Toxicol. 30(9):1702–1710.
   PubMed Web of Science ®Google Scholar
• Nauser T, Gebicki JM. 2017b. Reaction rates of glutathione and ascorbate with alkyl radicals are too slow for protection against protein peroxidation in vivo. Arch Biochem Biophys. 633:118–123.
   PubMed Web of Science ®Google Scholar
• Nauser T, Koppenol WH, Schoneich C. 2015. Protein thiyl radical reactions and product formation: a kinetic simulation. Free Radic Biol Med. 80:158–163.
   PubMed Web of Science ®Google Scholar
• Neta P, Huie RE, Ross AB. 1990. Rate constants for reactions of peroxyl radicals in fluid solutions. J Phys Chem Ref Data. 19(2):413–513.
   Web of Science ®Google Scholar
• Neuzil J, Gebicki JM, Stocker R. 1993. Radical-induced chain oxidation of proteins and its inhibition by chain-breaking antioxidants. Biochem J. 293(3):601–606.
   PubMedGoogle Scholar
• Spiro IJ, Ling CC, Stickler R, Gaskill J. 1985. Oxygen radiosensitisation at low dose rate. Br J Radiol. 58(688):357–363.
   PubMed Web of Science ®Google Scholar
• Spitz DR, Buettner GR, Petronek MS, St-Aubin JJ, Flynn RT, Waldron TJ, Limoli CL. 2019. An integrated physico-chemical approach for explaining the differential impact of FLASH versus conventional dose rate irradiation on cancer and normal tissue responses. Radiother Oncol. 139:23–27.
   PubMed Web of Science ®Google Scholar
• Traverso N, Ricciarelli R, Nitti M, Marengo B, Furfaro AL, Pronzato MA, Marinari UM, Domenicotti C. 2013. Role of glutathione in cancer progression and chemoresistance. Oxid Med Cell Longev. 2013:972913.
   PubMed Web of Science ®Google Scholar
• Tudek B, Zdżalik-Bielecka D, Tudek A, Kosicki K, Fabisiewicz A, Speina E. 2017. Lipid peroxidation in face of DNA damage, DNA repair and other cellular processes. Free Radic Biol Med. 107:77–89.
   PubMed Web of Science ®Google Scholar
• Wardman P. 2020. Radiotherapy using high-intensity pulsed radiation beams (FLASH): a radiation-chemical perspective. Radiat Res. 194(6):607–617.
   PubMed Web of Science ®Google Scholar
• Wardman P. 2022. Approaches to modeling chemical reaction pathways in radiobiology. Int J Radiat Biol. 1–15. https://doi.org/10.1080/09553002.2022.2033342
   Google Scholar
• Wardman P, Von Sonntag C. 1995. Kinetic factors that control the fate of thiyl radicals in cells. Methods Enzymol. 251:31–45.
   PubMed Web of Science ®Google Scholar
• Weiss H, Epp ER, Heslin JM, Ling CC, Santomasso A. 1974. Oxygen depletion in cells irradiated at ultrahigh dose-rates and at conventional dose-rates. Int J Radiat Biol Relat Stud Phys Chem Med. 26(1):17–29.
   PubMed Web of Science ®Google Scholar