scholarly journals Does the combination of hyperthermia with low LET (linear energy transfer) radiation induce anti-tumor effects equivalent to those seen with high LET radiation alone?

2021 ◽  
Vol 38 (1) ◽  
pp. 105-110
Author(s):  
Pernille B. Elming ◽  
Brita S. Sørensen ◽  
Harald Spejlborg ◽  
Jens Overgaard ◽  
Michael R. Horsman
2002 ◽  
Vol 80 (7) ◽  
pp. 644-649 ◽  
Author(s):  
D Coelho ◽  
B Fischer ◽  
V Holl ◽  
P Dufour ◽  
J M Denis ◽  
...  

The involvement of the tumor suppressor p53 gene in the sensitivity of many cell types towards low linear energy transfer (LET) radiation is now well established. However, little information is available on the relationship between p53 status of tumor cells and their ability to undergo apoptosis following exposure to high-LET radiation. Here we present the results of experiments carried out with the human lymphoblastoid cell line TK6 and its p53 knock-out counterpart NH32. Cells were irradiated at doses ranging from 0.25 to 8 Gy with fast neutrons (65 MeV), carbon ions (95 MeV/nucleon), and X rays (15 MV). For both cell lines, the occurrence of apoptosis, determined by the quantification of hypodiploid particles as well as the activation of several caspases, was compared with their sensitivity towards high-LET radiation. Results indicate that p53 is involved in the response of TK6 cells to fast neutrons and carbon ions, as measured by cell proliferation and occurrence of apoptosis. However, p53-deficient cells are still able to undergo apoptosis following irradiation. This suggests that heavy ions and fast neutrons induce cellular damage that is not under the control of p53. The involvement of executioner caspases in high-LET radiation induced apoptosis was also evaluated by use of specific inhibitors.Key words: fast neutrons, carbon ions, apoptosis, p53, lymphoblastoid cell line.


2014 ◽  
Vol 289 (44) ◽  
pp. 30635-30644 ◽  
Author(s):  
Hongyan Wang ◽  
Xiang Wang ◽  
Guangnan Chen ◽  
Xiangming Zhang ◽  
Xiaobing Tang ◽  
...  

High linear energy transfer (LET) radiation from space heavy charged particles or a heavier ion radiotherapy machine kills more cells than low LET radiation, mainly because high LET radiation-induced DNA damage is more difficult to repair. Relative biological effectiveness (RBE) is the ratio of the effects generated by high LET radiation to low LET radiation. Previously, our group and others demonstrated that the cell-killing RBE is involved in the interference of high LET radiation with non-homologous end joining but not homologous recombination repair. This effect is attributable, in part, to the small DNA fragments (≤40 bp) directly produced by high LET radiation, the size of which prevents Ku protein from efficiently binding to the two ends of one fragment at the same time, thereby reducing non-homologous end joining efficiency. Here we demonstrate that Ape1, an enzyme required for processing apurinic/apyrimidinic (known as abasic) sites, is also involved in the generation of small DNA fragments during the repair of high LET radiation-induced base damage, which contributes to the higher RBE of high LET radiation-induced cell killing. This discovery opens a new direction to develop approaches for either protecting astronauts from exposure to space radiation or benefiting cancer patients by sensitizing tumor cells to high LET radiotherapy.


Author(s):  
Jeremy Pearson ◽  
George Miller ◽  
Mikael Nilsson

Treatment of used nuclear fuel through solvent extraction separation processes is hindered by radiolytic damage from radioactive isotopes present in used fuel. The nature of the damage caused by the radiation may depend on the radiation type, whether it be low linear energy transfer (LET) such as gamma radiation or high LET such as alpha radiation. Used nuclear fuel contains beta/gamma emitting isotopes but also a significant amount of transuranics which are generally alpha emitters. Studying the respective effects on matter of both of these types of radiation will allow for accurate prediction and modeling of process performance losses with respect to dose. Current studies show that alpha radiation has milder effects than that of gamma. This is important to know because it will mean that solvent extraction solutions exposed to alpha radiation may last longer than expected and need less repair and replacement. These models are important for creating robust, predictable, and economical processes that have strong potential for mainstream adoption on the commercial level. The effects of gamma radiation on solvent extraction ligands have been more extensively studied than the effects of alpha radiation. This is due to the inherent difficulty in producing a sufficient and confluent dose of alpha particles within a sample without leaving the sample contaminated with long lived radioactive isotopes. Helium ion beam and radioactive isotope sources have been studied in the literature. We have developed a method for studying the effects of high LET radiation in situ via 10B activation and the high LET particles that result from the 10B(n,α)7Li reaction which follows. Our model for dose involves solving a partial differential equation representing absorption by 10B of an isentropic field of neutrons penetrating a sample. This method has been applied to organic solutions of TBP and CMPO, two ligands common in TRU solvent extraction treatment processes. Rates of degradation of TBP and CMPO and their respective degradation products in the presence of high LET radiation are presented and discussed. These results are also compared to gamma studies performed in our lab and other gamma and alpha studies found in the literature. The possible application of this method to a variety of other solvent extraction ligands to study the effects of high LET radiation is also considered.


2016 ◽  
Vol 57 (6) ◽  
pp. 596-606 ◽  
Author(s):  
Koichi Ando ◽  
Dudley T. Goodhead

Abstract Carbon-ion radiotherapy has been used to treat more than 9000 cancer patients in the world since 1994. Spreading of the Bragg peak is necessary for carbon-ion radiotherapy, and is designed based on the linear–quadratic model that is commonly used for photon therapy. Our recent analysis using in vitro cell kills and in vivo mouse tissue reaction indicates that radiation quality affects mainly the alpha terms, but much less the beta terms, which raises the question of whether this is true in other biological systems. Survival parameters alpha and beta for 45 in vitro mammalian cell lines were obtained by colony formation after irradiation with carbon ions, fast neutrons and X-rays. Relationships between survival parameters and linear energy transfer (LET) below 100 keV/μm were obtained for 4 mammalian cell lines. Mouse skin reaction and tumor growth delay were measured after fractionated irradiation. The Fe-plot provided survival parameters of the tissue reactions. A clear separation between X-rays and high-LET radiation was observed for alpha values, but not for beta values. Alpha values/terms increased with increasing LET in any cells and tissues studied, while beta did not show a systematic change. We have found a puzzle or contradiction in common interpretations of the linear-quadratic model that causes us to question whether the model is appropriate for interpreting biological effectiveness of high-LET radiation up to 500 keV/μm, probably because of inconsistency in the concept of damage interaction. A repair saturation model proposed here was good enough to fit cell kill efficiency by radiation of wide-ranged LET. A model incorporating damage complexity and repair saturation would be suitable for heavy-ion radiotherapy.


2014 ◽  
Vol 25 (S1) ◽  
pp. 75-79
Author(s):  
Mariangela Cestelli Guidi ◽  
Chiara Mirri ◽  
Emiliano Fratini ◽  
Valerio Licursi ◽  
Augusto Marcelli

2007 ◽  
Vol 254 (1) ◽  
pp. 54-62 ◽  
Author(s):  
Sami Benzina ◽  
Frederic Debomy ◽  
Jean-Pierre Bergerat ◽  
Jean-Marc Denis ◽  
John Gueulette ◽  
...  

2020 ◽  
Vol 98 (8) ◽  
pp. 427-433
Author(s):  
Ahmed Alanazi ◽  
Jintana Meesungnoen ◽  
Jean-Paul Jay-Gerin

FLASH radiotherapy is a new irradiation method in which large doses of ionizing radiation are delivered to tumors almost instantly (a few milliseconds), paradoxically sparing healthy tissue while preserving anti-tumor activity. Although this technique is primarily studied in the context of electron and photon therapies, proton delivery at high dose rates can also reduce the adverse side effects on normal cells. So far, no definitive mechanism has been proposed to explain the differences in the responses to radiation between tumor and normal tissues. Given that living cells and tissues consist mainly of water, we set out to study the effects of high dose rates on the radiolysis of water by protons in the energy range of 150 keV – 500 MeV (i.e., for linear energy transfer (LET) values between ∼72.2 and 0.23 keV/μm, respectively) using Monte Carlo simulations. To validate our methodology, however, we, first, report here the results of our calculations of the yields (G values) of the radiolytically produced species, namely the hydrated electron ([Formula: see text]), •OH, H•, H2, and H2O2, for low dose rates. Overall, our simulations agree very well with the experiment. In the presence of oxygen, [Formula: see text] and H• atoms are rapidly converted into superoxide anion or hydroperoxyl radicals, with a well-defined maximum of [Formula: see text] at ∼1 μs. This maximum decreases substantially when going from low-LET 500 MeV to high-LET 150 keV irradiating protons. Differences in the geometry of the proton track structure with increasing LET readily explain this diminution in [Formula: see text] radicals.


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