Influence of track directions on the biological consequences in cells irradiated with high LET heavy ions

Fujii, Yukihiko; Yurkon, Charles R.; Maeda, Jun; Genet, Stefan C.; Okayasu, Ryuichi; Kitamura, Hisashi; Fujimori, A.; Kato, Takamitsu A.

doi:10.3109/09553002.2013.767990

Cited by 5 publications

(4 citation statements)

References 63 publications

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“…Moreover, as the LET of the particles increases, there is an increase in the frequency and complexity of complex DSBs produced. The complexity of DNA damage was analyzed with two parameters of foci distribution including the cluster of multiple foci at one location and foci track structure, both of which are signatures of high LET radiation exposure ( 29 , 30 ). The kinetics of foci disappearance after high LET radiation exposure is known to be slower than that after low LET radiation.…”

Section: Discussionmentioning

confidence: 99%

Biological Effects of Monoenergetic Carbon Ions and Their Associated Secondary Particles

Buglewicz¹,

Walsh²,

Hirakawa³

et al. 2022

Front. Oncol.

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DNA double-strand breaks (DSBs) are the main factor behind carbon-ion radiation therapy (CIRT)-induced cell death. Nuclear interactions along the beam path between the primary carbon ions and targets result in nuclear fragmentation of carbon ions and recoiled particles. These secondary particles travel further distances past the Bragg peak to the tail region, leading to unwanted biological effects that may result in cytotoxicity in critical organs and secondary induced tumors following CIRT. Here, we confirmed that the density of the DSB distributions increases as the cell survival decreases at the Bragg peak and demonstrated that by visualizing DSBs, the various LET fragmentation ions and recoiled particles produced differences in their biological effects in the post-Bragg peak tail regions. This suggests that the density of the DSBs within the high-LET track structures, rather than only their presence, is important for inducing cell death. These results are essential for CIRT treatment planning to limit the amount of healthy cell damage and reducing both the late effect and the secondary tumor-associated risk.

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Section: Discussionmentioning

confidence: 99%

Biological Effects of Monoenergetic Carbon Ions and Their Associated Secondary Particles

Buglewicz¹,

Walsh²,

Hirakawa³

et al. 2022

Front. Oncol.

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“…In addition to the quantitative results, a qualitative observation was that many 64 Cu-ATSM-incubated cells, both CHO wild type and xrs5, had what appeared to be large and intense foci, along with many regular foci. These are thought to be clustered γH2AX foci [ 31 ], potentially resulting from an Auger cascade. In CHO wild-type cells with 0.8 Bq/cell uptake, ∼10 foci were produced and ∼80% of cells were dead (see Figs 2 A and 1 C).…”

Section: Discussionmentioning

confidence: 99%

Validation of⁶⁴Cu-ATSM damaging DNA via high-LET Auger electron emission

et al. 2015

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Radioactive copper (II) (diacetyl-bis N4-methylthiosemicarbazone) (Cu-ATSM) isotopes were originally developed for the imaging of hypoxia in tumors. Because the decay of a 64Cu atom is emitting not only positrons but also Auger electrons, this radionuclide has great potential as a theranostic agent. However, the success of 64Cu-ATSM internal radiation therapy would depend on the contribution of Auger electrons to tumor cell killing. Therefore, we designed a cell culture system to define the contributions to cell death from Auger electrons to support or refute our hypothesis that the majority of cell death from 64Cu-ATSM is a result of high-LET Auger electrons and not positrons or other low-LET radiation. Chinese hamster ovary (CHO) wild type and DNA repair–deficient xrs5 cells were exposed to 64Cu-ATSM during hypoxic conditions. Surviving fractions were compared with those surviving gamma-radiation, low-LET hadron radiation, and high-LET heavy ion exposure. The ratio of the D10 values (doses required to achieve 10% cell survival) between CHO wild type and xrs5 cells suggested that 64Cu-ATSM toxicity is similar to that of high-LET Carbon ion radiation (70 keV/μm). γH2AX foci assays confirmed DNA double-strand breaks and cluster damage by high-LET Auger electrons from 64Cu decay, and complex types of chromosomal aberrations typical of high-LET radiation were observed after 64Cu-ATSM exposure. The majority of cell death was caused by high-LET radiation. This work provides strong evidence that 64Cu-ATSM damages DNA via high-LET Auger electrons, supporting further study and consideration of 64Cu-ATSM as a cancer treatment modality for hypoxic tumors.

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“…RBE of proton and photon is about 1-1.1 (48). According to the different doses and the observed biological effect endpoints, the RBE of carbon ions is generally between 1.5 and 4.5 (49). HIRT can place the tumor in the Bragg peak with high dose and high biological effect.…”

Section: Research Frontiers and Challengesmentioning

confidence: 99%

Visualized Analysis of Heavy Ion Radiotherapy: Development, Barriers and Future Directions

Jin

Zhang

et al. 2021

Front. Oncol.

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BackgroundHeavy ion radiotherapy (HIRT) has great advantages as tumor radiotherapy.MethodsBased on 1,558 literatures from core collections of Web of Science from 1980 to 2020, this study visually analyzes the evolution of HIRT research, and sorts out the hotspots and trends of HIRT research using CiteSpace software.ResultsResearch on HIRT has received more extensive attention over the last 40 years. The development of HIRT is not only closely related to radiation and oncology, but also closely related to the development of human society. In terms of citation frequency, “International Journal of Radiation Oncology*Biology*Physics” was the top journal. In terms of influence, “Radiotherapy and Oncology” was the top journal. “Radiation therapy” and “carbon ion radiotherapy” were the two most frequently used keywords in this field.ConclusionThe evolution of the HIRT research has occurred in approximately three stages, including technological exploration, safety and effectiveness research and technological breakthroughs. Finally, some suggestions for future research are put forward.

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Influence of track directions on the biological consequences in cells irradiated with high LET heavy ions

Abstract: Therefore, we concluded that high fluence per dose is more effective than low fluence per dose to produce radiation-induced chromosomal aberrations and to kill exposed cells following high LET heavy-ion exposure.

Cited by 5 publications

References 63 publications

Biological Effects of Monoenergetic Carbon Ions and Their Associated Secondary Particles

Biological Effects of Monoenergetic Carbon Ions and Their Associated Secondary Particles

Validation of⁶⁴Cu-ATSM damaging DNA via high-LET Auger electron emission

Visualized Analysis of Heavy Ion Radiotherapy: Development, Barriers and Future Directions

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Influence of track directions on the biological consequences in cells irradiated with high LET heavy ions

Abstract: Therefore, we concluded that high fluence per dose is more effective than low fluence per dose to produce radiation-induced chromosomal aberrations and to kill exposed cells following high LET heavy-ion exposure.

Cited by 5 publications

References 63 publications

Biological Effects of Monoenergetic Carbon Ions and Their Associated Secondary Particles

Biological Effects of Monoenergetic Carbon Ions and Their Associated Secondary Particles

Validation of64Cu-ATSM damaging DNA via high-LET Auger electron emission

Visualized Analysis of Heavy Ion Radiotherapy: Development, Barriers and Future Directions

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Validation of⁶⁴Cu-ATSM damaging DNA via high-LET Auger electron emission