Monoenergetic 290 MeV/n carbon-ion beam biological lethal dose distribution surrounding the Bragg peak

Buglewicz, Dylan J.; Banks, Austin B.; Hirakawa, Hirokazu; Fujimori, A.; Kato, Takamitsu A.

doi:10.1038/s41598-019-42600-4

Cited by 12 publications

(26 citation statements)

References 31 publications

(29 reference statements)

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“…Irradiation was carried out as previously described ( 28 ) ( Figure 1 ). Prior to irradiation, cell culture flasks or SlideFlasks were placed upright with the capped end opposite to the proton beam source.…”

Section: Methodsmentioning

confidence: 99%

“…The files were cropped to exclude ridges of the T-25 flasks and narrowing neck of the bottle. These images were entered into an executable script created previously ( 28 ) via the MATLAB software (MATHWORKS, Natick, MA). The script allows .JPG files to be analyzed by pixel shade to create three-dimensional surface plots that can be adjusted to create virtual cell survival plots.…”

Section: Methodsmentioning

confidence: 99%

“…In order to clarify the true nature of the proton RBE from biological responses at the Bragg peak and the surrounding area, a position dependent analysis was carried out with 0.5 mm to a few millimeter increments to cover the proton beam paths ( 24 – 27 ). We utilized a horizontal irradiation system, which we previously developed ( 28 ). This irradiation system can visually show cellular cytotoxic locations in the flasks.…”

Section: Introductionmentioning

confidence: 99%

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High LET-Like Radiation Tracks at the Distal Side of Accelerated Proton Bragg Peak

et al. 2021

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Proton therapy is a type of hadron radiotherapy used for treating solid tumors. Unlike heavy charged elements, proton radiation is considered to be low LET (Linear Energy Transfer) radiation, like X-rays. However, the clinical SOBP (Spread Out Bragg Peak) proton radiation is considered to be higher in relative biological effectiveness (RBE) than both X-ray and their own entrance region. The RBE is estimated to be 1.1–1.2, which can be attributed to the higher LET at the SOBP region than at the entrance region. In order to clarify the nature of higher LET near the Bragg peak of proton radiation and its potential cytotoxic effects, we utilized a horizontal irradiation system with CHO cells. Additionally, we examined DNA repair mutants, analyzed cytotoxicity with colony formation, and assessed DNA damage and its repair with γ-H2AX foci assay in a high-resolution microscopic scale analysis along with the Bragg peak. Besides confirming that the most cytotoxic effects occurred at the Bragg peak, extended cytotoxicity was observed a few millimeters after the Bragg peak. γ-H2AX foci numbers reached a maximum at the Bragg peak and reduced dramatically after the Bragg peak. However, in the post-Bragg peak region, particle track-like structures were sporadically observed. This region contains foci that are more difficult to repair. The peak and post-Bragg peak regions contain rare high LET-like radiation tracks and can cause cellular lethality. This may have caused unwanted side effects and complexities of outputs for the proton therapy treatment.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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High LET-Like Radiation Tracks at the Distal Side of Accelerated Proton Bragg Peak

et al. 2021

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“…The cultures were fixed with absolute ethanol and stained with 0.1% crystal violet. Lastly, colonies containing more than 50 cells were scored as survivors [ 32 , 33 ].…”

Section: Methodsmentioning

confidence: 99%

Cytotoxicity and Mutagenicity of Narrowband UVB to Mammalian Cells

Buglewicz

Mussallem

Haskins

et al. 2020

Genes

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Phototherapy using narrowband ultraviolet-B (NB-UVB) has been shown to be more effective than conventional broadband UVB (BB-UVB) in treating a variety of skin diseases. To assess the difference in carcinogenic potential between NB-UVB and BB-UVB, we investigated the cytotoxicity via colony formation assay, genotoxicity via sister chromatid exchange (SCE) assay, mutagenicity via hypoxanthine phosphoribosyltransferase (HPRT) mutation assay, as well as cyclobutane pyrimidine dimer (CPD) formation and reactive oxygen species (ROS) generation in Chinese hamster ovary (CHO) and their NER mutant cells. The radiation dose required to reduce survival to 10% (D10 value) demonstrated BB-UVB was 10 times more cytotoxic than NB-UVB, and revealed that NB-UVB also induces DNA damage repaired by nucleotide excision repair. We also found that BB-UVB more efficiently induced SCEs and HPRT mutations per absorbed energy dosage (J/m2) than NB-UVB. However, SCE and HPRT mutation frequencies were observed to rise in noncytotoxic dosages of NB-UVB exposure. BB-UVB and NB-UVB both produced a significant increase in CPD formation and ROS formation (p < 0.05); however, higher dosages were required for NB-UVB. These results suggest that NB-UVB is less cytotoxic and genotoxic than BB-UVB, but can still produce genotoxic effects even at noncytotoxic doses.

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“…This safety profile probably reflects the fact that high LET ions behave similarly to low LET X-rays and protons while traveling through (normal) tissue at high speed, gaining their high LET properties only when slowing and stopping at the end of their tracks (in tumors) [63,92] . Thus, carbon ion LET and RBE are relatively low in the entrance region and increase dramatically in the Bragg peak, and the most damaging effects are confined to the tumor volume [63,93,94] .…”

Section: Radiobiological Properties Of Therapeutic Ionizing Radiationmentioning

confidence: 99%

Exploiting DNA repair pathways for tumor sensitization, mitigation of resistance, and normal tissue protection in radiotherapy

Nickoloff¹,

Taylor²,

Sharma³

et al. 2021

CDR

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More than half of cancer patients are treated with radiotherapy, which kills tumor cells by directly and indirectly inducing DNA damage, including cytotoxic DNA double-strand breaks (DSBs). Tumor cells respond to these threats by activating a complex signaling network termed the DNA damage response (DDR). The DDR arrests the cell cycle, upregulates DNA repair, and triggers apoptosis when damage is excessive. The DDR signaling and DNA repair pathways are fertile terrain for therapeutic intervention. This review highlights strategies to improve therapeutic gain by targeting DDR and DNA repair pathways to radiosensitize tumor cells, overcome intrinsic and acquired tumor radioresistance, and protect normal tissue. Many biological and environmental factors determine tumor and normal cell responses to ionizing radiation and genotoxic chemotherapeutics. These include cell type and cell cycle phase distribution; tissue/tumor microenvironment and oxygen levels; DNA damage load and quality; DNA repair capacity; and susceptibility to apoptosis or other active or passive cell death pathways. We provide an overview of radiobiological parameters associated with X-ray, proton, and carbon ion radiotherapy; DNA repair and DNA damage signaling pathways; and other factors that regulate tumor and normal cell responses to radiation. We then focus on recent studies exploiting DSB repair pathways to enhance radiotherapy therapeutic gain.

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Monoenergetic 290 MeV/n carbon-ion beam biological lethal dose distribution surrounding the Bragg peak

Cited by 12 publications

References 31 publications

High LET-Like Radiation Tracks at the Distal Side of Accelerated Proton Bragg Peak

High LET-Like Radiation Tracks at the Distal Side of Accelerated Proton Bragg Peak

Cytotoxicity and Mutagenicity of Narrowband UVB to Mammalian Cells

Exploiting DNA repair pathways for tumor sensitization, mitigation of resistance, and normal tissue protection in radiotherapy

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