Modeling the biological response of normal human cells, including repair processes, to fractionated carbon beam irradiation

Wada, Mami; Suzuki, Masao; Liu, Cuihua; Kaneko, Y.; Fukuda, Satoshi; Andō, Kōichi; Matsufuji, Naruhiro

doi:10.1093/jrr/rrt012

Cited by 16 publications

(13 citation statements)

References 31 publications

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“…Large fraction sizes lead to a risk of osteoradionecrosis in C‐ion RT similar to that in RT. However, the conventional fraction size of C‐ion RT may not effectively decrease the risk of osteoradionecrosis compared to that of RT because the sublethal damage repair of normal tissue after C‐ion RT is smaller than that after RT …”

Section: Discussionmentioning

confidence: 99%

“…However, the conventional fraction size of C-ion RT may not effectively decrease the risk of osteoradionecrosis compared to that of RT because the sublethal damage repair of normal tissue after C-ion RT is smaller than that after RT. 21 ACC has been recognized as a radioresistant tumor. Mendenhall et al 22 reported on a series of 42 patients with head and neck ACC treated with RT alone, including brachytherapy, and the 5-year local control was 57%.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of the safety and efficacy of carbon ion radiotherapy for locally advanced adenoid cystic carcinoma of the tongue base

Koto¹,

Hasegawa²,

Takagi³

et al. 2016

Head & Neck

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluation of the safety and efficacy of carbon ion radiotherapy for locally advanced adenoid cystic carcinoma of the tongue base

Koto¹,

Hasegawa²,

Takagi³

et al. 2016

Head & Neck

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“…Fractionation of radiotherapy is thought to protect normal tissues by allowing repair of sublethal damage (3). In previous studies, sublethal damage repair was not detected in mammalian cells following fractionated high linear energy transfer (LET) irradiation such as carbon beam or thermal neutron irradiation (4,5). In this study, we investigated the effect of fractionated thermal and epithermal neutron beam irradiation on normal cells using a colony-formation assay to monitor cell survival rate and 53BP1 foci as markers of DNA damage.…”

mentioning

confidence: 99%

DNA Double-strand Breaks Induced byFractionated Neutron Beam Irradiation for Boron Neutron Capture Therapy

2017

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“…13) It is possible to use fractionated-dose irradiation, but this is less effective than a single dose because DNA repair (sublethal-damage repair) occurs during the inter-fraction intervals. 14,15) Due to these issues, there is great interest in the use of radiosensitizers, such as gold nanoparticles or heatshock-protein (Hsp) inhibitors, to improve the efficacy of cancer radiotherapy. 16,17) After irradiation of cells, early DNA repair responses, such as activation of ataxia telangiectasia mutated (ATM; a serine/ threonine protein kinase), formation of phosphorylated histone variant H2AX (γH2AX), and accumulation of tumor suppressor p53-binding protein 1 (53BP1), are induced within 1 h. 7,18) Activation of ATM induces phosphorylation of H2AX at DNA damage sites and triggers formation of a DNA damage response complex of RAD80, BRCA1 and 53BP1.…”

mentioning

confidence: 99%

Radiosensitizing Effect of TRPV1 Channel Inhibitors in Cancer Cells

Nishino

Tanamachi

Nakanishi

et al. 2016

Biological & Pharmaceutical Bulletin

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Radiosensitizers are used in cancer therapy to increase the γ-irradiation susceptibility of cancer cells, including radioresistant hypoxic cancer cells within solid tumors, so that radiotherapy can be applied at doses sufficiently low to minimize damage to adjacent normal tissues. Radiation-induced DNA damage is repaired by multiple repair systems, and therefore these systems are potential targets for radiosensitizers. We recently reported that the transient receptor potential vanilloid type 1 (TRPV1) channel is involved in early responses to DNA damage after γ-irradiation of human lung adenocarcinoma A549 cells. Therefore, we hypothesized that TRPV1 channel inhibitors would have a radiosensitizing effect by blocking repair of radiation-induced cell damage. Here, we show that pretreatment of A549 cells with the TRPV1 channel inhibitors capsazepine, AMG9810, SB366791 and BCTC suppressed the γ-ray-induced activation of early DNA damage responses, i.e., activation of the protein kinase ataxia-telangiectasia mutated (ATM) and accumulation of p53-binding protein 1 (53BP1). Further, the decrease of survival fraction at one week after γ-irradiation (2.0 Gy) was enhanced by pretreatment of cells with these inhibitors. On the other hand, inhibitor pretreatment did not affect cell viability, the number of apoptotic or necrotic cells, or DNA synthesis at 24 h after irradiation. These results suggest that inhibition of DNA repair by TRPV1 channel inhibitors in irradiated A549 cells caused gradual loss of proliferative ability, rather than acute facilitation of apoptosis or necrosis. TRPV1 channel inhibitors could be novel candidates for radiosensitizers to improve the efficacy of radiation therapy, either alone or in combination with other types of radiosensitizers. Key words γ-ray; radiosensitizer; transient receptor potential vanilloid type 1 channelRadiation therapy plays an important role in treatment of numerous cancers, 1) because ionizing radiation induces potentially lethal DNA damage, such as DNA double-strand breaks (DSBs). Although DSBs cause cell death or genomic instability, 2,3) they can be repaired by mechanisms such as non-homologous end joining (NHEJ) or homologous recombination (HR). NHEJ rejoins the DNA ends without requiring sequence homologies, and is mediated by a DNA-dependent protein kinase holoenzyme. On the other hand, HR processes use undamaged homologous DNA sequences (sister chromatid or the homologous chromosome) to ensure the fidelity of the repair process. [4][5][6] The DNA damage response pathways protect genomic integrity and act as a barrier against cancer, 7) and are important for recovery of irradiated normal cells. However, overexpression of DNA repair proteins is involved in radioresistance of cancer cells, [8][9][10] and therefore these mechanisms also decrease the efficiency of radiation therapy.Since ionizing radiation does not discriminate between cancer cells and normal cells, damage to normal tissues is usually a dose-limiting factor in radiation therapy. In addition, many solid ...

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Modeling the biological response of normal human cells, including repair processes, to fractionated carbon beam irradiation

Cited by 16 publications

References 31 publications

Evaluation of the safety and efficacy of carbon ion radiotherapy for locally advanced adenoid cystic carcinoma of the tongue base

Evaluation of the safety and efficacy of carbon ion radiotherapy for locally advanced adenoid cystic carcinoma of the tongue base

DNA Double-strand Breaks Induced byFractionated Neutron Beam Irradiation for Boron Neutron Capture Therapy

Radiosensitizing Effect of TRPV1 Channel Inhibitors in Cancer Cells

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