The bystander cell-killing effect mediated by nitric oxide in normal human fibroblasts varies with irradiation dose but not with radiation quality

Yokota, Yuichiro; Funayama, Tomoo; Mutou-Yoshihara, Yasuko; Ikeda, Hiroko; Kobayashi, Yasuhiko

doi:10.3109/09553002.2015.1021960

Cited by 12 publications

(7 citation statements)

References 34 publications

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“…Delayed and persistent radical stress caused by signaling between irradiated cells and unirradiated bystanders is thought to contribute to late cellular effects of irradiation including cell killing (so called bystander effect)9101112. Here, we focus on immediate nitroxidative stress most probably due to water radiolysis, which generates primary radicals with a lifetime in the ns range.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, peroxynitrite results from the reaction of O 2 · − with nitric oxide (NO · )38, which is more likely part of the delayed radiation response that mostly affects cells which have not been directly hit by a radical event (i.e. the bystander effect)9101112. However, the bystander effect cannot have contributed much to the differences in tyrosine nitration observed here, since at the doses investigated, on average, all cells received more than one hit, and as a result, there were very few bystander cells present in the experiments (see Figs 1A and 2A).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, ionising radiation induces delayed responses involving enhanced nitroxidative stress, which is thought to contribute to late and non-targeted effects9101112. The half-life of the primary radicals induced by the interaction of protons with H 2 O, O 2 or NO · is in the ns range91314.…”

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confidence: 99%

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Ultra-short laser-accelerated proton pulses have similar DNA-damaging effectiveness but produce less immediate nitroxidative stress than conventional proton beams

Raschke

Spickermann

Toncian

et al. 2016

Sci Rep

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Ultra-short proton pulses originating from laser-plasma accelerators can provide instantaneous dose rates at least 107-fold in excess of conventional, continuous proton beams. The impact of such extremely high proton dose rates on A549 human lung cancer cells was compared with conventionally accelerated protons and 90 keV X-rays. Between 0.2 and 2 Gy, the yield of DNA double strand breaks (foci of phosphorylated histone H2AX) was not significantly different between the two proton sources or proton irradiation and X-rays. Protein nitroxidation after 1 h judged by 3-nitrotyrosine generation was 2.5 and 5-fold higher in response to conventionally accelerated protons compared to laser-driven protons and X-rays, respectively. This difference was significant (p < 0.01) between 0.25 and 1 Gy. In conclusion, ultra-short proton pulses originating from laser-plasma accelerators have a similar DNA damaging potential as conventional proton beams, while inducing less immediate nitroxidative stress, which probably entails a distinct therapeutic potential.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Ultra-short laser-accelerated proton pulses have similar DNA-damaging effectiveness but produce less immediate nitroxidative stress than conventional proton beams

Raschke

Spickermann

Toncian

et al. 2016

Sci Rep

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“…The protonemata and protoplasts were irradiated with γ-rays [ 13 ]. Irradiation experiments were performed at room temperature in the Cobalt-60 irradiation facility of the Takasaki Advanced Radiation Research Institute (TARRI), National Institutes for Quantum and Radiological Science and Technology (QST), Takasaki, Japan.…”

Section: Methodsmentioning

confidence: 99%

The Moss Physcomitrella patens Is Hyperresistant to DNA Double-Strand Breaks Induced by γ-Irradiation

Yokota

Sakamoto

2018

Genes

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The purpose of this study was to investigate whether the moss Physcomitrella patens cells are more resistant to ionizing radiation than animal cells. Protoplasts derived from P. patens protonemata were irradiated with γ-rays of 50–1000 gray (Gy). Clonogenicity of the protoplasts decreased in a γ-ray dose-dependent manner. The dose that decreased clonogenicity by half (LD50) was 277 Gy, which indicated that the moss protoplasts were 200-times more radioresistant than human cells. To investigate the mechanism of radioresistance in P. patens, we irradiated protoplasts on ice and initial double-strand break (DSB) yields were measured using the pulsed-field gel electrophoresis assay. Induced DSBs linearly increased dependent on the γ-ray dose and the DSB yield per Gb DNA per Gy was 2.2. The DSB yield in P. patens was half to one-third of those reported in mammals and yeasts, indicating that DSBs are difficult to induce in P. patens. The DSB yield per cell per LD50 dose in P. patens was 311, which is three- to six-times higher than those in mammals and yeasts, implying that P. patens is hyperresistant to DSBs. Physcomitrella patens is indicated to possess unique mechanisms to inhibit DSB induction and provide resistance to high numbers of DSBs.

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“…Yokota et al (2015) used gamma rays and carbon ions and found that the bystander effect in their normal fibroblast system depended on nitric oxide and radiation dose, but there was no radiation quality effect. The most significant radiation quality effect appears to concern neutrons where no bystander effect has been reported if the gamma component of the beam is shielded.…”

Section: Introductionmentioning

confidence: 99%

Factors Influencing Effects of Low-dose Radiation Exposure

Mothersill,

Seymour,

Cocchetto

et al. 2024

Health Physics

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It is now well accepted that the mechanisms induced by low-dose exposures to ionizing radiation (LDR) are different from those occurring after high-dose exposures. However, the downstream effects of these mechanisms are unclear as are the quantitative relationships between exposure, effect, harm, and risk. In this paper, we will discuss the mechanisms known to be important with an overall emphasis on how so-called “non-targeted effects” (NTE) communicate and coordinate responses to LDR. Targeted deposition of ionizing radiation energy in cells causing DNA damage is still regarded as the dominant trigger leading to all downstream events whether targeted or non-targeted. We regard this as an over-simplification dating back to formal target theory. It ignores that last 100 y of biological research into stress responses and signaling mechanisms in organisms exposed to toxic substances, including ionizing radiation. We will provide evidence for situations where energy deposition in cellular targets alone cannot be plausible as a mechanism for LDR effects. An example is where the energy deposition takes place in an organism not receiving the radiation dose. We will also discuss how effects after LDR depend more on dose rate and radiation quality rather than actual dose, which appears rather irrelevant. Finally, we will use recent evidence from studies of cataract and melanoma induction to suggest that after LDR, post-translational effects, such as protein misfolding or defects in energy metabolism or mitochondrial function, may dominate the etiology and progression of the disease. A focus on such novel pathways may open the way to successful prophylaxis and development of new biomarkers for better risk assessment after low dose exposures.

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The bystander cell-killing effect mediated by nitric oxide in normal human fibroblasts varies with irradiation dose but not with radiation quality

Abstract: The bystander cell-killing effect mediated by NO radicals in normal human fibroblasts depends on irradiation doses of up to 0.5 Gy, but not on radiation quality. NO radical production appears to be an important determinant of γ-ray- and carbon-ion-induced bystander effects.

Cited by 12 publications

References 34 publications

Ultra-short laser-accelerated proton pulses have similar DNA-damaging effectiveness but produce less immediate nitroxidative stress than conventional proton beams

Ultra-short laser-accelerated proton pulses have similar DNA-damaging effectiveness but produce less immediate nitroxidative stress than conventional proton beams

The Moss Physcomitrella patens Is Hyperresistant to DNA Double-Strand Breaks Induced by γ-Irradiation

Factors Influencing Effects of Low-dose Radiation Exposure

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