Enhanced DNA double-strand break repair of microbeam targeted A549 lung carcinoma cells by adjacent WI38 normal lung fibroblast cells via bi-directional signaling

Kobayashi, Adam; Ahmad, Tengku Ahbrizal Farizal Tengku; Autsavapromporn, Narongchai; Oikawa, Masakazu; Homma-Takeda, Shino; Furusawa, Yoshiya; Wang, Jun; Konishi, Teruaki

doi:10.1016/j.mrfmmm.2017.06.006

Cited by 26 publications

(41 citation statements)

References 32 publications

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“…In 2011, RIRE was demonstrated between human primary fibroblast (NHLF) and human cervical cancer (HeLa) cells [ 1 ]. RIRE has since attracted extensive interest in the research community, and has been successfully demonstrated in different in vitro [ 2 – 10 ] and in vivo [ 11 , 12 ] experiments. A review summarized recent studies on RIRE, as well as possible mechanisms and the involved chemical messengers [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Induction of autophagy and interleukin 6 secretion in bystander cells: metabolic cooperation for radiation-induced rescue effect?

Kong

Cheng

2018

Journal of Radiation Research

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We hypothesized that radiation-induced rescue effect (RIRE) shared similar mechanisms with ‘metabolic cooperation’, in which nutrient-deprived cancer cells prompted normal cells to provide nutrients. Our data demonstrated that X-ray irradiation induced autophagy in HeLa cells, which could last at least 18 h, and proved that the irradiated cells (IRCs) resorted to breaking down their own intracellular components to supply the molecules required for cell-repair enhancement (e.g. to activate the NF-κB pathway) in the absence of support from bystander unirradiated cells (UICs). Furthermore, autophagy accumulation in IRCs was significantly reduced when they were partnered with UICs, and more so with UICs with pre-induced autophagy before partnering (through starvation using Earle’s Balanced Salt Solution), which showed that the autophagy induced in UICs supported the IRCs. Our results also showed that interleukin 6 (IL-6) was secreted by bystander UICs, particularly the UICs with pre-induced autophagy, when they were cultured in the medium having previously conditioned irradiated HeLa cells. It was established that autophagy could activate the signal transducer and activator of transcription 3 (STAT3) that was required for the IL-6 production in the autophagy process. Taken together, the metabolic cooperation of RIRE was likely initiated by the bystander factors released from IRCs, which induced autophagy and activated STAT3 to produce IL-6 in bystander UICs, and was finally manifested in the activation of the NF-κB pathway in IRCs by the IL-6 secreted by the UICs.

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Section: Introductionmentioning

confidence: 99%

Induction of autophagy and interleukin 6 secretion in bystander cells: metabolic cooperation for radiation-induced rescue effect?

Kong

Cheng

2018

Journal of Radiation Research

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“…Genomic DNA damage can be caused directly by the radiation beam, or indirectly by the formation of reactive radical species. Within the past two decades, evidence from microbeam‐based studies showed that cytoplasm irradiation leads to DNA damage in the target cell, as well as in bystander cells . Elevated reactive radical species are considered one of the core reasons for such damage.…”

Section: Discussionmentioning

confidence: 99%

“…Within the past two decades, evidence from microbeam-based studies showed that cytoplasm irradiation leads to DNA damage in the target cell, 21 as well as in bystander cells. 22 Elevated reactive radical species are considered one of the core reasons for such damage. Treatment with ROS scavenger DMSO largely decreased the mutation frequency of gene CD59 in A L cells irradiated by 4α particles in the cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

Nuclear factor (erythroid‐derived 2)‐like 2 antioxidative response mitigates cytoplasmic radiation‐induced DNA double‐strand breaks

Wang

Konishi

2019

Cancer Science

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It has been reported that DNA double‐strand breaks (DSB) can be induced by cytoplasm irradiation, and that both reactive free radicals and mitochondria are involved in DSB formation. However, the cellular antioxidative responses that are stimulated and the biological consequences of cytoplasmic irradiation remain unknown. Using the Single Particle Irradiation system to Cell (SPICE) proton microbeam facility at the National Institute of Radiological Sciences ([NIRS] Japan), the response of nuclear factor (erythroid‐derived 2)‐like 2 (NRF2) antioxidative signaling to cytoplasmic irradiation was studied in normal human lung fibroblast WI‐38 cells. Cytoplasmic irradiation stimulated the localization of NRF2 to the nucleus and the expression of its target protein, heme oxygenase 1. Activation of NRF2 by tert‐butylhydroquinone mitigated the levels of DSB induced by cytoplasmic irradiation. Mitochondrial fragmentation was also promoted by cytoplasmic irradiation, and treatment with mitochondrial division inhibitor 1 (Mdivi‐1) suppressed cytoplasmic irradiation‐induced NRF2 activation and aggravated DSB formation. Furthermore, p53 contributed to the induction of mitochondrial fragmentation and activation of NRF2, although the expression of p53 was significantly downregulated by cytoplasmic irradiation. Finally, mitochondrial superoxide (MitoSOX) production was enhanced under cytoplasmic irradiation, and use of the MitoSOX scavenger mitoTEMPOL indicated that MitoSOX caused alterations in p53 expression, mitochondrial dynamics, and NRF2 activation. Overall, NRF2 antioxidative response is suggested to play a key role against genomic DNA damage under cytoplasmic irradiation. Additionally, the upstream regulators of NRF2 provide new clues on cytoplasmic irradiation‐induced biological processes and prevention of radiation risks.

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“…In 2011, the rescue effect between human primary fibroblast and human cervical cancer (HeLa) cells was revealed [ 1 ]. The rescue effect was subsequently demonstrated in different in vitro [ 2 – 8 ] and in vivo [ 9 , 10 ] experiments. Some studies also demonstrated a deviant rescue effect which led to exacerbated harmful radiobiological effects in the irradiated cells [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Monte Carlo studies on photon interactions in radiobiological experiments

et al. 2018

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X-ray and γ-ray photons have been widely used for studying radiobiological effects of ionizing radiations. Photons are indirectly ionizing radiations so they need to set in motion electrons (which are a directly ionizing radiation) to perform the ionizations. When the photon dose decreases to below a certain limit, the number of electrons set in motion will become so small that not all cells in an “exposed” cell population can get at least one electron hit. When some cells in a cell population are not hit by a directly ionizing radiation (in other words not irradiated), there will be rescue effect between the irradiated cells and non-irradiated cells, and the resultant radiobiological effect observed for the “exposed” cell population will be different. In the present paper, the mechanisms underlying photon interactions in radiobiological experiments were studied using our developed NRUphoton computer code, which was benchmarked against the MCNP5 code by comparing the photon dose delivered to the cell layer underneath the water medium. The following conclusions were reached: (1) The interaction fractions decreased in the following order: 16O > 12C > 14N > 1H. Bulges in the interaction fractions (versus water medium thickness) were observed, which reflected changes in the energies of the propagating photons due to traversals of different amount of water medium as well as changes in the energy-dependent photon interaction cross-sections. (2) Photoelectric interaction and incoherent scattering dominated for lower-energy (10 keV) and high-energy (100 keV and 1 MeV) incident photons. (3) The fractions of electron ejection from different nuclei were mainly governed by the photoelectric effect cross-sections, and the fractions from the 1s subshell were the largest. (4) The penetration fractions in general decreased with increasing medium thickness, and increased with increasing incident photon energy, the latter being explained by the corresponding reduction in interaction cross-sections. (5) The areas under the angular distribution curves of photons exiting the medium layer and subsequently undergoing interactions within the cell layer became smaller for larger incident photon energies. (6) The number of cells suffering at least one electron hit increased with the administered dose. For larger incident photon energies, the numbers of cells suffering at least one electron hit became smaller, which was attributed to the reduction in the photon interaction cross-section. These results highlighted the importance of the administered dose in radiobiological experiments. In particular, the threshold administered doses at which all cells in the exposed cell array suffered at least one electron hit might provide hints on explaining the intriguing observation that radiation-induced cancers can be statistically detected only above the threshold value of ~100 mSv, and thus on reconciling controversies over the linear no-threshold model.

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Enhanced DNA double-strand break repair of microbeam targeted A549 lung carcinoma cells by adjacent WI38 normal lung fibroblast cells via bi-directional signaling

Cited by 26 publications

References 32 publications

Induction of autophagy and interleukin 6 secretion in bystander cells: metabolic cooperation for radiation-induced rescue effect?

Induction of autophagy and interleukin 6 secretion in bystander cells: metabolic cooperation for radiation-induced rescue effect?

Nuclear factor (erythroid‐derived 2)‐like 2 antioxidative response mitigates cytoplasmic radiation‐induced DNA double‐strand breaks

Monte Carlo studies on photon interactions in radiobiological experiments

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