Radiation-induced bystander effects (RIBE) are discussed as relevant processes during radiotherapy. Irradiated cells are suggested to release growth-inhibitory/DNA-damaging factors transported to ...non-irradiated cells. However, the molecular nature of this phenomenon has not yet been resolved. We aimed at identifying the growth-inhibitory factor(s) transmitted to non-irradiated cells.
RIBE-competent PC3 cells were used to produce conditioned medium (CM) after exposure to ionizing radiation. Indicator cells were incubated with CM and clonogenic survival as well as cell proliferation were determined as endpoints. A549 indicator cells exhibited a bystander effect upon incubation with CM from irradiated PC3 cells. This bystander effect was not due to DNA-damaging factors, but a radiation-triggered reduction of mitogenic/clonogenic activity present in CM.
Several tumor cells, but not normal fibroblasts secrete this factor, whose release is reduced by irradiation. We identified L-Plastin to be responsible for the mitogenic/clonogenic activity. Removal of L-Plastin from CM by immunoprecipitation or siRNA-mediated knockdown of L-Plastin expression resulted in loss or reduction of mitogenic/clonogenic activity transmitted via CM, respectively. Exosome-transported L-Plastin was constitutively Ser5-phosphorylated, indicative of its bioactive conformation.
In summary, we observed production and exosomal secretion of L-Plastin by cancer cells. Via exosome-transmitted L-Plastin, tumors induce clonogenic and mitogenic activity in cancer and normal cells of the tumor microenvironment. Irradiation inhibits L-Plastin production targeting both cancer cells and the tumor niche and may explain the high impact of radiotherapy in tumor control.
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•Bystander cells have reduced clonogenic survival, but no increase in DNA damage.•L-Plastin exerts strong clonogenic activity in an autocrine and paracrine manner.•Different malignant cells, but not normal fibroblasts secrete clonogenic L-Plastin.•Reduced exosomal L-Plastin is responsible for the observed bystander effect.•Exosomal L-Plastin is constitutively phosphorylated at Ser5.
The purpose of this study was to investigate the effects of astragalus polysaccharides (APS) on the proliferation and apoptosis of bone marrow mesenchymal stem cells (BMSCs) induced by X-ray ...radiation-induced A549 cells bystander effect (RIBE), and to explore their mechanisms. In this study, APS increased the reduced cell proliferation rate induced by RIBE and inhibiting the apoptosis of bystander cells. In terms of mechanism, APS up-regulates the proteins Bcl-2, Bcl-xl, and down-regulates the proteins Bax and Bak, which induces a decrease in mitochondrial membrane potential, which induces the release of Cyt-c and AIF, which leads to caspase-dependent and caspase-independent pathway to cause apoptosis. In addition, we believe that ROS may be the main cause of these protein changes. APS can inhibit the generation of ROS in bystander cells and thus inhibit the activation of the mitochondrial pathway, further preventing cellular damage caused by RIBE.
Recent discoveries of rapid changes in the atmospheric
C concentration linked to solar particle events have spurred the construction of new radiocarbon annual calibration datasets
. With these ...datasets, radiocarbon dating becomes relevant for urban sites, which require dates at higher resolution than previous calibration datasets could offer. Here we use a single-year radiocarbon calibration curve to anchor the archaeological stratigraphy of a Viking Age trade centre in time. We present absolutely dated evidence for artefact finds charting the expansion of long-distance trade from as far away as Arctic Norway and the Middle East, which we linked to the beginning of the Viking Age at AD 790 ± 10. The methods developed here enable human interactions and cultural, climatic and environmental changes to be compared in archaeological stratigraphies worldwide.
Alohtona fauna parazita slatkovodnih vrsta riba nije detaljno istražena u Republici Hrvatskoj unatoč dugoj povijesti unosa i prijenosa stranih vrsta riba u kopnene vode. Negativne posljedice za ...proizvodnju u akvakulturi i divlje vrste riba često su povezivane s unosom alohtonih vrsta parazita. Stoga ovaj članak nastoji izložiti povijesni pregled lokacija, vremenskih perioda i načina unosa alohtonih vrsta parazita riba u kopnene vode i time sastaviti listu vrsta. Ukupno, 16 alohtonih vrsta parazita zabilježeni su u kopnenim vodama Republike Hrvatske, a ribnjačarstva i ribogojilišta su utvrđena kao početne točke njihovog unosa. Međutim, postoji malo objavljenih podataka o ukupnoj prevalenciji infekcija, kao i ekonomskom utjecaju na akvakulturnu proizvodnju. Osim toga, ograničene informacije su dostupne o prisutnosti i potencijalnom ekološkom utjecaju egzotičnih parazita na autohtone vrste, posebno na endemsku ihtiofaunu u područjima visoke biološke raznolikosti, poput vodenih tijela Jadranskog slijeva. Stoga, postoji žurna i nužna potreba za multidisciplinarni pristup u suradnji između različitih dionika, uključujući državne institucije i znanstvene institucije u biološkoj, poljoprivrednoj i u veterinarskoj disciplini te sektora proizvodnje, s ciljem opsežnih istraživanja kako bi se utvrdio potencijalni utjecaj na proizvodnju akvakulture te autohtone populacije riba visoke konzervacijske vrijednosti.
•Cell cycle status of irradiated cells was involved in the bystander effect induced by carbon ions.•Targeted cells in G2-M phase had the largest contribution to the bystander effect.•DNA-PKcs and ATM ...co-regulated radiation induced G2-M phase-related bystander effect.
Accumulated evidence has shown that radiation-induced bystander effect (RIBE) may have significant implications to the efficiency of radiotherapy. Although cellular radiosensitivity relies on cell cycle status, it is largely unknown how about the relationship between RIBE and cell cycle distribution, much less the underlying mechanism. In the present study, the lung cancer A549 cells were synchronized into different cell cycle phases of G1, S and G2/M and irradiated with high linear energy transfer (LET) carbon ions. By treating nonirradiated cells with the conditioned medium from these irradiated cells, it was found that the G2-M phase cells had the largest contribution to RIBE. Meanwhile, the activity of DNA-PKcs but not ATM was increased in the synchronized G2-M phase cells in spite of both of them were activated in the asynchronous cells after carbon ion irradiation. When the G2-M phased cells were transferred with DNA-PKcs siRNA and ATM siRNA individually or treated with an inhibitor of either DNA-PKcs or ATM before carbon ion irradiation, the RIBE was effectively diminished. These results provide new evidence linking cell cycle to bystander responses and demonstrate that DNA-PKcs and ATM are two associated factors in co-regulating G2-M phase-related bystander effects.
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•Control of radicals that cannot be controlled in plasma using a exhaust system.•Reduces the amount of radicals reacting to the pattern sidewall in the dry etching.•To analyze changes ...in ions and radicals in the process of radial control.
Radicals generated during reactive ion etching (RIE) cannot be electrically controlled, causing isotropic etching and chemical damage to the sidewall of the etched feature during the etching process. In this study, using a reactive ion beam etcher (RIBE) installed with a dual exhaust system, where an additional exhaust valve was introduced to pump out radicals from the inductively coupled plasma (ICP) source chamber in addition to the conventional main gate valve in the process chamber, the radical flux relative to ion flux during the RIE process has been controlled and the effect of additional exhausting through the ICP source chamber for the control of radical flux relative to ion flux on the properties of etching has been investigated using CF4 gas. The results showed that the additional exhausting of the radicals through the ICP source chamber not only decreased the ICP source chamber pressure but also decreased the ratio of radical flux to ion flux to the substrate. The lower ICP source chamber pressure could be also obtained without additional exhausting through the ICP source chamber by decreasing the CF4 gas flow rate to the ICP source chamber, however, the lower ratio of radical flux to ion flux was observed for the dual exhaust system. It is believed that, for the next generation RIBE, multiple exhausting is beneficial for anisotropic etching of nanoscale features by controlling the radical flux to the sidewall and ion flux to the bottom of a nanoscale feature during the etching.
Micro‐X‐ray fluorescence (XRF) screening of 244 glass sherds from Ribe, Denmark, identified 23 wood ash glasses. The closely dated finds pinpoint the arrival of the earliest wood ash glass produced ...in Western Europe in this important North Sea trading hub. This glass type was absent among glass from 700 to 790 CE but feature strongly from 790 to 810 CE. Electron microprobe analysis (EMPA) and laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) analysis of 24 glasses show the presence of four types. We show the strengths of classifying wood ash glass based on the glass‐producing sands and conclude that the earliest production took place on a considerable scale and had a major impact on glass circulation in Northern Europe in the ninth century.
Synchrotron radiation, especially microbeam radiotherapy (MRT), has a great potential to improve cancer radiotherapy, but non-targeted effects of synchrotron radiation have not yet been sufficiently ...explored. We have previously demonstrated that scattered synchrotron radiation induces measurable
γ
-H2AX foci, a biomarker of DNA double-strand breaks, at biologically relevant distances from the irradiated field that could contribute to the apparent accumulation of bystander DNA damage detected in cells and tissues outside of the irradiated area. Here, we quantified an impact of scattered radiation to DNA damage response in “naïve” cells sharing the medium with the cells that were exposed to synchrotron radiation. To understand the effect of genetic alterations in naïve cells, we utilised p53-null and p53-wild-type human colon cancer cells HCT116. The cells were grown in two-well chamber slides, with only one of nine zones (of equal area) of one well irradiated with broad beam or MRT.
γ
-H2AX foci per cell values induced by scattered radiation in selected zones of the unirradiated well were compared to the commensurate values from selected zones in the irradiated well, with matching distances from the irradiated zone. Scattered radiation highly impacted the DNA damage response in both wells and a pronounced distance-independent bystander DNA damage was generated by broad-beam irradiations, while MRT-generated bystander response was negligible. For p53-null cells, a trend for a reduced response to scattered irradiation was observed, but not to bystander signalling. These results will be taken into account for the assessment of genotoxic effects in surrounding non-targeted tissues in preclinical experiments designed to optimise conditions for clinical MRT and for cancer treatment in patients.
The radiation-induced bystander effect (RIBE) is the initiation of biological end points in cells (bystander cells) that are not directly traversed by an incident-radiation track, but are in close ...proximity to cells that are receiving the radiation. RIBE has been indicted of causing DNA damage via oxidative stress, besides causing direct damage, inducing tumorigenesis, producing micronuclei, and causing apoptosis. RIBE is regulated by signaling proteins that are either endogenous or secreted by cells as a means of communication between cells, and can activate intracellular or intercellular oxidative metabolism that can further trigger signaling pathways of inflammation. Bystander signals can pass through gap junctions in attached cell lines, while the suspended cell lines transmit these signals via hormones and soluble proteins. This review provides the background information on how reactive oxygen species (ROS) act as bystander signals. Although ROS have a very short half-life and have a nanometer-scale sphere of influence, the wide variety of ROS produced via various sources can exert a cumulative effect, not only in forming DNA adducts but also setting up signaling pathways of inflammation, apoptosis, cell-cycle arrest, aging, and even tumorigenesis. This review outlines the sources of the bystander effect linked to ROS in a cell, and provides methods of investigation for researchers who would like to pursue this field of science.
It is well established that cells, tissues, and organisms exposed to low doses of ionizing radiation can induce effects in non-irradiated neighbors (non-targeted effects or NTE), but the mechanisms ...remain unclear. This is especially true of the initial steps leading to the release of signaling molecules contained in exosomes. Voltage-gated ion channels, photon emissions, and calcium fluxes are all involved but the precise sequence of events is not yet known. We identified what may be a quantum entanglement type of effect and this prompted us to consider whether aspects of quantum biology such as tunneling and entanglement may underlie the initial events leading to NTE. We review the field where it may be relevant to ionizing radiation processes. These include NTE, low-dose hyper-radiosensitivity, hormesis, and the adaptive response. Finally, we present a possible quantum biological-based model for NTE.
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