No, Is the Subject Area "Gamma radiation" applicable to this article? Our findings are in agreement with previous studies that have reported the lack of a bystander effect on neutron exposure using clonogenic cell survival assay in a human skin cell line [29] and zebrafish [56]. Cells grown in ICCM from irradiated cells showed no significant increase in the frequencies of micronuclei or nucleoplasmic bridges compared to cells grown in ICCM from sham irradiated cells for either cell line. 1s, pp. As expected, high doses of photons induced a clear bystander effect in both cell lines for micronuclei and bridges (p<0.0001). The excess stain was removed by washing in 1X PBS for 1 minute. Copyright: © 2014 Seth et al. Properties of greatest concern are swelling, creep, helium embrittlement, and thermal conductivity degradation (see Nuclear Reactor Materials: Irradiation Effects ). Different responses to neutrons were observed in the two cell lines we used. Cells in T-25 flasks with culture medium were placed on top of 2 cm of water-equivalent material and irradiated at 0.6 Gy/min from below (gantry at 180 degree) using an open 28.8×28.8 cm2 field (SSD of 148 cm). This study used cells that lack gap junctions. Recently, radiation-induced bystander cells were shown to rescue irradiated cells through intercellular feedback. To ensure that the bystander effect observed was actually due to signals produced by the irradiated cells rather than an effect of exposure of the culture medium or an artifact of the media transfer process, a media-only control was included in which fresh media without cells was irradiated at the highest dose (4 Gy) prior to being transferred to non-irradiated cells. Ionizing radiation leads to chromosome damage of the type seen in cancer cells. here. Yes [71] reported RBEs of 2.35 and 2.42 for fast neutrons in immature rat hippocampal cells, as determined by two different cell viability assays. Neutron radiation is also associated with a greater incidence of laryngeal necrosis. Here we used the cytokinesis-block micronucleus assay to address the question whether neutrons induce a bystander effect in normal human lymphoblastoid cell lines. Side Effects of Gamma Radiation. The same set of analyses were performed for the neutron bystander data which included replicate experiments as an additional variable. The frequencies of micronuclei and bridges appear to saturate at higher doses, indicating that multiple chromosome fragments were packaged in some micronuclei, and that more than one dicentric might have contributed to some bridges. The Nuclear Division Indices (NDI) for all experimental conditions were high enough to enumerate micronuclei and bridges, with the exception of cells irradiated with the highest two neutron doses (3 Gy and 4 Gy). These results may be relevant to radiation therapy with fast neutrons and for regulatory agencies setting standards for neutron radiation protection and safety. No, Is the Subject Area "Photons" applicable to this article? Natural radiation is often beneficial to plant growth 3⭐⭐This is a verified and trusted source Goto Source . As a positive control for the bystander effect, cells were exposed to 0 (sham), 0.5, 1, 2, 3 and 4 Gy cobalt-60 gamma rays. Radiation exists all around us, from both natural and manmade sources, and is in two forms: ionizing and non-ionizing radiation. Contributed reagents/materials/analysis tools: IS JLS RDS RE MCJ JDT. 128, No. The experiments described here provide no cytogenetic evidence that fast neutrons are capable of inducing a bystander effect through medium-borne factors. Discover a faster, simpler path to publishing in a high-quality journal. micronuclei and nucleoplasmic bridges, compared to the controls no treatment condition caused any statistically significant change in the frequencies for either of the replicate experiments (p>0.05). Our observation of an absence of a bystander effect following doses of photons that are associated with exposure to neutrons confirmed that there is a lack of a bystander effect in response to neutrons, regardless of the presence of photons. When the biological responses for both radiation types are linearly related to dose, as seen here, the RBE is also the ratio of the biological effects at the same dose. Ionizing radiation is also an effective method for treating tumors because it can be localized to the tumor and is a potent inducer of DNA double-strand breaks, a highly toxic form of DNA damage. Experiments in mice examining carcinogenic effects of single doses of 1.5 MeV neutrons were compared with 250 kVp X-rays, and effects of fractionation were also described. Department of Radiation Oncology, Wayne State University, Detroit, Michigan, United States of America, * E-mail: jtucker@biology.biosci.wayne.edu. The RBE of neutrons for all doses and both cell lines is 2.0±0.13 for micronuclei and 5.8±2.9 for bridges (Table 4), indicating that neutrons are 2 to nearly 6 times more effective in damaging these cells compared to cobalt-60 gamma rays. Yes Ionizing radiation is also an effective method for treating tumors because it can be localized to the tumor and is a potent inducer of DNA double-strand breaks, a highly toxic form of DNA damage. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. S103-S110. After irradiation with fast neu­ trons the incidence of tumours of the testicles, the large intestine, the kidneys and the liver is increased at doses between 42. Beta particles(electrons) are much small… Upon arrival, the flasks were immediately placed upright in a fully humidified 5% CO2 incubator at 37°C, and their caps were loosened. Free neutrons have an half-life of 12 minutes. For GM15510 cells, although the micronuclei frequencies show substantial variation, there clearly is not any consistent evidence of a bystander effect. Wang et al. We also included a media-only control containing fresh media without cells, which was irradiated at the highest dose, i.e. For neutron irradiations, the cells in culture medium in T-25 flasks were irradiated at room temperature with doses 0 (sham), 0.5, 1, 1.5, 2, 3 and 4 Gy. For the direct damage and the bystander effect experiments, three different controls were used: pre-radiation, post-radiation, and transportation control. Yes The average energy and neutron mean free path varies with field size and water-equivalent depth (nominal depth of maximum dose is 1.5 cm). The final concentration of DMSO in each culture was 1.1%. The CNTS generates fast neutrons by targeting a near monoenergetic 50.5 MeV proton beam at a Be target (10.5 mm thick with a radius of 0.635 cm). Four case series and a new case report have been published reporting the impact of HBOT as a treatment for radiation necrosis of the larynx. Unlike low-LET radiation, for high-LET radiation there is also a reduction in the differential radiosensitivity of cells related to their position in cell cycle [60]. For every dose, two flasks were irradiated per cell line: one flask was used to assess the damage induced by direct radiation exposure and the other flask was used for medium transfer for the bystander effect as described below. Η. Chadwick Discussion 161 Differential effects of electrons and neutrons on cell killing and ability of DNA-membrane complex to synthesize DNA in E_. C. Medvedovsky and B. V. Worgul (1991) Neutron Effects on the Lens.Radiation Research: October 1991, Vol. Cells that do not absorb radiation directly may nevertheless be damaged or altered in ways that do not become apparent for many cell generations. Yang et al. Neutron radiation — consisting of free neutrons which are released during fission but not usually through radioactive decay. Cell culture was performed using the standardized protocol provided by Coriell. [59] found that transplantation of a mixture of neutron irradiated and unirradiated bone marrow cells into mice induced instability in the descendants of unirradiated cells as confirmed by measuring chromosomal aberrations, indicating that neutrons induce a bystander effect. Affiliation Normal human lymphoblastoid cell lines (GM15036 and GM15510) obtained from the Coriell Cell Repository were used for these experiments because they have previously been shown to exhibit a bystander effect in response to gamma radiation [22], [24]. Radiation - Radiation - Effects on organs of the body (somatic effects): A wide variety of reactions occur in response to irradiation in the different organs and tissues of the body. The transportation control involved flasks that were transported with the cells that were irradiated, but remained inside the insulated box; these control flasks were further insulated with bubble wrap to maintain their temperature close to 37°C. e98947. Cell culture for all the gamma radiation experiments was performed at Wayne State University (WSU), Detroit, Michigan. 5 and 85 rad. GM15036 cells that received ICCM from any dose greater than 0 had frequencies of micronuclei that were similar to each other, and all were lower than the 0-dose values, although the differences were not statistically significant. The increases for both micronuclei and bridges with dose were significant with and without considering the 4 Gy data point (p<0.0001). [40] observed a significant decrease in the number of DNA double-strand breaks, micronuclei frequencies, and the extent of apoptosis in irradiated cells that were co-cultured with unirradiated bystander cells. The Be target system used to generate fast neutrons also delivers a photon dose of about 5% of the neutron dose, which raises the possibility that any bystander effect observed in the experiments could be due to photons rather than to the neutrons. These cells were exposed to fast neutrons produced by targeting a near-monoenergetic 50.5 MeV proton beam at a Be target (17 MeV average neutron energy), and irradiated-cell conditioned media (ICCM) was transferred to unirradiated cells. The Tukey HSD test was used for post-hoc evaluations. Radiation refers to the energy traveling through space in the form of waves or particles. This is due largely to the increased ionization that takes place near the track a particle of space radiation takes through a material. Following exposure the flasks were returned immediately to the laboratory and incubated for 28 hours. Ionizing radiation carries more than 10eV and includes alpha, beta, and gamma radiation along with x-rays and cosmic rays. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Cellular recognition of DNA damage and the subsequent repair processes may differ between neutrons and photons. No conclusive cytogenetic evidence exists to support or refute the existence of non-targeted effects in cellular responses to neutrons. The flasks were left undisturbed for 24 hours after which the cells were counted and checked for viability using a hemocytometer and trypan blue staining. The authors thank Zainab Hammoud for assisting with the microscopy and Geoffrey Linn for his technical support. Know the harmful effects of radiation & how its exposure can have different effects on … Since the three 0-dose controls (i.e., pre-radiation, post-radiation, and transportation control) for micronuclei and for nucleoplasmic bridges were not statistically different from each other as determined by ANOVA, we report only the pooled control values for these endpoints. broad scope, and wide readership – a perfect fit for your research every time. Ionizing radiation can travel unseen and pass through these materials. These numbers clearly indicate that the RBEs for neutrons vary with the biological system, neutron energy and the end-point. One of the major paradigm shifts in the field of radiation biology was the discovery of non-targeted effects such as the bystander effect in which cells in the vicinity of radiation-damaged cells behave as though they were also irradiated [16]–[20]. How can ionizing radiation cause cancer? Wrote the paper: IS JLS RDS RE MCJ JDT. Therefore, the risks of ionizing radiation need to be analyzed in terms of both direct and non-targeted effects. This observation is in agreement with other reports [55], [68], [69]. Neutron effects in humans: protection considerations. https://doi.org/10.1371/journal.pone.0098947, Received: March 6, 2014; Accepted: May 9, 2014; Published: June 4, 2014. Some of the candidate intercellular signaling molecules that have been implicated in bystander effects are reactive oxygen species [20], [38], reactive nitrogen species [20], [38], nitric oxide [27], [38], cytokines such as TGFβ and interleukin 8 [39], and small molecules such as amino acids [37], [40], [41]. Nuclear radiation arises from hundreds of different kinds of unstable atoms. The results, shown in Figure 3, indicate that these low doses of photons did not produce a bystander effect. Finally, neutrons had a relative biological effectiveness of 2.0±0.13 for micronuclei and 5.8±2.9 for bridges compared to cobalt-60. 47–51 In these five reports, most patients were treated for severe laryngeal necrosis (Chandler grade 3 or 4). The same is true for tumours of the skin and subcutaneous tissue at a dose of 85 rad. For the neutron radiation experiments, cells were grown at WSU up to a concentration of 1×106 cells/mL, then non-vented T-25 flasks were completely filled with media (60 ml) containing cells at this concentration. https://doi.org/10.1371/journal.pone.0098947.g003. Media from these flasks was transferred to non-irradiated cells in the same manner as described for media transfer from flasks that contained cells. However, other studies have reported contrasting results. No, Is the Subject Area "Nucleons" applicable to this article? Micronuclei were required to be no more than one-third the size of the nuclei, and to be round or oval with smooth edges and stained the same color as the nuclei. Cells were then evaluated simultaneously for micronuclei, nucleoplasmic bridges and buds according to our “relaxed” criteria [76]. In contrast, there was no statistically significant bystander component for neutrons (data not shown). coli B/r and Bs-1 (IAEA-SM-179/11) 165 W. A. Cramp, P.E. Cells treated with ICCM from neutron irradiated cells did not show significant increases in micronuclei frequencies compared to sham treated controls for either replicate experiment and for either cell line (Figure 2). Other sources of low level neutron irradiation may include occupational exposure to workers at nuclear power plants and accelerator facilities, astronauts, airline crews and passengers on high altitude flights [3]–[14], as well as radiation incidents such as the Hiroshima-Nagasaki atomic bomb explosions and the tsunami-induced radiation leak at the Fukushima Daiichi site in Japan [15]. Since serotonin has been reported to play a role in the bystander effect [49] and is light sensitive, the bottles containing the culture media were wrapped in aluminum foil and stored in the dark. No, PLOS is a nonprofit 501(c)(3) corporation, #C2354500, based in San Francisco, California, US, https://doi.org/10.1371/journal.pone.0098947. All cultures were grown and maintained in a fully humidified 5% CO2 incubator at 37°C. To ensure that no cells were transferred along with the media, the supernatant was then passed through 0.22 µm polyethylsulfonate syringe filters (Nalgene). There is a possibility that a neutron-induced bystander effect requires physical contact between cells, which could be tested by performing experiments using cell lines such as fibroblasts and keratinocytes that have gap junctions. Understanding the biological effects of neutrons may also enable more refined evaluations of the standards for radiation protection and safety. The bystander components in the total dose response of cobalt-60 gamma rays ranged from approximately 4% to 35% for micronuclei; for bridges, the bystander components ranged up to 6% for GM15510 cells and up to 23% for GM15036 cells (Tables 2 and 3). Gamma radiation is the most penetrative type of energy currently known. Here we asked whether neutrons also induce a bystander effect in two normal human lymphoblastoid cell lines. In health physics, neutron radiation is a type of radiation hazard. Severe Radiation Sickness Larger acute doses of gamma radiation, or larger doses that accumulate over time, can lead to much more severe symptoms. To rule out this possibility, cells were acutely irradiated with cobalt-60 gamma rays at doses equivalent to the 5% of the delivered neutron dose, i.e. Yes No, Is the Subject Area "Malignant tumors" applicable to this article? The media-only control had values similar to the 0 Gy (control) for both endpoints. To reaffirm that the experimental conditions used here are capable of seeing a direct (i.e. The results shown here suggest that contaminating photons are not a likely confounding factor that interfered with the ability to detect a neutron-induced bystander effect. Relating dose to radiation effects in humans and other large mammals is further complicated by the fact that mixed-spectrum radiations change as they interact with body tissue. While much has been learned about x-ray and gamma-ray effects on cells and whole organisms, less is known about the biological effects of neutrons. The cytokinesis-block micronucleus assay was used to quantify genetic damage in radiation-naïve cells exposed to ICCM from cultures that received 0 (control), 0.5, 1, 1.5, 2, 3 or 4 Gy neutrons. The measurements indicate that the neutron RBE for directly damaged cells compared to cobalt-60 gamma rays is 2.0±0.13 for micronuclei and 5.8±2.9 for bridges. For each treatment (i.e., cell line and dose group) the left-hand bar in each pair is replicate 1 and the right-hand bar is replicate 2. [72] used the cytokinesis-block micronucleus assay and a cell survival assay in a human colon carcinoma cell line and observed an RBE of 4.4 for neutrons in boron neutron capture therapy. Another possible explanation for the lack of a bystander effect with neutrons observed in this study may be the presence of dimethyl sulfoxide (DMSO), a scavenger of reactive oxygen species [64], [65], which was used to dissolve cytochalasin B that is required for the cytokinesis-block micronucleus assay. A very high level of radiation exposure delivered over a short period of time can cause symptoms such as nausea and vomiting within hours and can sometimes result in death over the following days or weeks. Neutrons should be changed from 10 to 20 the standardized protocol provided by Coriell once each different... The harmful effects of radiation interacts with matter in a high-quality journal may 9, 2014 ; Accepted: 9., only binucleated cells ( table 1 ) DNA, cells and tissues, there is... 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