Screening of cytokines associated with ionizing radiation dose in serum by cytokine array
Qiong LiuYing HeShen XianrongLinfang MoQingrong WangWei ChenDingwen JiangDengyong HouXiao-yi HeTian-tian QianYuming LiuKexian Li
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Objective To identify the cytokine biomarker candidates in serum associated with ionizing radiation dose, and analyze the patterns of them by cytokine antibody array. Methods Eighty male C57BL/6 mice were randomly divided into radiation group (n=60) and control group (n=20). Mice in radiation group were treated with 60Co total-body irradiation with the dose of 3, 5 and 10Gy, respectively (20 each dose group). Six hours after radiation, blood was obtained from the orbital sinus bleeding, and serums were collected. The serum cytokine concentration was analyzed by antibody array of 96 mouse cytokines, and cytokine biomarker candidates which were shown to be dose-responsive to ionizing radiation had been identified. Results Interestingly, the majority of the 96 mouse cytokines showed positive changes in amounts of cytokine. Following ionizing radiation exposure, only 44 cytokines changed at the expose dose of 3Gy, while 47 cytokines changed at the dose of 5Gy and 66 cytokines at the dose of 10Gy. Further analysis revealed that 14 cytokines were shown to be dose-responsive to ionizing radiation. Among those, 7 cytokines were shown up-regulated in a dose-dependent trend in response to ionizing radiation, and 7 cytokines were shown downregulated. Conclusion These serum cytokine biomarkers which are sensitive to ionizing radiation may act in a dose-dependent manner, suggesting that the serum cytokine biomarker candidates can be used for estimating dose of ionizing radiation.
DOI: 10.11855/j.issn.0577-7402.2013.10.008Cite
The very sensitive Jerne method of detecting the plaque-forming cells was used in the study of the immunosuppressive effect of ionizing radiation on laboratory mice. A significant immunosuppression was obtained after irradiation of the individual groups of mice with 3, 4, 5 and 6 Gy. Successive regeneration of the immunity system occurred after 42 hours only in the groups of mice irradiated with 3 and 4 Gy. mice; ionizing radiation; immunoproductive cells; Jerne method.
Immunosuppression
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Threats of nuclear and other radiologic exposures have been increasing but no countermeasure for acute radiation syndrome has been approved by regulatory authorities. In prior publications we have demonstrated the efficacy of tocopherol succinate (TS) as a promising radiation countermeasure with the potential to protect against lethal doses of ionizing radiation exposure. The aim of this study was to gain further insight regarding how TS protects mice against a lethal dose of radiation. CD2F1 mice were injected subcutaneously with 400 mg/kg of TS, and 24 h later exposed to 60Co γ–radiation. Intestinal tissues or spleen/thymus were harvested after irradiation and analyzed for CD68-positive inflammatory cells and apoptotic cells by immunostaining of jejunal cross-sections. Comet assay was used to analyze DNA damage in various tissues. Phospho-histone H3(pH3) and the proliferating cell nuclear antigen (PCNA) were used as mitotic markers for immunostaining jejunal cross-sections. We observed that injecting TS significantly decreased the number of CD68-positive cells, DNA damage and apoptotic cells (BAX, caspase 3 and cleaved poly(ADP-ribose) polymerase-positive cells) as judged by various apoptotic pathway markers. TS treatment also increased proliferating cells in irradiated mice. Results of this study further support our contention that TS protects mice against lethal doses of ionizing radiation by inhibiting radiation-induced apoptosis and DNA damage while enhancing cell proliferation.
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Objective To study the copy number of genes-components of signaling cascades involved in DNA repair, cell cycle regulation and apoptosis under the influence of high doses of ionizing radiation. Material and М ethods The study was carried out on a culture of H1299 non-small cell lung cancer cells. Cell lines were cultured in a Binder incubator (Germany) for 24 h (at 37 °C, 5% CO2 ), and then the groups were divided into therapeutic and control. The first one was irradiated with a NovalisTx, Varian linear accelerator at doses from 18 to 24 Gy, the second was not exposed to radiation. During the study, we monitored cell viability and evaluated apoptotic activity, then each sample was amplified in two iterations. During the study, cell viability was monitored, apoptotic activity was assessed, and then each sample was amplified in two replicates. The relative copy number of genetic loci was determined by Real-Time qPCR (RT-qPCR). Results When comparing the relative copy number in the genetic loci of the H1299 non-small cell lung cancer cell culture after exposure to a high dose of ionizing radiation, a statistically significant decrease in the relative copy number of the CASP3 and RBBP8 genes was found, which may indicate a decrease in the potential of caspase-mediated tumor repopulation and an increase in the radiosensitivity of tumor cells. Conclusion Exposure to high doses of ionizing radiation leads to a detrimental effect on tumor cells and allows to overcome one of the mechanisms of radioresistance – tumor cell repopulation.
Radioresistance
Radiosensitivity
Viability assay
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Objective To identify the cytokine biomarker candidates in serum associated with ionizing radiation dose,and analyze the patterns of them by cytokine antibody array.Methods Eighty male C57BL/6 mice were randomly divided into radiation group(n=60) and control group(n=20).Mice in radiation group were treated with60Co total-body irradiation with the dose of 3,5 and 10Gy,respectively(20 each dose group).Six hours after radiation,blood was obtained from the orbital sinus bleeding,and serums were collected.The serum cytokine concentration was analyzed by antibody array of 96 mouse cytokines,and cytokine biomarker candidates which were shown to be dose-responsive to ionizing radiation had been identified.Results Interestingly,the majority of the 96 mouse cytokines showed positive changes in amounts of cytokine.Following ionizing radiation exposure,only 44 cytokines changed at the expose dose of 3Gy,while 47 cytokines changed at the dose of 5Gy and 66 cytokines at the dose of 10Gy.Further analysis revealed that 14 cytokines were shown to be dose-responsive to ionizing radiation.Among those,7 cytokines were shown up-regulated in a dose-dependent trend in response to ionizing radiation,and 7 cytokines were shown downregulated.Conclusion These serum cytokine biomarkers which are sensitive to ionizing radiation may act in a dose-dependent manner,suggesting that the serum cytokine biomarker candidates can be used for estimating dose of ionizing radiation.
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Congenic
Ratón
Cumulative dose
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Low doses of ionizing radiation are known to induce adaptive response (AR), which is characterized in most cases by temporary nature, though the possibility of long-term persistence of AR is not ruled out. In this investigation we studied the effect of low doses of gamma-radiation on both high-dose radiation-induced and spontaneous level of cytogenetic damage throughout the life of mice. SHK male mice 2 months old were used. Priming doses of 0.1 and 0.2 Gy (0.125 Gy/min, gamma-radiation from 60Co) were used. A challenging dose of 1.5 Gy (1 Gy/min) was used in the experiments using a routine AR experimental design. The frequency of micronucleated polychromatic erythrocytes in bone marrow cells of primed, primed and challenged, and control groups was assessed at various times of animal life span. It was shown that: a) single low-dose gamma-irradiation induces a cytogenetic AR which can be revealed at 1, 3, 6, 9, 12 months after priming; b) single low-dose gamma-irradiation decreases the cytogenetic damage to a level below the spontaneous rate at the end of lifetime (20 months) of animals; c) ability to induce adaptive response does not depend on the age of animals at the moment of priming irradiation. In conclusion, the mechanisms underlying AR not only protect from chromosome damage induced by high-dose irradiation but also may play a role in spontaneous mutagenesis during aging of animals.
Life span
Priming (agriculture)
Gamma Irradiation
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The effects of low-dose single and continuous whole-body irradiation on immune functions were studied in C57BL/6 mice. Plaque-forming cell reaction of the spleen was found to be stimulated by single doses of x rays in the range of 0.025 to 0.075 Gy and by continuous exposure to gamma rays with a cumulative dose of 0.065 Gy. The reactivity of thymocytes to interleukin 1 showed a dose-dependent depression in the dose range of 0.025 to 0.25 Gy, but there was an increase in cell number in the thymus between doses of 0.025 and 0.10 Gy, resulting in enhancement of reaction of the whole organ. Unscheduled DNA synthesis of spleen cells was stimulated by single irradiation with 0.05 Gy and continuous irradiation with a cumulative dose of 0.13 Gy. The implications of these immunologic changes under low-dose radiation are discussed.
Hormesis
Cumulative dose
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To conduct a literature review of candidate protein biomarkers for individual radiation biodosimetry of exposure to ionizing radiation.Reviewed approximately 300 publications (1973 - April 2006) that reported protein effects in mammalian systems after either in vivo or in vitro radiation exposure.We found 261 radiation-responsive proteins including 173 human proteins. Most of the studies used high doses of ionizing radiation (>4 Gy) and had no information on dose- or time-responses. The majority of the proteins showed increased amounts or changes in phosphorylation states within 24 h after exposure (range: 1.5- to 10-fold). Of the 47 proteins that are responsive at doses of 1 Gy and below, 6 showed phosphorylation changes at doses below 10 cGy. Proteins were assigned to 9 groups based on consistency of response across species, dose- and time-response information and known role in the radiation damage response.ATM (Ataxia telengiectasia mutated), H2AX (histone 2AX), CDKN1A (Cyclin-dependent kinase inhibitor 1A), and TP53 (tumor protein 53) are top candidate radiation protein biomarkers. Furthermore, we recommend a panel of protein biomarkers, each with different dose and time optima, to improve individual radiation biodosimetry for discriminating between low-, moderate-, and high-dose exposures. Our findings have applications for early triage and follow-up medical assessments.
Biodosimetry
Radioresistance
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