Indirect Radiation Effects Research Articles

Environmental effects of ozone depletion and its interactions with climate change: Progress report, 2016.

The Parties to the Montreal Protocol are informed by three Panels of experts. One of these is the Environmental Effects Assessment Panel (EEAP), which deals with two focal issues. The first focus is the effects of UV radiation on human health, animals, plants, biogeochemistry, air quality, and materials. The second focus is on interactions between UV radiation and global climate change and how these may affect humans and the environment. When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than previously believed. As a result of this, human health and environmental issues will be longer-lasting and more regionally variable. Like the other Panels, the EEAP produces a detailed report every four years; the most recent was published as a series of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1-184). In the years in between, the EEAP produces less detailed and shorter Progress Reports of the relevant scientific findings. The most recent of these was for 2015 (Photochem. Photobiol. Sci., 2016, 15, 141-147). The present Progress Report for 2016 assesses some of the highlights and new insights with regard to the interactive nature of the direct and indirect effects of UV radiation, atmospheric processes, and climate change. The more detailed Quadrennial Assessment will be made available in 2018.

Geant4-DNA simulation of DNA damage caused by direct and indirect radiation effects and comparison with biological data.

In this work we present results obtained in the frame of the BioQuaRT project. The objective of the study was the correlation between the number of radiation-induced double strand breaks (DSB) of the DNA molecule and the probability of detecting nuclear foci after targeted microbeam irradiation of cells with protons and alpha particles of different LET. The former were obtained by simulation with new methods integrated into Geant4-DNA that permit calculating the number of DSB in a DNA target model induced by direct and indirect radiation effects. A particular focus was laid in this work on evaluating the influence of different criteria applied to the simulated results for predicting the formation of a direct SSB. Indeed, these criteria have an important impact on the predicted number of DSB per particle track and its dependence with LET. Among the criteria tested in this work, the case that a direct radiation interaction leads to a strand break if the cumulative energy deposited in the backbone part of one nucleotide exceeds a threshold of 17.5 eV leads to the best agreement with the relative LET dependence of number of radiation induced foci. Further calculations and experimental data are nevertheless needed in order to fix the simulation parameters and to help interpreting the biological experimental data observed by immunofluorescence in terms of the DSB complexity.

Radiosensitivity and relative biological effectiveness based on a generalized target model.

By considering both cellular repair effects and indirect effects of radiation, we have generalized the traditional target model, and made it have a linear–quadratic–linear characteristic. To assess the repair capacity–dependent radiosensitivity and relative biological effectiveness (RBE), the generalized target model was used to fit the survival of human normal embryonic lung fibroblast MRC-5 cells in the G0 and G1 phases after various types of radiations. The fitting results indicate that the generalized target model works well in the dose ranges considered. The resulting calculations qualitatively show that the parameter ratio (a/V) in the model could represent the cellular repair capacity. In particular, the significant linear correlations between radiosensitivity/RBE and cellular repair capacity are observed for different slopes of the linear regression curves. These results show that the radiosensitivity and RBE depend on the cellular repair capacity and can be regulated by linear energy transfer. These analyses suggest that the ratio a/V in the generalized target model can also be used for radiation damage assessment in radiotherapy.

The Translationally Controlled Tumor Protein and the Cellular Response to Ionizing Radiation-Induced DNA Damage.

The absorption of ionizing radiation by living cells can directly disrupt atomic structures, producing chemical and biological changes. It can also act indirectly through radiolysis of water, thereby generating reactive chemical species that may damage nucleic acids, proteins, and lipids. Together, the direct and indirect effects of radiation initiate a series of biochemical and molecular signaling events that may repair the damage or culminate in permanent physiological changes or cell death. In efforts to gain insight into the mechanisms underlying these effects, we observed a prominent upregulation of the Translationally Controlled Tumor Protein (TCTP) in low dose/low dose rate 137Cs γ-irradiated cells that was associated with adaptive responses that reduced chromosomal damage to a level lower than what occurs spontaneously. Therefore, TCTP may support the survival and genomic integrity of irradiated cells through a role in the DNA damage response. Consistent with this postulate, TCTP was shown to physically interact with ATM, an early sensor of DNA damage, and to exist in a complex with γH2A.X, in agreement with its distinct localization with the foci of the DNA damage marker proteins γH2A.X, 53BP1, and P-ATM. Cells lacking TCTP failed to repair chromosomal damage induced by γ-rays. Further, TCTP was shown to interact with the DNA-binding subunits, Ku70 and Ku80, of DNA-PK, a major participant in nonhomologous end joining of DNA double strand breaks. Moreover, TCTP physically interacted with p53, and its knockdown attenuated the radiation-induced G1 delay, but prolonged the G2 delay. Here, we briefly review the biochemical events leading to DNA damage by ionizing radiation and to its sensing and repair, and highlight TCTP's critical role in maintaining genomic integrity in response to DNA-damaging agents.

The effect of dimethyl sulfoxide on the induction of DNA strand breaks in plasmid DNA and colony formation of PC Cl3 mammalian cells by alpha-, beta-, and Auger electron emitters (223)Ra, (188)Re, and (99m)Tc.

BackgroundDNA damage occurs as a consequence of both direct and indirect effects of ionizing radiation. The severity of DNA damage depends on the physical characteristics of the radiation quality, e.g., the linear energy transfer (LET). There are still contrary findings regarding direct or indirect interactions of high-LET emitters with DNA. Our aim is to determine DNA damage and the effect on cellular survival induced by 223Ra compared to 188Re and 99mTc modulated by the radical scavenger dimethyl sulfoxide (DMSO).MethodsRadioactive solutions of 223Ra, 188Re, or 99mTc were added to either plasmid DNA or to PC Cl3 cells in the absence or presence of DMSO. Following irradiation, single strand breaks (SSB) and double strand breaks (DSB) in plasmid DNA were analyzed by gel electrophoresis. To determine the radiosensitivity of the rat thyroid cell line (PC Cl3), survival curves were performed using the colony formation assay.ResultsExposure to 120 Gy of 223Ra, 188Re, or 99mTc leads to maximal yields of SSB (80 %) in plasmid DNA. Irradiation with 540 Gy 223Ra and 500 Gy 188Re or 99mTc induced 40, 28, and 64 % linear plasmid conformations, respectively. DMSO prevented the SSB and DSB in a similar way for all radionuclides. However, with the α-emitter 223Ra, a low level of DSB could not be prevented by DMSO. Irradiation of PC Cl3 cells with 223Ra, 188Re, and 99mTc pre-incubated with DMSO revealed enhanced survival fractions (SF) in comparison to treatment without DMSO. Protection factors (PF) were calculated using the fitted survival curves. These factors are 1.23 ± 0.04, 1.20 ± 0.19, and 1.34 ± 0.05 for 223Ra, 188Re, and 99mTc, respectively.ConclusionsFor 223Ra, as well as for 188Re and 99mTc, dose-dependent radiation effects were found applicable for plasmid DNA and PC Cl3 cells. The radioprotection by DMSO was in the same range for high- and low-LET emitter. Overall, the results indicate the contribution of mainly indirect radiation effects for each of the radionuclides regarding DNA damage and cell survival. In summary, our findings may contribute to fundamental knowledge about the α-particle induced DNA damage.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-016-0203-x) contains supplementary material, which is available to authorized users.

Paradigm Shift in Radiation Biology/Radiation Oncology-Exploitation of the "H₂O₂ Effect" for Radiotherapy Using Low-LET (Linear Energy Transfer) Radiation such as X-rays and High-Energy Electrons.

Most radiation biologists/radiation oncologists have long accepted the concept that the biologic effects of radiation principally involve damage to deoxyribonucleic acid (DNA), which is the critical target, as described in “Radiobiology for the Radiologist”, by E.J. Hall and A.J. Giaccia [1]. Although the concepts of direct and indirect effects of radiation are fully applicable to low-LET (linear energy transfer) radioresistant tumor cells/normal tissues such as osteosarcoma cells and chondrocytes, it is believed that radiation-associated damage to DNA does not play a major role in the mechanism of cell death in low-LET radiosensitive tumors/normal tissues such as malignant lymphoma cells and lymphocytes. Hall and Giaccia describe lymphocytes as very radiosensitive, based largely on apoptosis subsequent to irradiation. As described in this review, apoptosis of lymphocytes and lymphoma cells is actually induced by the “hydrogen peroxide (H2O2) effect”, which I propose in this review article for the first time. The mechanism of lymphocyte death via the H2O2 effect represents an ideal model to develop the enhancement method of radiosensitivity for radiation therapy of malignant neoplasms. In terms of imitating the high radiosensitivity of lymphocytes, osteosarcoma cells (representative of low-LET radioresistant cells) might be the ideal model for indicating the conversion of cells from radioresistant to radiosensitive utilizing the H2O2 effect. External beam radiation such as X-rays and high-energy electrons for use in modern radiotherapy are generally produced using a linear accelerator. We theorized that when tumors are irradiated in the presence of H2O2, the activities of anti-oxidative enzymes such as peroxidases and catalase are blocked and oxygen molecules are produced at the same time via the H2O2 effect, resulting in oxidative damage to low-LET radioresistant tumor cells, thereby rendering them highly sensitive to irradiation. In this review, this potential paradigm shift in modern radiation biology/radiation oncology is discussed in detail in terms of overcoming drug/radiation resistance in radiation therapy and/or anti-cancer chemotherapy.

A generalized target theory and its applications.

Different radiobiological models have been proposed to estimate the cell-killing effects, which are very important in radiotherapy and radiation risk assessment. However, most applied models have their own scopes of application. In this work, by generalizing the relationship between “hit” and “survival” in traditional target theory with Yager negation operator in Fuzzy mathematics, we propose a generalized target model of radiation-induced cell inactivation that takes into account both cellular repair effects and indirect effects of radiation. The simulation results of the model and the rethinking of “the number of targets in a cell” and “the number of hits per target” suggest that it is only necessary to investigate the generalized single-hit single-target (GSHST) in the present theoretical frame. Analysis shows that the GSHST model can be reduced to the linear quadratic model and multitarget model in the low-dose and high-dose regions, respectively. The fitting results show that the GSHST model agrees well with the usual experimental observations. In addition, the present model can be used to effectively predict cellular repair capacity, radiosensitivity, target size, especially the biologically effective dose for the treatment planning in clinical applications.

The role of photo- and thermal degradation for CO<sub>2</sub> and CO fluxes in an arid ecosystem

Abstract. Recent studies have suggested the potential importance of abiotic degradation in arid ecosystems. In this study, the role of photo- and thermal degradation in ecosystem CO2 and CO exchange is assessed. A field experiment was performed in Italy using an FTIR-spectrometer (Fourier Transform Infrared) coupled to a flux gradient system and to flux chambers. In a laboratory experiment, field samples were exposed to different temperatures and radiation intensities. No photodegradation-induced CO2 and CO fluxes of in literature suggested magnitudes were found in the field nor in the laboratory study. In the laboratory, we measured CO2 and CO fluxes that were derived from thermal degradation. In the field experiment, CO uptake and emission have been measured and are proposed to be a result of biological uptake and abiotic thermal degradation-production. We suggest that previous studies, addressing direct photodegradation, have overestimated the role of photodegradation and observed fluxes might be due to thermal degradation, which is an indirect effect of radiation. The potential importance of abiotic decomposition in the form of thermal degradation, especially for arid regions, should be considered in future studies.

Astroglial U87 Cells Protect Neuronal SH-SY5Y Cells from Indirect Effect of Radiation by Reducing DNA Damage and Inhibiting Fas Mediated Apoptotic Pathway in Coculture System.

Recent studies provide the evidence that indirect effects of radiation could lead to neuronal cells death but underlying mechanism is not completely understood. On the other hand astroglial cells are known to protect neuronal cells against stress conditions in vivo and invitro. Yet, the fate of neuronal cells and the neuroprotective effect of coculture system (with glial cells) in response to indirect radiation exposure remain rarely discussed. Here, we purpose that the indirect effect of radiation may induce DNA damage by cell cycle arrest and receptor mediated apoptotic cascade which lead to apoptotic death of neuronal SH-SY5Y cells. We also hypothesized that coculture (with glial U87) may relieved the neuronal SH-SY5Y cells from toxicity of indirect effects radiation by reducing DNA damage and expression of apoptotic proteins in vitro. In the present study irradiated cell conditioned medium (ICCM) was used as source of indirect effect of radiation. Neuronal SH-SY5Y cells were exposed to ICCM with and without coculture with (glial U87) in transwell coculture system respectively. Various endpoints such as, cell survival number assay, Annexin V/PI assay, cell cycle analysis by flow cytometer, mRNA level of Fas receptor by q RT-PCR, expression of key apoptotic proteins by western blot and estimation of neurotrophic factors by ELISA method were analyzed into neuronal SH-SY5Y cells with and without co culture after ICCM exposure respectively. We found that ICCM induced DNA damage in neuronal SH-SY5Y cells by significant increase in cell cycle arrest at S-phase (***P < 0.001) which was further supported by over expression of P53 protein (**P < 0.01). While coculture (with glial U87), significantly reduced the ICCM induced cell cycle arrest and expression of P53 ((###) P < 0.001) neuronal SH-SY5Y cells. Further investigation of the underlying apoptotic mechanism revealed that in coculture system; ICCM induced elevated level of FAS mRNA level was significantly reduced ((###) P < 0.001) in neuronal SH-SY5Y cells which was followed by significant reduction in expression of key apoptotic protein i.e., FADD ((###) P < 0.001), caspase-8 ((###) P < 0.001), and cleaved caspase-3 ((###) P < 0.001) as compare to neuronal SH-SY5Y cells which received ICCM without coculture. Intriguingly, concentration of neurotrophic factors such as, GDNF and BDNF were significantly increased ((###) P < 0.001) in neuronal SH-SY5Y after coculture (with glial U87) cells. Hence, these findings infer that the receptor mediated pathway could be the one way through which indirect effects of radiation cause neurotoxicity. However, in co-cultures system (with glial U87) neuronal SH-SY5Y depicts remarkable resistance against ICCM induced neurotoxicity.

Proton-induced direct and indirect damage of plasmid DNA.

Clustered DNA damage induced by 10, 20 and 30MeV protons in pBR322 plasmid DNA was investigated. Besides determination of strand breaks, additional lesions were detected using base excision repair enzymes. The plasmid was irradiated in dry form, where indirect radiation effects were almost fully suppressed, and in water solution containing only minimal residual radical scavenger. Simultaneous irradiation of the plasmid DNA in the dry form and in the solution demonstrated the contribution of the indirect effect as prevalent. The damage composition slightly differed when comparing the results for liquid and dry samples. The obtained data were also subjected to analysis concerning different methodological approaches, particularly the influence of irradiation geometry, models used for calculation of strand break yields and interpretation of the strand breaks detected with the enzymes. It was shown that these parameters strongly affect the results.

Glial U87 cells protect neuronal SH-SY5Y cells from indirect effect of radiation by reducing oxidative stress and apoptosis.

Recent studies have demonstrated the role of indirect effect of radiation in neurodegeneration. However, the role of glial cells in neuroprotection against indirect effect of radiation is still not clear, although they are known to protect neurons under stress conditions in central nervous system. Our study showed that indirect effect of radiation increased the oxidative stress that further enhances the expression of key apoptotic proteins and leads to neuronal cell death. We also investigated the indirect effect of radiation on neuronal cells in the presence of glial cells in a transwell co-culture system, while our analysis was focused on neuronal cells. Irradiated cell-conditioned medium (ICCM) was used as source of indirect radiation and neuroprotective effect was analyzed by various endpoints. It was observed that ICCM-induced reactive oxidative species level was significantly reduced in SH-SY5Y cells co-cultured with glial U87 cells, which might help to maintain the integrity of mitochondrial membrane potential. Increased levels of antioxidant enzyme superoxide dismutase and antioxidant glutathione were observed in SH-SY5Y cells co-cultured with glial U87 cells. Moreover, it was also observed that co-culture with glial cells inhibits the expression of ICCM-induced apoptotic proteins, i.e. Bax, cytochrome c, and caspase-3 in SH-SY5Y cells. Hence, it can be speculated that in co-culture system glial cells may protect the neuronal SH-SY5Y cells by reducing the ICCM-induced oxidative stress and apoptotic death.

Indirect effects of radiation induce apoptosis and neuroinflammation in neuronal SH-SY5Y cells.

Recent studies have evaluated the role of direct radiation exposure in neurodegenerative disorders; however, association among indirect effects of radiation and neurodegenerative diseases remains rarely discussed. The objective of this study was to estimate the relative risk ofneurodegeneration due to direct and indirect effects of radiation. (60)Co gamma ray was used as source of direct radiation whereas irradiated cell conditioned medium (ICCM) was used to mimic the indirect effect of radiation. To determine the potency of ICCM to inhibit neuronal cells survival colony forming assay was performed. The role of ICCM to induce apoptosis in neuronal SH-SY5Y cells was estimated by TUNEL assay and Annexin V/PI assay. Level of oxidative stress and the concentration of inflammatory cytokines after exposing to direct radiation and ICCM were evaluated by ELISA method. Expression of key apoptotic protein following direct and indirect radiation exposure was investigated by western blot technique. Experimental data manifest that ICCM account loss of cell survival and increase apoptotic induction in neuronal SH-SY5Y cells that was dependent on time and dose. Moreover, ICCM stimulate significant release of inflammatory cytokines i.e., tumor necrosis factor TNF-alpha (P<0.01), Interleukin-1 (IL-1, P<0.001), and Interleukin-6 (IL-6, P<0.001) in neuronal SH-SY5Y cells and elevate the level of oxidative stress (MDA, P<0.01). Up-regulation of key apoptotic protein expression i.e., Bax, Bid, cytochrome C, caspase-8 and caspase-3 confirms the toxicity of ICCM to neuronal cells. This study provides the evidence that indirect effect of radiation can be as much damaging to neuronal cells as direct radiation exposure can be. Hence, more focused research on estimation risks of indirect effect of radiation to CNS at molecular level may help to reduce the uncertainty about cure and cause of several neurodegenerative disorders.

The role of UV-B radiation and precipitation on straw decomposition and topsoil C turnover

In arid and semi-arid area, ultraviolet-B (UV-B) radiation plays a mainly positive role in litter decomposition. In subtropical area, however, the role of UV-B radiation remains uncertain due to the interference of precipitation. To evaluate the potential contribution of precipitation to the role of UV-B radiation, we exposed 84 bags of rice straw to ambient and reduced UV-B radiation, with and without water addition after each precipitation event, on the roof of a building at Huazhong Agricultural University (Wuhan, China). Additionally, the indirect effects of UV-B radiation on soil dissolved organic carbon (DOC) were investigated by placing 70-g soil samples beneath 5-g straw bags with precipitation treatments. Mass loss, DOC and water extractable phenols (WEP) were monitored over 228 days. Subsequently, microbial facilitation was studied, by incubating straw and soil samples exposed for the longest period (228 days) in the laboratory at 25 °C, and by afterwards analyzing their CO2–C emission. Our results demonstrated that UV-B radiation did not significantly affect straw mass loss, but induced an increase in straw DOC, WEP and CO2–C emission by 20.6%, 10.7% and 20.4%, respectively, under dry conditions. Whereas, combined with precipitation, the effects of UV-B radiation on straw DOC, WEP and CO2–C emission were negligible. Only a small decrease in soil DOC (9.9%) and CO2–C (4.0%) was observed. Furthermore, UV-B radiation interacted significantly with precipitation during straw decomposition. These results indicate that for dry conditions UV-B radiation accelerates straw decomposition by increasing DOC content. For wet conditions, however, the effects of UV-B radiation on straw decomposition are balanced out and even negative on topsoil C turnover.

Modeling Clinical Radiation Responses in the IMRT Era

The purpose of this review is to highlight the critical issues of radiobiological models, particularly as they apply to clinical radiation therapy. Developing models of radiation responses has a long history that continues to the present time. Many different models have been proposed, but in the field of radiation oncology, the linear-quadratic (LQ) model has had the most impact on the design of treatment protocols. Questions have been raised as to the value of the LQ model given that the biological assumption underlying it has been challenged by molecular analyses of cell and tissue responses to radiation. There are also questions as to use of the LQ model for hypofractionation, especially for high dose treatments using a single fraction. While the LQ model might over-estimate the effects of large radiation dose fractions, there is insufficient information to fully justify the adoption of alternative models. However, there is increasing evidence in the literature that non-targeted and other indirect effects of radiation sometimes produce substantial deviations from LQ-like dose-response curves. As preclinical and clinical hypofractionation studies accumulate, new or refined dose-response models that incorporate high-dose/fraction non-targeted and indirect effects may be required, but for now the LQ model remains a simple, useful tool to guide the design of treatment protocols.

Effects of different doses of gamma irradiation on oxygen and water vapour transmission rate of preserved human amniotic membrane

Preserved human amniotic membrane either air dried or glycerol preserved has been used effectively to treat superficial and partial thickness wounds without leaving any obvious hypertrophic scar. The preserved amnion, sterilised by ionising radiation, is known as an effective barrier for heat, fluid and protein loss while adheres nicely on wound. Air drying slightly reduced the oxygen transmission rate (OTR) of the amnion and the value significantly dropped after 15 kGy (p < 0.05). Glycerol preservation significantly reduced (p < 0.05) the OTR indicating less oxygen transmitted through the well structured cells of the amnion. Increase in the OTR with the increasing radiation doses up to 35 kGy possibly due to direct effects of radiation that resulted in large intercellular gaps. Both preservation methods significantly increased (p < 0.05) the water vapour transmission rate (WVTR). However, the low WVTR in the air dried amnion at 15 and 25 kGy was postulated due to cross-linking of collagen. Changes in the biophysical properties can be linked to direct and indirect effects of radiation on collagen bundles. The radiation dose of 25 kGy caused no adverse effect on biophysical properties hence it is still acceptable to sterilize both the air dried and the glycerol preserved amnions.

Impact of increasing Ultraviolet-B (UV-B) radiation on photosynthetic processes

Increased UV-B radiation on the earth’s surface due to depletion of stratospheric ozone layer is one of the changes of current climate-change pattern. The deleterious effects of UV-B radiation on photosynthesis and photosynthetic productivity of plants are reviewed. Perusal of relevant literature reveals that UV-B radiation inflicts damage to the photosynthetic apparatus of green plants at multiple sites. The sites of damage include oxygen evolving complex, D1/D2 reaction center proteins and other components on the donor and acceptor sides of PS II. The radiation inactivates light harvesting complex II and alters gene expression for synthesis of PS II reaction center proteins. Mn cluster of water oxidation complex is the most important primary target of UV-B stress whereas D1 and D2 proteins, quinone molecules and cytochrome b are the subsequent targets of UV-B. In addition, photosynthetic carbon reduction is also sensitive to UV-B radiation which has a direct effect on the activity and content of Rubisco. Some indirect effects of UV-B radiation include changes in photosynthetic pigments, stomatal conductance and leaf and canopy morphology. The failure of protective mechanisms makes PS II further vulnerable to the UV-B radiation. Reactive oxygen species are involved in UV-B induced responses in plants, both as signaling and damaging agents. Exclusion of ambient UV components under field conditions results in the enhancement of the rate of photosynthesis, PS II efficiency and subsequently increases the biomass accumulation and crop yield. It is concluded that predicted future increase in UV-B irradiation will have significant impact on the photosynthetic efficiency and the productivity of higher plants.

Biologically Weighted Quantities in Radiotherapy: an EMRP Joint Research Project

Funded within the European Metrology Research Programme (EMRP) [1], the joint research project “Biologically weighted quantities in radiotherapy” (BioQuaRT) [2] aims to develop measurement and simulation techniques for determining the physical properties of ionising particle tracks on different length scales (about 2 nm to 10 μm), and to investigate the correlation of these track structure characteristics with the biological effects of radiation at the cellular level. Work package 1 develops micro-calorimeter prototypes for the direct measurement of lineal energy and will characterise their response for different ion beams by experiment and modelling. Work package 2 develops techniques to measure particle track structure on different length scales in the nanometre range as well as a measurement device integrating a silicon microdosimeter and a nanodosimeter. Work package 3 investigates the indirect effects of radiation based on probes for quantifying particular radical and reactive oxygen species (ROS). Work package 4 focuses on the biological aspects of radiation damage and will produce data on initial DNA damage and late effects for radiotherapy beams of different qualities. Work package 5 provides evaluated data sets of DNA cross-sections and develops a multi-scale model to address microscopic and nanometric track structure properties. The project consortium includes three linked researchers holding so-called Researcher Excellence Grants, who carry out ancillary investigations such as developing and benchmarking a new biophysical model for induction of early radiation damage and developing methods for the translation of quantities derived from particle track structure to clinical applications in ion beam therapy.

Radiofrequency에 노출된 Chlamydomonas sp.의 mycosporine-like amino acids 생합성 유전자 발현

Mycosporine-like amino acids (MAAs) are UV-absorbing substances, and diverse marine organisms have the evolved the capacity to diminished the direct and indirect damaging effects of environmental ultraviolet radiation by synthesis and accumulation of MAAs. In this study, we manufactured a radiofrequency (RF) generation device and applied to microalgal culture. 0.35±0.05 mHz of RF was supplied to culture vessel for Chlamydomonas sp. and samples were harvested at the designated time intervals (1, 0.5, 1 and 2 hr). MAAs biosynthetic genes, dehydroquinate synthase homolog (DHQS-like) and nonribosomal peptide synthetase homolog (NRPS-like), were cloned from Chlamydomonas sp. and their gene expressions under the RF exposure were analyzed using qRT-PCR. DHQS-like and NRPS-like gene expressions of Chlamydomonas sp. exposed to RF were increased 1.46 and 1.19 fold at 1 hr, respectively. These results means that DHQS-like and NRPS-like genes can be good biomarker candidates for diagnosis of MAAs biosynthesis in the Chlamydomonas sp.

DNA double strand breaks induced by the indirect effect of radiation are more efficiently repaired by non-homologous end joining compared to homologous recombination repair

The aim of this study was to investigate the relative involvement of three major DNA repair pathways, i.e., non-homologous end joining (NHEJ), homologous recombination (HRR) and base excision (BER) in repair of DNA lesions of different complexity induced by low- or high-LET radiation with emphasis on the contribution of the indirect effect of radiation for these radiation qualities.A panel of DNA repair-deficient CHO cell lines was irradiated by 137Cs γ-rays or radon progeny α-particles. Irradiation was also performed in the presence of 2M DMSO to reduce the indirect effect of radiation and the complexity of the DNA damage formed. Clonogenic survival and micronucleus assays were used to estimate efficiencies of the different repair pathways for DNA damages produced by direct and indirect effects.Removal of the indirect effect of low-LET radiation by DMSO increased clonogenic survival and decreased MN formation for all cell lines investigated. A direct contribution of the indirect effect of radiation to DNA base damage was suggested by the significant protection by DMSO seen for the BER deficient cell line. Lesions formed by the indirect effect are more readily repaired by the NHEJ pathway than by HRR after irradiation with γ-rays or α-particles as evaluated by cell survival and the yields of MN.The results obtained with BER- and NHEJ-deficient cells suggest that the indirect effect of radiation contributes significantly to the formation of repair substrates for these pathways.

Innate Immune Genes Including a Mucin-Like Gene,mul-1, Induced by Ionizing Radiation inCaenorhabditis elegans

The effect of radiation on the intestine has been studied for more than one hundred years. It remains unclear, however, whether this organ uses specific defensive mechanisms against ionizing radiation. The infection with Pseudomonas aeruginosa (PA14) in Caenorhabditis elegans induces up-regulation of innate immune response genes. Here, we found that exposure to ionizing radiation also induces certain innate immune response genes such as F49F1.6 (termed mul-1), clec-4, clec-67, lys-1 and lys-2 in the intestine. Moreover, pre-treatment with ionizing radiation before seeding on PA14 lawn plate significantly increased survival rate in the nematode. We also studied transcription pathway of the mul-1 in response to ionizing radiation. Induction of mul-1 gene was highly dependent on the ELT-2 transcription factor and p38 MAPK. Moreover, the insulin/IGF-1 signal pathway works to enhance induction of this gene. The mul-1 gene showed a different induction pattern from the DNA damage response gene, ced-13, which implies that the expression of this gene might be triggered as an indirect effect of radiation. Silencing of the mul-1 gene led to growth retardation after treatment with ionizing radiation. We describe the cross-tolerance between the response to radiation exposure and the innate immune system.