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1.
Int J Radiat Oncol Biol Phys ; 106(2): 440-448, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31928642

RESUMO

PURPOSE: Recent studies suggest that ultrahigh-dose-rate, "FLASH," electron radiation therapy (RT) decreases normal tissue damage while maintaining tumor response compared with conventional dose rate RT. Here, we describe a novel RT apparatus that delivers FLASH proton RT (PRT) using double scattered protons with computed tomography guidance and provide the first report of proton FLASH RT-mediated normal tissue radioprotection. METHODS AND MATERIALS: Absolute dose was measured at multiple depths in solid water and validated against an absolute integral charge measurement using a Faraday cup. Real-time dose rate was obtained using a NaI detector to measure prompt gamma rays. The effect of FLASH versus standard dose rate PRT on tumors and normal tissues was measured using pancreatic flank tumors (MH641905) derived from the KPC autochthonous PanCa model in syngeneic C57BL/6J mice with analysis of fibrosis and stem cell repopulation in small intestine after abdominal irradiation. RESULTS: The double scattering and collimation apparatus was dosimetrically validated with dose rates of 78 ± 9 Gy per second and 0.9 ± 0.08 Gy per second for the FLASH and standard PRT. Whole abdominal FLASH PRT at 15 Gy significantly reduced the loss of proliferating cells in intestinal crypts compared with standard PRT. Studies with local intestinal irradiation at 18 Gy revealed a reduction to near baseline levels of intestinal fibrosis for FLASH-PRT compared with standard PRT. Despite this difference, FLASH-PRT did not demonstrate tumor radioprotection in MH641905 pancreatic cancer flank tumors after 12 or 18 Gy irradiation. CONCLUSIONS: We have designed and dosimetrically validated a FLASH-PRT system with accurate control of beam flux on a millisecond time scale and online monitoring of the integral and dose delivery time structure. Using this system, we found that FLASH-PRT decreases acute cell loss and late fibrosis after whole-abdomen and focal intestinal RT, whereas tumor growth inhibition is preserved between the 2 modalities.


Assuntos
Órgãos em Risco/efeitos da radiação , Terapia com Prótons/instrumentação , Lesões Experimentais por Radiação/prevenção & controle , Proteção Radiológica/instrumentação , Radioterapia Guiada por Imagem/instrumentação , Abdome/efeitos da radiação , Animais , Proliferação de Células/efeitos da radiação , Desenho de Equipamento/métodos , Estudos de Viabilidade , Feminino , Fibrose , Raios gama , Intestino Delgado/patologia , Intestino Delgado/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Tratamentos com Preservação do Órgão/instrumentação , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco/patologia , Neoplasias Pancreáticas/radioterapia , Terapia com Prótons/métodos , Proteção Radiológica/métodos , Radiometria/métodos , Radioterapia Guiada por Imagem/métodos , Espalhamento de Radiação , Células-Tronco/efeitos da radiação , Tomografia Computadorizada por Raios X
2.
Int J Radiat Biol ; 96(1): 100-111, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-29447591

RESUMO

Purpose: Characterization of a novel partial-body irradiation (PBI) shielding strategy in nonhuman primates (NHP; rhesus macaques), aimed at protecting the oral cavity, with respect to various gastrointestinal acute radiation syndrome (GI-ARS) syndrome parameters as well as buccal ulceration development.Materials and methods: NHPs were irradiated using a Cobalt-60 gamma source, in a single uniform dose, ranging from 9-13 Gy and delivered at 0.60-0.80 Gy min-1. Animals were either partially shielded via oral cavity shielding (PBIOS) or underwent total-body irradiation (TBI).Results: Clinical manifestations of GI-ARS, and also radiation-induced hematology and clinical chemistry changes, following PBIOS were comparable to the PBI NHP GI-ARS model utilizing shielding of the distal pelvic limbs and were significantly milder than TBI at similar radiation doses. Nadir citrulline levels were comparable between PBIOS and TBI but signs of recovery appeared earlier in PBIOS-treated animals. The PBIOS model prevented oral mucositis, whereas the TBI model presented buccal ulcerations at all tested radiation dose levels.Conclusions: Taken together, these results suggest that the PBIOS model is a suitable alternative to traditional PBI. For GI-ARS investigations requiring orally administered medical countermeasures, PBIOS confers added value due to the prevention of oral mucositis over traditional PBI.


Assuntos
Boca/efeitos da radiação , Proteção Radiológica/métodos , Síndrome Aguda da Radiação/sangue , Síndrome Aguda da Radiação/etiologia , Síndrome Aguda da Radiação/patologia , Animais , Citrulina/sangue , Radioisótopos de Cobalto/efeitos adversos , Raios gama/efeitos adversos , Macaca mulatta , Masculino , Análise de Sobrevida , Úlcera/sangue , Úlcera/etiologia , Úlcera/patologia
3.
Sci Total Environ ; 702: 135076, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31734608

RESUMO

Rapid and reliable ionization radiation (IR) exposure estimation has become increasingly important in environment due to the urgent requirement of medical evaluation and treatment in the event of nuclear accident emergency. Human DNA repair genes can be identified as important candidate biomarkers to assess IR exposure, while how to find the enough sensitive and specific biomarkers in the DNA repair networks is still challenged and not fully determined. The conserved features of DNA repair pathways may facilitate interdisciplinary studies that cross the traditional boundaries between animal and plant biology, with the aim of identifying undiscovered human DNA repair genes for potential radiation-responsive biomarkers. In this work, an in silico method of homologous comparison was performed to identify the human orthologues of A. thaliana DNA repair genes, and thereby to explore the sensitive and specific human radiation-responsive genes to evaluate the IR exposure levels. The results showed that a total of 16 putative candidate genes were involved in the human DNA repair pathways of homologous recombination (HR) and non-homologous end joining (NHEJ), and most of them were confirmed by previous experiments. Additionally, we analyzed the gene expression patterns of these 16 candidate genes in several human transcript microarray datasets with different IR treatments. The results indicated that most of the gene expression levels for these candidate genes were significantly changed under different radiation treatments. Based on these results, we integrated these putative human DNA repair genes into the DNA repair pathways to propose new insights of the HR and NHEJ pathways, which can also provide the potential targets for the development of radiation biomarkers. Notably, two putative DNA repair genes, named ERCC1 and ESCO2, were identified and were considered to be the sensitive and specific biomarkers in response to γ-ray exposures.


Assuntos
Arabidopsis/fisiologia , Biodegradação Ambiental , Biomarcadores/metabolismo , Raios gama , Reparo do DNA por Junção de Extremidades , Reparo do DNA , Humanos
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 2030-2034, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839079

RESUMO

Abstract  With the development of transfusion medicine and the mastery of blood transfusion diagnosis and treatment techniques, the application of irradiated blood products in our country is gradually increasing. In recent years, the proportion of blood transfused by γ-rays has been increasing. In some foreign countries, the application rate of blood irradiated by radiotherapy is as high as 95%. At present, it is still in the promotion stage in China. This article summarizes the commonly used methods of blood irradiation, including the choice of irradiation source, the core dose and common irradiation targets, compares the difference of different irradiation methods, and generalizes the common application of blood irradiation. It is proposed that in addition to TA-GVHD application, blood irradiation may have a broad prospects for cancer therapy and microbial killing.


Assuntos
Doença Enxerto-Hospedeiro , Transfusão de Sangue , China , Raios gama , Humanos
5.
J Food Sci ; 84(11): 3179-3185, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31589337

RESUMO

The present work studied, for the first time, the effect of two technologies on the hydration and germination process of beans: ionizing irradiation and ultrasound. In addition, this work proposed a possible biological effect of ultrasound to describe its effect on grain hydration. Carioca beans were irradiated at doses of 2.3 and 3.8 kGy using γ-rays, establishing different metabolic activities for the beans. Then, they were hydrated with and without the ultrasound technology (91 W/L and 25 kHz) at 25 °C. Both the hydration and germination kinetics were evaluated considering the application of both technologies alone and in combination. As results, irradiation did not significantly affect (P > 0.05) the hydration rate, the equilibrium moisture, or the lag phase time, but ultrasound affected them, reducing 50% of the processing time. On the other hand, only the equilibrium moisture was slightly reduced by the interactive effect of irradiation and ultrasound technology, which was discussed based on different metabolism levels. Furthermore, the germination process of carioca bean was hindered by both the studied variables, reducing its germination capacity to 0% in some cases. Therefore, by studying the effect of ultrasound on beans with different active metabolism (due to different irradiation doses), it was suggested that both physical and biological mechanisms are involved during hydration process and that both can be affected by ultrasound. Further, irradiation could be used on carioca beans with objectives such as avoid germination, insects, and microorganism's growth, without an important effect on the hydration kinetics. PRACTICAL APPLICATION: Ultrasound technology has demonstrated to accelerate the soaking process of several legume grains. However, sometimes, grains are irradiated for disinfestation purpose to improve their shelf life. Indeed, irradiation can change the grain properties as the cooking time, hydration time, and germination capacity. Therefore, this work verified if irradiation changes the desirable effect of ultrasound on grain processing: soaking and germination. Moreover, this work novelty is also based on describing the phenomena: by proposing a possible biological effect, further approaches to improve the grain processing can be achieved.


Assuntos
Germinação/efeitos da radiação , Phaseolus/efeitos da radiação , Sementes/crescimento & desenvolvimento , Culinária , Raios gama , Temperatura Alta , Cinética , Phaseolus/química , Phaseolus/crescimento & desenvolvimento , Phaseolus/metabolismo , Sementes/química , Sementes/metabolismo , Sementes/efeitos da radiação , Ultrassom , Água/análise , Água/metabolismo
6.
Int J Syst Evol Microbiol ; 69(12): 3696-3701, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31647398

RESUMO

A Gram-stain-negative, non-motile, strictly aerobic, coccus-shaped bacterium, designated S14-83T, was isolated from a soil sample collected from the South Shetland Islands of Antarctica. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain is a novel member of the genus Deinococcus, with Deinococcus alpinitundrae as its closest relative (96.1 % similarity). The DNA G+C content of the strain was 61.1 mol% and the major respiratory quinone was MK-8. Major cellular fatty acids were summed feature 3 (C16 : 1ω7c/C16 : 1ω6c) and C16 : 0. As well as containing glycophospholipid, aminophospholipids and glycolipid as major polar lipids, there were also some unknown polar lipids. The diagnostic diamino acid in the cell-wall peptidoglycan was ornithine, corroborating the assignment of the strain to the genus Deinococcus. Strain S14-83T was shown to be extremely resistant to gamma radiation (>10 kGy) and UV light (460 Jm-2). On the basis of phylogenetic, chemotaxonomic and phenotypic data presented here, strain S14-83T represents a novel species of the genus Deinococcus, for which the name Deinococcus psychrotolerans sp. nov. is proposed. The type strain is S14-83T (=CCTCC AB 2015449T= DSM 105285 T).


Assuntos
Deinococcus/classificação , Filogenia , Microbiologia do Solo , Regiões Antárticas , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Deinococcus/isolamento & purificação , Deinococcus/efeitos da radiação , Ácidos Graxos/química , Raios gama , Glicolipídeos/química , Peptidoglicano/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Raios Ultravioleta , Vitamina K 2/análogos & derivados , Vitamina K 2/química
7.
Life Sci ; 238: 116981, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31639394

RESUMO

AIM: Endothelial cell damage is critical to understand since its presence in the entire body makes the damage widespread instead of being localized. Being a major component of stem cell niche in bone marrow, deems it essential to gain knowledge of the damage to endothelium associated with bone marrow. Since radiation exposure has become common to numerous therapeutic modalities, its effects on bone marrow and its endothelial cells are crucial to understand. MATERIAL & METHODS: Microarray analysis was performed on irradiated human bone marrow endothelial cells (hBMECs) with and without prior treatment with radioprotectant amifostine to assess the effects of radiation on signalling pathways and the subsequent changes in pathways when treated with radioprotectant prior to radiation exposure. KEY FINDINGS: It was seen that adhesion pathways that were usually inactivated under normal circumstances were stimulated post radiation. However, where in the case of radiation exposure, these adhesion pathways included leukocyte adhesion and migration; in the case of radioprotected conditions the pathways revolve around cell-substrate adhesion and cell spreading. Genes like ROCK1, FLNA, RAC1, PRKCZ and MAP3K8 were seen to regulate the molecular switch between leukocyte-cell adhesion to cell-substrate adhesion. SIGNIFICANCE: Our study demonstrated that irradiated endothelium supports leukocyte adhesion and migration but shifts to substrate adhesion dependent cell spreading under radioprotected conditions in order to repair the monolayer damage from the radiation. The genes responsible for the shift were identified and can be employed to manipulate cell adhesion characteristics for the treatment of diseases caused by radiation or inflammation.


Assuntos
Amifostina/farmacologia , Biomarcadores/metabolismo , Medula Óssea/metabolismo , Adesão Celular , Endotélio Vascular/metabolismo , Raios gama , Leucócitos/metabolismo , Medula Óssea/efeitos dos fármacos , Medula Óssea/efeitos da radiação , Células Cultivadas , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/efeitos da radiação , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Redes Reguladoras de Genes/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos da radiação , Humanos , Leucócitos/efeitos dos fármacos , Leucócitos/efeitos da radiação , Protetores contra Radiação/farmacologia
8.
Phys Med ; 64: 33-39, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31515033

RESUMO

Proton radiotherapy has a potential to provide an effective cancer treatment while sparing greater volume of healthy tissue than the conventional X-ray based radiotherapy. However, in lungs this potential is hindered by motion due to breathing. An important quantity in treatment verification is the correlation between the respiratory phases (RP) and the timing of pencil beam scanning (PBS). In this note, we demonstrate how the RP can be estimated using Prompt gamma (PG) detection profiles collected during a treatment. We utilized a 4D-CT of a patient with lung cancer, a treatment plan and a PG simulator. The treatment plan consisted of ten layers corresponding to ten proton energies. The RPs of the 4D-CT were interpolated using a deformable registration algorithm, so as to have fifty RPs in total. Deviations from regular breathing were introduced via time dependent frequency modulation. Fifty unique breathing patterns were generated, for which PG profiles were simulated for each pencil beam. Poisson noise was added to each PG profile to account for photon statistics. The RPs were estimated by comparing the PG profiles with and without Poisson noise via three different methods: the RP associated with each layer was estimated 1) independently of the other layers, 2) using a linear correlation between the layers, and 3) using a quadratic correlation between the layers. The best model, the quadratic model, yielded an average error in RP estimation relative to the breathing period of 5% of the breathing period or less with a 90% confidence interval.


Assuntos
Tomografia Computadorizada Quadridimensional , Raios gama , Terapia com Prótons/métodos , Respiração , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/radioterapia , Método de Monte Carlo , Planejamento da Radioterapia Assistida por Computador , Fatores de Tempo
9.
Int J Radiat Biol ; 95(11): 1543-1546, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31550183

RESUMO

Introduction: In multi-well cell culture plates, wells are bordered by air cavities. The air cavity inhomogeneities can reduce the amount of delivered dose. In this study, the effect of these cavities on cell survival was investigated.Materials and methods: A special phantom was designed to house the plates and air cavities were filled by water equivalent materials. Cultured melanoma cells were irradiated using 6MV photon for 200 cGy. MTT and clonogenic assay tests were used to evaluate cell survival.Results: Results of MTT assay showed mean survival percentage for irradiated cells in the first group, i.e. plates with air cavities, was 18.9% higher than the second group with air cavities filled with paraffin. Clonogenic assay results showed a maximum of 37% difference in the mean of number of colonies between the first group and the second group (p value < .05).Conclusions: The presence of air cavities in multi-well cell culture plates reduced radiation cell kill by up to 37%. To ensure the accuracy of delivered dose, it is necessary to replace the air cavities as well as the air surrounding the plates by a water equivalent material.


Assuntos
Ar , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos da radiação , Melanoma/radioterapia , Neoplasias Cutâneas/radioterapia , Bioensaio , Linhagem Celular , Simulação por Computador , Raios gama , Humanos , Método de Monte Carlo , Imagens de Fantasmas , Fótons , Polimetil Metacrilato , Radiobiologia , Água
10.
Mol Immunol ; 114: 578-590, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31526941

RESUMO

Immune system is a critical modulator of radiation-induced biological effects. In this study, we have assessed protective potential of N-acetyl tryptophan glucoside (NATG) pre-treatment in bone marrow of gamma radiation challenged mice. Isolated bone marrow cells were analysed for cell cycle progression by flow cytometry, while various pro-/anti-inflammatory cytokine profiles were performed by ELISA method. Overall radioprotective ability of NATG in ensuring protection against gamma radiation-induced damage was assessed by evaluating whole body survival analysis and haematological studies on 9 Gy irradiated mice with/without NATG pre-treatment. Results exhibited pre-treatment with 150 mg/kg b.wt oral administration of NATG as most effective against 9 Gy radiation exposure. Moreover, NATG showed non-interfering effect on cell cycle progression in pre-treated irradiated mice group when compared to radiation alone group. In addition, cytokine expression analysis indicated significant (p > 0.05) elevation in levels of IFN-γ, IL-2, IL-12, IL-13 and IL-17 in NATG pre-treated irradiated mice in comparison to radiation alone group. On the contrary, NATG pre-treatment was observed to alleviate levels of TNF-α and IL-10 significantly (p < 0.05) in radiated group as compared to only irradiated mice group. Furthermore, NATG pre-treatment to 9 Gy radiation exposed mice aided in restoring their haematological parameters in terms of haemoglobin counts, RBC counts, WBC counts, hematocrit levels, platelets and granulocyte levels in comparison to irradiated alone mice, thus enhancing their immune system and contributing towards a better survival against gamma radiation-induced deleterious effects. Conclusively, this study highlights the potential of NATG as a prospective radiation countermeasure agent against ionizing radiation-induced assaults to the immune system.


Assuntos
Raios gama/efeitos adversos , Imunossupressão/efeitos adversos , Substâncias Protetoras/farmacologia , Animais , Apoptose/efeitos dos fármacos , Citocinas/metabolismo , Interleucina-10/metabolismo , Interleucina-13/metabolismo , Interleucina-17/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Triptofano/análogos & derivados , Triptofano/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
11.
Mol Immunol ; 114: 561-570, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31522074

RESUMO

Autism is a neurodevelopmental disorder characterized by deficits and qualitative impairments in communication and implicit skill learning. Its prevalence is higher than previous estimates, and treatments have limited efficacy and are costly. Here, we assessed the therapeutic potential of JNJ77777120 (JNJ), a histamine-4 receptor (H4R) antagonist, using BTBR T+ Itpr3tf/J (BTBR) mice, a confirmed model of autism, and C57BL/6J (C57) mice, a commonly chosen reference strain. We first examined the effects of JNJ treatment on BTBR mice exposed to gamma-rays (irradiation-exposed) using a three-chambered apparatus. We further investigated the possible molecular mechanisms through which JNJ administration modulates IL-17A-, RORγT-, IL-22-, T-bet-, STAT3-, ICOS-, and Foxp3-producing CD8+ T cells in the spleens of irradiation-exposed BTBR mice. The effects of JNJ administration on the mRNA and protein expression of IL-17A, RORγT, IL-22, T-bet, STAT-3, pSTAT3, IL-10, and Foxp3 in brain tissue were also explored. Results showed that JNJ treatment with irradiation exposure increased social interactions in BTBR mice compared to that in irradiation-exposed BTBR mice. Additionally, JNJ-treated and irradiation-exposed BTBR mice exhibited decreases in IL-17A-, RORγT-, IL-22-, T-bet-, and STAT3-producing CD8+ T cells and increases in ICOS- and Foxp3-producing CD8+ T cells. Moreover, JNJ treatment and irradiation exposure in BTBR mice regulated the mRNA and protein expression levels of IL-17A, RORγT, IL-22, T-bet, STAT3, pSTAT-3, IL-10, and Foxp3 in the brain tissue. These results suggest that JNJ is useful for the treatment of autism, as this H4R antagonist could block inflammatory cytokine production and transcription factor signaling.


Assuntos
Linfócitos T CD8-Positivos/efeitos dos fármacos , Indóis/farmacologia , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/antagonistas & inibidores , Piperazinas/farmacologia , Receptores Histamínicos H4/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Proteínas com Domínio T/antagonistas & inibidores , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Modelos Animais de Doenças , Raios gama/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Proteínas/metabolismo
12.
Int J Radiat Biol ; 95(12): 1744-1751, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31486707

RESUMO

Purpose: Inflorescence architecture is an important trait in the seed production of grain legumes. As several genes are responsible for this trait, any mutation, on these genes, may cause change in the inflorescence architecture. This study was conducted to evaluate inflorescence architecture in faba bean exposed to gamma radiation and to characterize the inflorescence architecture mutants phenotypically.Materials and methods: Faba bean M2 seeds (4898) generated from M1 generation of cultivars Hassawi 2 and ILB4347 were used in this study. M1 seeds were produced by irradiation treatments at two doses of gamma radiations (25 and 50 Gy). Faba bean M2 seeds were planted under field conditions. A total of 4032 mutant plants out of 4898 M2 seeds were evaluated for their inflorescence architecture.Results: A total of 20 determinate mutants were found and classified into four different types. Determinate type 1 was characterized by the formation of single terminal inflorescence on shoot apical meristem (SAM), type 2 by the formation of multiple inflorescences on SEM and generated upper branches that act as indeterminate type. Type 3 was characterized by the formation of a panicle-like inflorescence. While type 4 was characterized by the formation of primary and secondary panicle-like inflorescence. All of the determinate mutant types had shorter plant height and earlier maturity than control indeterminate type but had lower biological yield and seed yield. Among the determinate mutant types, determinate type 1 was only mutant that had a higher harvest index than the control indeterminate type. This promising mutant can be used to further breeding program to increase biological yield and seed yield.Conclusions: This study indicated potential of gamma radiation in inducing novel inflorescence architecture in faba bean. The mutants developed are valuable resources to study genes related to inflorescence architecture through forward genetics approach.


Assuntos
Raios gama , Inflorescência/anatomia & histologia , Inflorescência/efeitos da radiação , Mutação , Vicia faba/genética , Vicia faba/efeitos da radiação , Fenótipo , Vicia faba/anatomia & histologia
13.
J Environ Radioact ; 208-209: 106038, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31494388

RESUMO

Aerial Gamma-Ray Surveys (GRS) are ideal for tracking anthropogenic gamma radiation releases and transport. The interpretation of a GRS can be complicated by natural gamma-ray sources such as atmospheric radon, cosmic rays, geologic materials, and even the survey equipment itself. Some of these complicating factors can be accounted for or corrected by calibration or mathematic techniques. Real-time algorithms that attempt to enhance potential radiogenic anomalies over background are also in use. However, natural geology is a source of significant background gamma-ray production and neither mathematical corrections nor real-time algorithmic approaches directly account for geology and geochemistry. In this study, we advance techniques to predict geologic background exposure rates using rapid and practical methods which can be achieved in the field. In addition we generate models that focus specifically on highlighting radiogenic anomalies for emergency response or further investigation. Predictive models developed in this study were generally able to predict background with medians of ± 1.0 µR/h compared to measured data, and were also able to highlight anomalous areas even where radiation exposure rates were within the range of natural background.


Assuntos
Exposição à Radiação/estatística & dados numéricos , Monitoramento de Radiação , Tecnologia de Sensoriamento Remoto , Radiação de Fundo , Raios gama
14.
Int J Radiat Biol ; 95(12): 1613-1626, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31498026

RESUMO

Purpose: The aim of this paper was to investigate the sequence preference of ionizing radiation (IR)-induced DNA damage as assessed by a linear amplification/polymerase stop (LA/PS) assay. The LA/PS assay is able to detect a wide range of IR-induced DNA lesions and this technique was utilized to quantitatively determine the preferential sites of gamma irradiation-induced DNA lesions in three different DNA sequences.Materials and methods: This analysis was performed on an automated DNA sequencer with capillary electrophoresis and laser-induced fluorescence detection.Results: The main outcome of this study was that G nucleotides were preferentially found at IR-induced polymerase stop sites. The individual nucleotides at the IR-induced DNA damage sites were analyzed and a consensus sequence of 5'-GG* (where * indicates the damaged nucleotide) was observed. In a separate method of analysis, the dinucleotides and trinucleotides at the IR-induced DNA damage sites were examined and 5'-GG* and 5'-G*G dinucleotides and 5'-GG*G trinucleotides were found to be the most prevalent. The use of the LA/PS assay permits a large number of IR-induced DNA lesions to be detected in the one procedure including: double- and single-strand breaks, apurinic/apyrimidinic sites and base damage.Conclusions: It was concluded that 2,6-diamino-4-hydroxy-5-formamidopyrimidine (Fapy-G) and the degradation products of 8-oxoG were possibly the main lesions detected. To our knowledge, this is the first occasion that the DNA sequence preference of IR-induced DNA damage as detected by a LA/PS assay has been reported.


Assuntos
Dano ao DNA , DNA Polimerase Dirigida por DNA/metabolismo , Raios gama/efeitos adversos , Sequência de Bases , Oligonucleotídeos/genética , Plasmídeos/genética
15.
Int J Radiat Biol ; 95(12): 1728-1743, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31502912

RESUMO

Purpose: This in-vitro study aimed to assess in 120 [40 community-acquired (CA-MRSA) & 80 hospital-acquired (HA-MRSA)] isolates from cancer patients whether the transmissible staphylococcal cassette chromosome mec (SCCmec) typing, and the Panton-Valentine leukocidin (PVL) virulence genes detection could be employed as tools for molecular diagnostic purposes to distinguish both methicillin-resistant Staphylococcus aureus (MRSA) categories in radiotherapy treated cancer patients.Materials and methods: SCCmec typing was determined by the combination of the type of the cassette chromosome recombinase genes (ccr) gene complex and the class of the methicillin resistance (mec) gene complex. Besides, a rapid slide latex agglutination test (LAT) and antibiotic resistance spectrum determination before and after irradiation were performed.Results: In the strict sense, with the effect of irradiation; the presence of SCCmec subtypes IVa (22.5% vs. 10.0%), b (47.5% vs. 25.0%), & d (7.5 vs. 2.5%) or type V (15.0% vs. 7.5%) genetic elements and PVL genes (p < .001) were not proved as a signature for CA-MRSA. While, the larger SCCmec types II, and III elements were not detected in 14, and 19 from the 38, and 36 typed HA-MRSA isolates (p < .001), respectively. Remarkable effects on class A & class B mec gene complex and type2, type 3 & type 5 ccr gene complex and an increase in agglutination reaction strength in response to gamma irradiation external stimulus were observed.Conclusions: Different heterogeneous genetic composition with upregulation mecA gene expression was detected after irradiation in the HA- MRSA studied population. CA-MRSA showed remarkable ability to acquire multi-antibiotic resistance after irradiation and propose a novel paradigm for future chemotherapy against the multi-resistant pathogens whose proliferation especially among immunocompromised cancer patients is on the increase.


Assuntos
Raios gama , Resistência a Meticilina/efeitos da radiação , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/efeitos da radiação , Técnicas de Diagnóstico Molecular , Neoplasias/complicações , Infecções Estafilocócicas/diagnóstico , Adolescente , Adulto , Idoso , Biomarcadores/metabolismo , Criança , Pré-Escolar , Infecção Hospitalar/complicações , Infecção Hospitalar/diagnóstico , Egito , Feminino , Humanos , Lactente , Masculino , Resistência a Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/fisiologia , Pessoa de Meia-Idade , Neoplasias/microbiologia , Infecções Estafilocócicas/complicações , Adulto Jovem
16.
Int J Mol Sci ; 20(18)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31491955

RESUMO

Japonica and indica are two important subspecies in cultivated Asian rice. Irradiation is a classical approach to induce mutations and create novel germplasm. However, little is known about the differential response between japonica and indica rice after γ radiation. Here, we utilized the RNA sequencing and Weighted Gene Co-expression Network Analysis (WGCNA) to compare the transcriptome differences between japonica Nipponbare (NPB) and indica Yangdao6 (YD6) in response to irradiation. Japonica subspecies are more sensitive to irradiation than the indica subspecies. Indica showed a higher seedling survival rate than japonica. Irradiation caused more extensive DNA damage in shoots than in roots, and the severity was higher in NPB than in YD6. GO and KEGG pathway analyses indicate that the core genes related to DNA repair and replication and cell proliferation are similarly regulated between the varieties, however the universal stress responsive genes show contrasting differential response patterns in japonica and indica. WGCNA identifies 37 co-expressing gene modules and ten candidate hub genes for each module. This provides novel evidence indicating that certain peripheral pathways may dominate the molecular networks in irradiation survival and suggests more potential target genes in breeding for universal stress tolerance in rice.


Assuntos
Raios gama , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Redes Reguladoras de Genes , Oryza/genética , Oryza/efeitos da radiação , Transcriptoma , Biologia Computacional/métodos , Dano ao DNA/genética , Perfilação da Expressão Gênica , Ontologia Genética , Tolerância a Radiação/genética , Plântula/genética , Plântula/efeitos da radiação
17.
Food Chem Toxicol ; 133: 110807, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31494133

RESUMO

Ionizing radiation (IR) resistance and toxicity to normal cells are the main problems in radiotherapy for cancer. In this study, we demonstrated that epigallocatechin gallate (EGCG) could inhibit effectively IR-induced damage to mouse normal hepatic cells AML-12, and improve dramatically the radiosensitivity of mouse hepatoma cells H22 to 60Coγ. In addition, the different effects of EGCG and underlying molecular mechanisms based on microRNA-34a (miR-34a) and apoptosis-related proteins were investigated by cells viability analysis, quantitative realtime PCR (qRT-PCR), Western blot and cells transfection. The results indicated EGCG played the key role of radiosensitization on H22 cells by activating the miR-34a/Sirt1/p53 signaling pathway. Besides, EGCG could down-regulate the expression of anti-apoptotic protein Bcl-2, and up-regulate the expression of pro-apoptotic proteins Bax and Caspase-3 in H22 cells. Interestingly, EGCG showed contrary results on AML-12 cells. Therefore, radiation protection and radiosensitization of EGCG were associated with apoptosis regulated by miR-34a/Sirt1/p53 signaling pathway.


Assuntos
Catequina/análogos & derivados , Protetores contra Radiação/farmacologia , Radiossensibilizantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Catequina/farmacologia , Linhagem Celular Tumoral , Radioisótopos de Cobalto , Regulação para Baixo/efeitos dos fármacos , Raios gama , Camundongos , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacos , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
18.
Radiat Res ; 192(4): 440-450, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31393823

RESUMO

Radiotherapy to treat brain tumors can potentially harm the central nervous system (CNS). The radiation stimulates a series of immune responses in both the CNS as well as peripheral immune system. To date, studies have mostly focused on the changes occurring in the immune response within the CNS. In this study, we investigated the effect of γ-ray-induced CNS injury on the peripheral immune response using a cell co-culture model and a whole-brain irradiation (WBI) rat model. Nerve cells (SH-SY5Y and U87 MG cells) were γ-ray irradiated, then culture media of the irradiated cells (conditioned media) was used to culture immune cells (THP-1 cells or Jurkat cells). Analyses were performed based on the response of immune cells in conditioned media. Sprague-Dawley rats received WBI at different doses, and were fed for one week to one month postirradiation. Spleen and peripheral blood were then isolated and analyzed. We observed that the number of monocytes in peripheral blood, and the level of NK cells and NKT cells in spleen increased after CNS injury. However, the level of T cells in spleen did not change and the level of B cells in the spleen decreased after γ-ray-induced CNS injury. These findings indicate that CNS injury caused by ionizing radiation induces a series of changes in the peripheral immune system.


Assuntos
Sistema Nervoso Central/lesões , Sistema Nervoso Central/efeitos da radiação , Raios gama/efeitos adversos , Lesões Experimentais por Radiação/imunologia , Animais , Diferenciação Celular/efeitos da radiação , Linhagem Celular Tumoral , Sistema Nervoso Central/patologia , Quimiocinas/sangue , Quimiotaxia/efeitos da radiação , Humanos , Imunidade Inata/efeitos da radiação , Masculino , Lesões Experimentais por Radiação/sangue , Lesões Experimentais por Radiação/patologia , Ratos , Ratos Sprague-Dawley , Irradiação Corporal Total/efeitos adversos
19.
Int J Radiat Oncol Biol Phys ; 105(4): 852-860, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31394167

RESUMO

PURPOSE: Postoperative radiation therapy (RT) delivered to lymphatics is associated with an increased risk of developing lymphedema. Reported effects of RT on lymphatic vessels have varied, however, possibly because of the use of different animal models with varying surgery and radiation schedules and the inability to directly and longitudinally image lymphatics in vivo. Here we report, using noninvasive imaging, changes in lymphatic remodeling and function in response to surgery and RT in a mouse model. METHODS AND MATERIALS: Popliteal lymphadenectomy in mice preceded single-dose gamma irradiation of the lower extremity at a single dose of 0, 20, or 40 Gy. The right hind limb of intact mice was also radiated with 4 fractions (4 × 5 Gy). Near-infrared fluorescence lymphatic imaging with indocyanine green was performed over 6 months to monitor lymphatic vessel remodeling. RESULTS: Postoperative mice treated with 20 Gy showed transient changes in lymphatic drainage, exacerbated vessel remodeling including qualitative vessel dilation and abnormal indocyanine green pooling from week 1 to 2, and initiation of restoration of lymphatic vessels, although dermal backflow was occasionally observed. Mice treated with 40 Gy showed steadily increasing lymphatic impairment until week 3 and extravasation of dye and dermal backflow in weeks 4 to 25. The ankles of mice treated with 40 Gy were significantly swollen from weeks 2 to 4 as compared with mice treated with 0 Gy or 20 Gy. Mice that received fractionated RT exhibited lymphatic vessel remodeling similar to remodeling that occurred when a single 20 Gy dose was given; however, dermal backflow did not resolve as it did in the case of a single 20 Gy dose. CONCLUSIONS: The degree of nonreversing lymphatic damage seen in our mouse model was dependent on RT dose. Our results suggest that near-infrared fluorescence lymphatic imaging detection of early lymphatic changes can be used to predict development of lymphedema in patients with cancer.


Assuntos
Excisão de Linfonodo/efeitos adversos , Irradiação Linfática/efeitos adversos , Vasos Linfáticos/efeitos da radiação , Linfedema/etiologia , Animais , Tornozelo/diagnóstico por imagem , Corantes/administração & dosagem , Relação Dose-Resposta à Radiação , Feminino , Raios gama , Verde de Indocianina/administração & dosagem , Extremidade Inferior/diagnóstico por imagem , Extremidade Inferior/efeitos da radiação , Extremidade Inferior/cirurgia , Linfa/fisiologia , Excisão de Linfonodo/métodos , Vasos Linfáticos/diagnóstico por imagem , Vasos Linfáticos/patologia , Vasos Linfáticos/fisiopatologia , Linfografia/métodos , Masculino , Camundongos , Modelos Animais , Imagem Óptica/métodos , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Doses de Radiação , Fatores de Tempo
20.
Planta ; 250(5): 1567-1590, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31372744

RESUMO

MAIN CONCLUSION: Persistent DNA damage in gamma-exposed Norway spruce, Scots pine and Arabidopsis thaliana, but persistent adverse effects at the organismal and cellular level in the conifers only. Gamma radiation emitted from natural and anthropogenic sources may have strong negative impact on plants, especially at high dose rates. Although previous studies implied different sensitivity among species, information from comparative studies under standardized conditions is scarce. In this study, sensitivity to gamma radiation was compared in young seedlings of the conifers Scots pine and Norway spruce and the herbaceous Arabidopsis thaliana by exposure to 60Co gamma dose rates of 1-540 mGy h-1 for 144 h, as well as 360 h for A. thaliana. Consistent with slightly less prominent shoot apical meristem, in the conifers growth was significantly inhibited with increasing dose rate ≥ 40 mGy h-1. Post-irradiation, the conifers showed dose-rate-dependent inhibition of needle and root development consistent with increasingly disorganized apical meristems with increasing dose rate, visible damage and mortality after exposure to ≥ 40 mGy h-1. Regardless of gamma duration, A. thaliana showed no visible or histological damage or mortality, only delayed lateral root development after ≥ 100 mGy h-1 and slightly, but transiently delayed post-irradiation reproductive development after ≥ 400 mGy h-1. In all species dose-rate-dependent DNA damage occurred following ≥ 1-10 mGy h-1 and was still at a similar level at day 44 post-irradiation. In conclusion, the persistent DNA damage (possible genomic instability) following gamma exposure in all species may suggest that DNA repair is not necessarily mobilized more extensively in A. thaliana than in Norway spruce and Scots pine, and the far higher sensitivity at the organismal and cellular level in the conifers indicates lower tolerance to DNA damage than in A. thaliana.


Assuntos
Arabidopsis/efeitos da radiação , Raios gama/efeitos adversos , Picea/efeitos da radiação , Pinus sylvestris/efeitos da radiação , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Noruega , Picea/genética , Picea/crescimento & desenvolvimento , Pinus sylvestris/genética , Pinus sylvestris/crescimento & desenvolvimento , Plântula/genética , Plântula/efeitos da radiação
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