Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.078
Filtrar
1.
Mutat Res ; 856-857: 503220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32928367

RESUMO

We assessed the radioprotective and mitigative actions of sodium diclofenac, a non-steroidal anti-inflammatory drug using cultured human peripheral blood as a model. Both pre- and post-irradiation treatments with the drug reduced gamma radiation-induced formation of dicentric chromosome, cytochalasin-blocked micronuclei and γ-H2AX foci in human peripheral blood lymphocytes. This work supports the concept that sodium diclofenac may be a useful radiation countermeasure agent.


Assuntos
Diclofenaco/farmacologia , Relação Dose-Resposta à Radiação , Histonas/genética , Protetores contra Radiação/farmacologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Aberrações Cromossômicas/efeitos dos fármacos , Aberrações Cromossômicas/efeitos da radiação , Análise Citogenética/métodos , Reposicionamento de Medicamentos , Raios gama/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Linfócitos/efeitos dos fármacos , Linfócitos/efeitos da radiação
2.
Life Sci ; 260: 118410, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32926927

RESUMO

AIMS: Methylsulfonylmethane (MSM), is an organosulfur compound, has many health benefits. Bisphenol-A (BPA) and γ-radiation (R) are two risky environmental contaminants that human beings are exposed to in everyday life. This work aims at unveiling the modulatory role of MSM in combating BPA and R co-exposure induced neurodegenerative disorder (Alzheimer's (AD)-mimic neurotoxicity). MAIN METHODS: Female rats were randomly divided into five groups. One group was normal control and the other four groups were subjected to subacute BPA intoxication and/or exposed to fractionated weekly doses of R for 4 weeks and either untreated or treated with MSM concomitantly. KEY FINDINGS: BPA and R co-exposure induced typical hallmarks of neurodegenerative disorders as revealed by tremendously elevated oxidative stress, extensive neuroinflammation (tumor necrosis factor -α and interleukin-1ß), elevated AD markers (amyloid-beta (Aß42), acetylcholinesterase (AchE) activity and tau-phosphorylation) in cortex and hippocampus as well as up-regulation of microglial pro-inflammatory triggering receptor expressed on myeloid cell-2(TREM-2)/DNAX-activating protein of 12 kDa (DAP-12)/spleen-tyrosine kinase (Syk) pathway and its downstream targets (PLC-γ/DAG/p38-MAPK) in hippocampus. Also, neurodegenerative lesions were revealed in histopathological examination of cortex and hippocampus coupled with marked Aß deposition in hippocampus. Whereas, MSM treatment improved histopathological insults and ameliorated level of oxidative stress, neuroinflammation and AD markers as well as modulated TREM-2/DAP-12/Syk pathway. SIGNIFICANCE: Our data suggest that MSM afforded neuroprotection against BPA and R; supporting its potential application in the associated neurodegenerative disorders.


Assuntos
Compostos Benzidrílicos/toxicidade , Dimetil Sulfóxido/farmacologia , Raios gama/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Glicoproteínas de Membrana/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Fenóis/toxicidade , Receptores Imunológicos/metabolismo , Sulfonas/farmacologia , Quinase Syk/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Estrogênios não Esteroides/toxicidade , Feminino , Glicoproteínas de Membrana/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/patologia , Ratos , Ratos Wistar , Receptores Imunológicos/genética , Quinase Syk/genética
3.
PLoS One ; 15(6): e0233967, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497067

RESUMO

Radiation-induced heart disease presents a significant challenge in the event of an accidental radiation exposure as well as to cancer patients who receive acute doses of irradiation as part of radiation therapy. We utilized the spontaneously hypertensive Wistar-Kyoto rat model, previously shown to demonstrate drug-induced cardiomyopathy, to evaluate the acute and long-term effects of sub-lethal total body gamma irradiation at two, four, and fifty-two weeks. We further examined irreversible oxidative protein carbonylation in the heart immediately following irradiation in the normotensive Wistar-Kyoto rat. Both males and females sustained weight loss and anemic conditions compared to untreated controls over a one-year period as reflected by reduced body weight and low red blood cell count. Increased inflammation was detected by elevated IL-6 serum levels selectively in males at four weeks. Serum cardiac troponin T and I analyses revealed signs of cardiomyopathy at earlier timepoints, but high variability was observed, especially at one year. Echocardiography at two weeks following 5.0Gy treatment revealed a significant decrease in cardiac output in females and a significant decrease in both diastolic and systolic volumes in males. Following 10.0Gy irradiation in the normotensive Wistar-Kyoto rat, the heart tissue showed an increase in total protein oxidative carbonylation accompanied by DNA damage indicated by an increase in γ-H2AX. Using proteomic analyses, we identified several novel proteins which showed a marked difference in carbonylation including those of mitochondrial origin and most notably, cardiac troponin T, one of the key proteins involved in cardiomyocyte contractility. Overall, we present findings of acute oxidative protein damage, DNA damage, cardiac troponin T carbonylation, and long-term cardiomyopathy in the irradiated animals.


Assuntos
Raios gama/efeitos adversos , Coração/efeitos da radiação , Oxirredução/efeitos da radiação , Carbonilação Proteica/efeitos da radiação , Proteínas/química , Animais , Feminino , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Irradiação Corporal Total/efeitos adversos
4.
Life Sci ; 253: 117749, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32380079

RESUMO

AIM: This work aims to explore the role of diminazene aceturate (DIZE) in the enhancement of angiotensin-converting enzyme-2 (ACE2) to prevent the inflammatory and fibrotic response induced by γ-irradiation through activating the protective axis ACE2/angiotensin (1-7)/Mas receptor (ACE2/Ang(1-7)/Mas). METHODS: Male rats were injected i.p. with 15 mg/kg DIZE daily for 7 days pre and post-irradiation, where 7.5 Gy of γ-radiation as a single dose was used. KEY FINDINGS: Gamma radiation induced a significant elevation of renal biochemical parameters: urea, creatinine and blood urea nitrogen (BUN) in serum with a significant disturbance in oxidative stress markers: elevation in malondialdehyde (MDA) associated with a depletion of reduced glutathione (GSH) and superoxide dismutase (SOD). Beside elevation in the level of angiotensin II (AngII) that lead to remarkably increases in the levels of the renal inflammatory mediators: tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB) and interleukin-1ß (IL-1ß) as well as renal fibrogenic markers: transforming growth factor-ß1 (TGF-ß1), connective tissue growth factor (CTGF), and hydroxyproline content in the renal tissues. DIZE caused marked expansion in the expression of ACE2 consequently decreased the expression of AngII and increased the expression of Ang(1-7) which through its Mas receptor ameliorates the biochemical and histopathological damage induced by radiation. SIGNIFICANCE: DIZE-induced stimulation of ACE2 subdues the renal deleterious consequences induced by γ-radiation via activation of ACE2/Ang(1-7)/Mas axis in rats.


Assuntos
Angiotensina II/metabolismo , Diminazena/análogos & derivados , Raios gama/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Peptidil Dipeptidase A/metabolismo , Angiotensina I/metabolismo , Angiotensina II/administração & dosagem , Animais , Diminazena/farmacologia , Glutationa/metabolismo , Masculino , Fragmentos de Peptídeos/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas-G/metabolismo , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo
5.
Exp Hematol ; 84: 54-66, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32240658

RESUMO

Exposure to high-dose total body irradiation (TBI) can result in hematopoietic acute radiation syndrome (H-ARS), characterized by leukopenia, anemia, and coagulopathy. Death from H-ARS occurs from hematopoietic insufficiency and opportunistic infections. Following radiation exposure, red blood cells (RBCs) undergo hemolysis from radiation-induced hemoglobin denaturation, causing the release of iron. Free iron can have multiple detrimental biological effects, including suppression of hematopoiesis. We investigated the impact of radiation-induced iron release on the bone marrow following TBI and the potential impact of the ACE inhibitor captopril, which improves survival from H-ARS. C57BL/6J mice were exposed to 7.9 Gy, 60Co irradiation, 0.6 Gy/min (LD70-90/30). RBCs and reticulocytes were significantly reduced within 7 days of TBI, with the RBC nadir at 14-21 days. Iron accumulation in the bone marrow correlated with the time course of RBC hemolysis, with an ∼10-fold increase in bone marrow iron at 14-21 days post-irradiation, primarily within the cytoplasm of macrophages. Iron accumulation in the bone marrow was associated with increased expression of genes for iron binding and transport proteins, including transferrin, transferrin receptor 1, ferroportin, and integrin αMß2. Expression of the gene encoding Nrf2, a transcription factor activated by oxidative stress, also increased at 21 days post-irradiation. Captopril did not alter iron accumulation in the bone marrow or expression of iron storage genes, but did suppress Nrf2 expression. Our study suggests that following TBI, iron is deposited in tissues not normally associated with iron storage, which may be a secondary mechanism of radiation-induced tissue injury.


Assuntos
Síndrome Aguda da Radiação/metabolismo , Medula Óssea/metabolismo , Raios gama/efeitos adversos , Hematopoese/efeitos da radiação , Ferro/metabolismo , Lesões Experimentais por Radiação/metabolismo , Síndrome Aguda da Radiação/genética , Síndrome Aguda da Radiação/patologia , Animais , Medula Óssea/patologia , Captopril/farmacologia , Eritrócitos/metabolismo , Eritrócitos/patologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Hematopoese/efeitos dos fármacos , Hematopoese/genética , Camundongos , Camundongos Transgênicos , Fator 2 Relacionado a NF-E2/biossíntese , Fator 2 Relacionado a NF-E2/genética , Lesões Experimentais por Radiação/genética , Lesões Experimentais por Radiação/patologia
6.
Radiat Res ; 193(5): 451-459, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32150497

RESUMO

Findings from previous studies have suggested that the telomerase system is involved in radiation-induced genomic instability. In this study, we investigated the involvement of telomerase in the development and processing of chromosomal damage at different cell cycle stages after irradiation of human fibroblasts. Several response criteria were investigated, including cell survival, chromosomal damage (using the micronucleus assay), G2-induced chromatid aberrations (using the conventional G2 assay as well as a chemically-induced premature chromosome condensation assay) and DNA double-strand breaks (DSBs; using γ-H2AX, 53BP1 and Rad51) in an isogenic pair of cell lines: BJ human foreskin fibroblasts and BJ1-hTERT, a telomerase-immortalized BJ cell line. To distinguish among G1, S and G2 phase, cells were co-immunostained for CENP-F and cyclin A, which are tightly regulated proteins in the cell cycle. After X-ray irradiation at doses in the range of 0.1-6 Gy, the results showed that for cell survival and micronuclei induction, where the overall effect is dominated by the cells in G1 and S phase, no difference was observed between the two cell types; in contrast, when radiation sensitivity at the G2 stage of the cell cycle was analyzed, a significantly higher number of chromatid-type aberrations (breaks and exchanges), and higher levels of γ-H2AX and of Rad51 foci were observed for the BJ cells compared to the BJ1-hTERT cells. Therefore, it can be concluded that telomerase appears to be involved in DNA DSB repair processes, mainly in the G2 phase. These data, taken overall, reinforce the notion that hTERT or other elements of the telomere/telomerase system may defend chromosome integrity in human fibroblasts by promoting repair in G2 phase of the cell cycle.


Assuntos
Instabilidade Genômica/efeitos da radiação , Telomerase/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos da radiação , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Fase G2/efeitos da radiação , Raios gama/efeitos adversos , Humanos , Testes para Micronúcleos , Rad51 Recombinase/metabolismo , Fase S/efeitos da radiação
7.
Cytogenet Genome Res ; 160(2): 100-109, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32146470

RESUMO

Chloroplasts and mitochondria are semi-autonomous organelles and have their own genomes (cytoplasmic genomes). Physical radiations (e.g., γ-rays) have been widely used in artificial mutation induction for plant germplasm enhancement and for breeding new cultivars. However, little is known at the genomic level about which kind of cytoplasmic mutations and/or characteristics could be induced in plants. The present study aimed to investigate the type, number, and distribution of inheritable cytoplasmic mutations induced by γ-rays in rice (Oryza sativa L.). Six plants were selected from the 2nd generation (M2) populations after γ-ray (137Cs) irradiation of the rice cultivar Nipponbare, 2 each for the 3 irradiation doses (150, 250, and 350 Gy), and their genomes were sequenced on an Illumina platform. Together with the whole-genome sequencing data of 3 external Nipponbare control plants, single-base substitutions (SBSs) and insertions/deletions (InDels) in chloroplast (cp) and mitochondrial (mt) genomes were identified and analyzed in-depth using bioinformatic tools. The majority of SBSs and InDels identified were background mutations in the 6 M2 plants, and the number of induced mutations varied greatly among the plants. Most induced mutations were present in a heterogeneous state, reflecting the fact that multiple cp and mt copies existed in the progenitor cells. The induced mutations were distributed in different genomic regions in the 6 M2 plants, including exonic regions, but none of them was predicted to cause nonsynonymous mutations or frameshifts. Our study thus revealed, at the genomic level, characteristics of cytoplasmic mutations induced by γ-rays in rice.


Assuntos
Raios gama/efeitos adversos , Mutação , Oryza/efeitos da radiação , Sequenciamento Completo do Genoma/métodos , Cloroplastos/genética , Cloroplastos/efeitos da radiação , Genoma de Planta/efeitos da radiação , Sequenciamento de Nucleotídeos em Larga Escala , Mitocôndrias/genética , Mitocôndrias/efeitos da radiação , Oryza/genética , Proteínas de Plantas/genética , Proteínas de Plantas/efeitos da radiação , Sementes/genética , Sementes/efeitos da radiação
8.
Radiat Res ; 193(6): 560-568, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32216709

RESUMO

Chemical-induced premature chromosome condensation (PCC) is an alternative biodosimetry method to the gold-standard dicentric analysis for ionizing radiation. However, existing literature shows great variations in the experimental protocols which, together with the different scoring criteria applied in individual studies, result in large discrepancies in the coefficients of the calibration curves. The current study is based on an extensive review of the peer-reviewed literature on the chemical-induced ring PCC (rPCC) assay for high-dose exposure. For the first time, a simplified yet effective protocol was developed and tested in an attempt to reduce the scoring time and to increase the accuracy of dose estimation. Briefly, the protein phosphatase inhibitor, calyculin A, was selected over okadaic acid for higher efficiency. Colcemid block was omitted and only G2-PCC cells were scored. Strict scoring criteria for total rings and hollow rings only were described to minimize the uncertainty resulting from scoring ring-like artefacts. It was found that ring aberrations followed a Poisson distribution and the dose-effect relationship favored a linear fit with an α value of 0.0499 ± 0.0028 Gy-1 for total rings and 0.0361 ± 0.0031 Gy-1 for hollow rings only. The calibration curves constructed by scoring ring aberrations were directly compared between the simplified calyculin A-induced PCC protocol and that of the cell fusion-induced PCC for high-dose exposure to gamma rays. The technical practicalities of these two methods were also compared; and our blind validation tests showed that both assays were feasible for high-dose γ-ray exposure assessment even when only hollow rings in 100 PCC spreads were scored.


Assuntos
Aberrações Cromossômicas/induzido quimicamente , Aberrações Cromossômicas/efeitos da radiação , Raios gama/efeitos adversos , Oxazóis/efeitos adversos , Adulto , Relação Dose-Resposta à Radiação , Humanos , Masculino , Pessoa de Meia-Idade , Radiometria
9.
Ecotoxicol Environ Saf ; 192: 110261, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32018153

RESUMO

The Chlorella vulgaris has been generally recognized as a promising microalgal model to study stress-related responses due to its ability to withstand against ionizing and non-ionizing radiation. The objective of the present study was to investigate the effect of CaCl2 pre-treatment at different concentrations on the responses of microalga C. vulgaris under gamma radiation toxicity. Changes in growth, physiological parameters and biochemical compositions of the algae pretreated with 0.17 (normal), 5, and 10 mM CaCl2 were analyzed under 300 Gy gamma irradiation and compared to those of gamma-free control. The results showed that parameters including specific growth rate, cell size, chlorophyll and protein contents, ascorbate peroxidase (APX), and superoxide dismutase (SOD) activity, Ferric Reducing Antioxidant Power (FRAP), and the ratios of nucleic acid to protein negatively affected by gamma irradiation. All these parameters, except for the ratios of nucleic acid to protein significantly increased in the algae when pretreated with a CaCl2 content higher than normal concentration. The analysis also showed that parameters including catalase activity, proline, and carotenoid content, the level of lipid peroxidation, and electrolyte leakage (EL) significantly increased under gamma irradiation but not affected significantly under different CaCl2 pre-treatments. Additionally, specific growth rate, chlorophyll a and protein content, APX and SOD activity, FRAP, lipid peroxidation, electrolyte leakage, and the ratios of nucleic acid to protein were the only parameters that significantly affected by the interaction of gamma toxicity and CaCl2 pretreatment. Overall, the results suggested that regardless of the CaCl2 effect, the algal cells responded to gamma radiation more efficiently by increasing proline, carotenoids content, and CAT activity. More important, it was concluded that calcium had an essential role in modifying the detrimental effect of gamma toxicity on the algae mainly by increasing the activity of ascorbate peroxidase and superoxide dismutase and maintaining the reducing antioxidant power (FRAP) of the cells at a high level.


Assuntos
Cloreto de Cálcio/farmacologia , Chlorella vulgaris/efeitos da radiação , Raios gama/efeitos adversos , Tolerância a Radiação/efeitos dos fármacos , Antioxidantes/metabolismo , Ascorbato Peroxidases/metabolismo , Carotenoides/metabolismo , Catalase/metabolismo , Chlorella vulgaris/efeitos dos fármacos , Chlorella vulgaris/crescimento & desenvolvimento , Chlorella vulgaris/metabolismo , Clorofila/metabolismo , Clorofila A/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Microalgas/efeitos dos fármacos , Microalgas/crescimento & desenvolvimento , Microalgas/metabolismo , Microalgas/efeitos da radiação , Prolina/metabolismo , Superóxido Dismutase/metabolismo
10.
Mutat Res ; 849: 503141, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32087855

RESUMO

The inherent capacity of individuals to efficiently repair ionizing radiation induced DNA double strand breaks (DSBs) may be inherited, however, it is influenced by several epigenetic and environmental factors. A pilot study tested whether chronic low dose natural radiation exposure influences the rejoining of initial DNA DSBs induced by a 2 Gy γ-irradiation in 22 individuals from high (>1.5 mGy/year) and normal (≤1.5 mGy/year) level natural radiation areas (H&NLNRA) of Kerala. Rejoining of DSBs (during 1 h at 37 °C, immediately after irradiation) was evaluated at the chromosome level in the presence and absence of wortmannin (a potent inhibitor of DSB repair in normal human cells) using a cell fusion-induced premature chromosome condensation (PCC) assay. The PCC assay quantitates DSBs in the form of excess chromosome fragments in human G0 lymphocytes without the requirement for cell division. A quantitative difference was observed in the early rejoining of DNA DSBs between individuals from HLNRA and NLNRA, with HLNRA individuals showing a higher (P = 0.05) mean initial repair ratio. The results indicate an influence of chronic low dose natural radiation on initial DNA DSB repair in inhabitants of HLNRA of the Kerala coast.


Assuntos
Radiação de Fundo/efeitos adversos , Bioensaio , Reparo do DNA/efeitos dos fármacos , Raios gama/efeitos adversos , Linfócitos/efeitos da radiação , Adulto , Animais , Células CHO , Fusão Celular , Cromossomos Humanos/efeitos dos fármacos , Cromossomos Humanos/efeitos da radiação , Cricetulus , DNA/genética , DNA/metabolismo , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Humanos , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Masculino , Projetos Piloto , Cultura Primária de Células , Doses de Radiação , Wortmanina/farmacologia
11.
Radiat Res ; 193(4): 372-382, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32097100

RESUMO

A standard Fricke dosimeter was used to measure the absorbed dose via the oxidation yields of Fe3+ ions in an aqueous environment induced by soft X rays within the "water window" spectral range. We also exploited the property of a neutral solution containing terephthalic acid as a tool for selective detection of OH radicals. Both dosimetric systems were irradiated using the experimental pulsed laser-plasma soft X-ray source as well as conventional 1.25-MeV gamma rays. Radiation chemical yields of Fe3+ ions and OH radicals were determined to be (5.13 ± 0.94) × 10-1 µmol·J-1 (4.95 ± 0.91 100eV-1) and (2.33 ± 0.35) × 10-2 µmol·J-1 (0.23 ± 0.03 100eV-1), respectively. Measurements were supported by Monte Carlo simulations to estimate the linear energy transfer of the water window radiation. The simulation results are in good agreement with expected linear energy transfer of ions inducing the same Fe3+ ion and OH radical radiation chemical yield.


Assuntos
Radical Hidroxila/química , Ferro/química , Radiometria , Raios X/efeitos adversos , Raios gama/efeitos adversos , Humanos , Radical Hidroxila/efeitos da radiação , Íons/química , Transferência Linear de Energia , Método de Monte Carlo , Oxirredução , Água/química
12.
Bull Entomol Res ; 110(4): 497-505, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32000866

RESUMO

Irradiation is a physical, environmentally friendly treatment which does not leave any residues in the product. It is increasingly used as an alternative to methyl bromide and other chemical fumigants for disinfestation of insect pest in stored grains. In this research, we try to evaluate the effect of low gamma irradiation doses in the range of 50-1200 Gy on the different stages of Callosobruchus maculatus. It was found that no adults emerged after irradiation of eggs at 450 Gy. No emerging adults (F1 generation) have been shown when larvae or pupae were exposed to 650 Gy. Also, no emerging adult has been shown from the parental C. maculatus adults irradiated with 650 Gy. When suppression of F1 generation was used for the measuring effective irradiation dose and phytosanitary efficacy, 650 Gy was required for disinfestation of cowpea seed weevils. The irradiation dose level of 650 Gy was used for the large-scale confirmatory tests applied to 27,754 adults of C. maculatus in cowpea seeds resulting in non F1 adults' production with a confidence level of 93.77%. All the physical and chemical characteristics of cowpea seeds were non-significantly (P ≤ 0.05) affected by the irradiation dose of 650 Gy. Meanwhile, this irradiation dose very slightly reduced the microbial load of cowpea seeds. We recommend the generic dose 650 Gy as the phytosanitary irradiation dose for the cowpea seed weevil.


Assuntos
Besouros/efeitos da radiação , Vigna/efeitos da radiação , Animais , Besouros/crescimento & desenvolvimento , Feminino , Raios gama/efeitos adversos , Controle de Insetos , Larva/efeitos da radiação , Masculino , Óvulo/efeitos da radiação , Pupa/efeitos da radiação , Sementes/efeitos da radiação
13.
Int J Radiat Oncol Biol Phys ; 107(1): 202-211, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32036005

RESUMO

PURPOSE: Exposure to ionizing radiation increases risk of breast cancer. Although proton radiation is encountered in outer space and in medicine, we do not fully understand breast cancer risks from protons owing to limited in vivo data. The purpose of this study was to comparatively assess the effects of γ-rays and protons on mammary tumorigenesis in APCMin/+ mice. METHODS AND MATERIALS: Female APCMin/+ mice were exposed to 1 GeV protons (1.88 or 4.71 Gy) and 137Cs γ-rays (2 or 5 Gy). Mice were euthanized 100 to 110 days after irradiation, at which point mammary tumors were scored, tumor grades were assessed, and relative biological effectiveness was calculated. Molecular phenotypes were determined by assessing estrogen receptor α (ERα) and human epidermal growth factor receptor 2 (HER2) status. ERα downstream signaling was assessed by immunohistochemistry. RESULTS: Exposure to proton radiation led to increased mammary tumor frequency at both proton radiation doses compared with γ-rays. The calculated relative biological effectiveness for proton radiation-induced mammary tumorigenesis was 3.11 for all tumors and >5 for malignant tumors relative to γ-rays. Tumor frequency per unit of radiation was higher at the lower dose, suggesting a saturation effect at the higher dose. Protons induced more adenocarcinomas relative to γ-rays, and proton-induced tumors show greater ERα and HER2 positivity and higher activation of the ERα downstream PI3K/Akt and cyclin D1 pathways relative to γ-rays. CONCLUSIONS: Our data demonstrate that protons pose a higher risk of mammary tumorigenesis relative to γ-rays. We also show that proton radiation-induced tumors in APCMin/+ mice are ERα- and HER2-positive, which is consistent with our previous data on radiation-induced estrogenic response in wild-type mice. Although this study establishes APCMin/+ as a model with adequate signal-to-noise ratio for space radiation-induced mammary tumorigenesis, further studies will be required to address the uncertainties in space radiation-induced breast cancer risk estimation.


Assuntos
Carcinogênese/efeitos da radiação , Receptor alfa de Estrogênio/metabolismo , Raios gama/efeitos adversos , Neoplasias Mamárias Experimentais/patologia , Terapia com Prótons/efeitos adversos , Receptor ErbB-2/metabolismo , Eficiência Biológica Relativa , Animais , Feminino , Neoplasias Mamárias Experimentais/etiologia , Neoplasias Mamárias Experimentais/metabolismo , Camundongos
14.
Int J Mol Sci ; 21(3)2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32041250

RESUMO

The present study aimed to explore the possible radioprotective effects of celastrol and relevant molecular mechanisms in an in vitro cell and in vivo mouse models exposed to gamma radiation. Human keratinocytes (HaCaT) and foreskin fibroblast (BJ) cells were exposed to gamma radiation of 20Gy, followed by treatment with celastrol for 24 h. Cell viability, reactive oxygen species (ROS), nitric oxide (NO) and glutathione (GSH) production, lipid peroxidation, DNA damage, inflammatory cytokine levels, and NF-κB pathway activation were examined. The survival rate, levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in blood, and p65 and phospho-p65 expression were also evaluated in mice after exposure to gamma radiation and celastrol treatment. The gamma irradiation of HaCaT cells induced decreased cell viability, but treatment with celastrol significantly blocked this cytotoxicity. Gamma irradiation also increased free radical production (e.g., ROS and NO), decreased the level of GSH, and enhanced oxidative DNA damage and lipid peroxidation in cells, which were effectively reversed by celastrol treatment. Moreover, inflammatory responses induced by gamma irradiation, as demonstrated by increased levels of IL-6, TNF-α, and IL-1ß, were also blocked by celastrol. The increased activity of NF-κB DNA binding following gamma radiation was significantly attenuated after celastrol treatment. In the irradiated mice, treatment with celastrol significantly improved overall survival rate, reduced the excessive inflammatory responses, and decreased NF-κB activity. As a NF-κB pathway blocker and antioxidant, celastrol may represent a promising pharmacological agent with protective effects against gamma irradiation-induced injury.


Assuntos
Prepúcio do Pênis/citologia , Raios gama/efeitos adversos , Queratinócitos/citologia , Protetores contra Radiação/farmacologia , Triterpenos/farmacologia , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Modelos Animais de Doenças , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/imunologia , Fibroblastos/efeitos da radiação , Prepúcio do Pênis/efeitos dos fármacos , Prepúcio do Pênis/imunologia , Prepúcio do Pênis/efeitos da radiação , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Glutationa/efeitos da radiação , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Queratinócitos/efeitos da radiação , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Fator de Necrose Tumoral alfa/metabolismo
15.
Sci Rep ; 10(1): 1757, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019942

RESUMO

Bone marrow failure and hematopoietic damage is one of the major consequences of irradiation-induced lethality. There is an immediate need to develop medical countermeasures (MCMs) to combat irradiation-induced lethality. We tested the efficacy of CDX-301, developed by Celldex Therapeutics Inc., in mice exposed to Co-60 gamma total body irradiation (TBI). The drug demonstrated its efficacy both as a prophylactic countermeasure and a mitigator in CD2F1 mice exposed to TBI. A single dose of CDX-301 administered 24 h prior to 24 h post-exposure conferred significant survival. Accelerated recovery from irradiation-induced peripheral blood cytopenia, bone marrow damage as well as apoptosis in sternum was observed in mice pre-treated with CDX-301. Analysis of splenocytes revealed alterations in T cell profiles that were dependent on the time of drug administration. Prophylactic treatment of CDX-301 resulted in increased splenic CD3+ T cells, specifically CD4+T helper cells, compared to splenocytes from non-irradiated mice. These results indicate that CDX-301 is a promising radiation countermeasure and demonstrate its capability to protect cells within hematopoietic organs. These data support potential use of CDX-301, both pre- and post-radiation, against hematopoietic acute radiation syndrome with a broad window for medical management in a radiological or nuclear event.


Assuntos
Síndrome Aguda da Radiação/tratamento farmacológico , Medula Óssea/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Protetores contra Radiação/farmacologia , Animais , Raios gama/efeitos adversos , Masculino , Contramedidas Médicas , Camundongos , Irradiação Corporal Total/efeitos adversos
16.
Cancer Sci ; 111(3): 840-848, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31925975

RESUMO

Ionizing radiation can damage DNA and, therefore, is a risk factor for cancer. Eker rats, which carry a heterozygous germline mutation in the tumor-suppressor gene tuberous sclerosis complex 2 (Tsc2), are susceptible to radiation-induced renal carcinogenesis. However, the molecular mechanisms involved in Tsc2 inactivation are unclear. We subjected Fischer 344 × Eker (Long Evans Tsc2+/- ) F1 hybrid rats to gamma-irradiation (2 Gy) at gestational day 19 (GD19) or postnatal day 5 (PND5) and investigated the patterns of genomic alterations in the Tsc2 allele of renal tumors that developed at 1 year after irradiation (N = 24 tumors for GD19, N = 10 for PND5), in comparison with spontaneously developed tumors (N = 8 tumors). Gamma-irradiation significantly increased the multiplicity of renal tumors. The frequency of LOH at the chromosome 10q12 region, including the Tsc2 locus, was 38%, 29% and 60% in renal carcinomas developed from the nonirradiated, GD19 and PND5 groups, respectively. Array comparative genomic hybridization analysis revealed that the LOH patterns on chromosome 10 in renal carcinomas were classified into chromosomal missegregation, mitotic recombination and chromosomal deletion types. LOH of the interstitial chromosomal deletion type was observed only in radiation-associated carcinomas. Sequence analysis for the wild-type Tsc2 allele in the LOH-negative carcinomas identified deletions (nonirradiated: 26%; GD19: 21%) and base-substitution mutations (GD19: 4%). Reduced expression of Tsc2 was also observed in the majority of the LOH-negative carcinomas. Our results suggest that interstitial chromosomal deletion is a characteristic mutagenic event caused by ionizing radiation, and it may contribute to the assessment of radiation-induced cancer risk.


Assuntos
Neoplasias Renais/genética , Proteína 2 do Complexo Esclerose Tuberosa/genética , Esclerose Tuberosa/genética , Alelos , Animais , Deleção Cromossômica , Cromossomos Humanos Par 10/genética , Hibridização Genômica Comparativa/métodos , Raios gama/efeitos adversos , Heterozigoto , Humanos , Masculino , Mutação/genética , Ratos , Ratos Endogâmicos F344 , Ratos Long-Evans , Risco , Proteínas Supressoras de Tumor/genética
17.
J Immunol ; 204(5): 1255-1262, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31941655

RESUMO

Gut bacteria-associated sepsis is a serious concern in patients with gastrointestinal acute radiation syndrome (GIARS). In our previous studies, gut bacteria-associated sepsis caused high mortality rates in mice exposed to 6-9 Gy of γ-rays. IL-12+CD38+ iNOS+ Mϕ (M1Mϕ) located in the bacterial translocation site (mesenteric lymph nodes [MLNs]) of unirradiated mice were characterized as host defense antibacterial effector cells. However, cells isolated from the MLNs of GIARS mice were mostly CCL1+IL-10+LIGHT+miR-27a+ Mϕ (M2bMϕ, inhibitor cells for the M1Mϕ polarization). Reduced long noncoding RNA Gas5 and increased miR-222 expression in MLN-Mϕ influenced by the irradiation were shown to be associated with M2bMϕ polarization. In this study, the mortality of mice exposed to 7 Gy of γ-rays (7 Gy GIARS mice) was completely controlled after the administration of glycyrrhizin (GL), a major active ingredient in licorice root (Glycyrrhiza glabra). Bacterial translocation and subsequent sepsis were minimal in 7 Gy GIARS mice treated with GL. Increased Gas5 RNA level and decreased miR-222 expression were shown in MLN-Mϕ isolated from 7 Gy GIARS mice treated with GL, and these macrophages did not display any properties of M2bMϕ. These results indicate that gut bacteria-associated sepsis in 7 Gy GIARS mice was controlled by the GL through the inhibition of M2bMϕ polarization at the bacteria translocation site. Expression of Ccl1, a gene required for M2bMϕ survival, is silenced in the MLNs of 7 Gy GIARS mice because of Gas5 RNA, which is increased in these cells after the suppression of miR-222 (a Gas5 RNA expression inhibitor) by the GL.


Assuntos
Bactérias/imunologia , Infecções Bacterianas , Fenômenos Fisiológicos Bacterianos , Translocação Bacteriana , Raios gama/efeitos adversos , Ácido Glicirrízico/farmacologia , Intestinos , Macrófagos , MicroRNAs/imunologia , RNA Longo não Codificante/imunologia , Lesões Experimentais por Radiação , Animais , Infecções Bacterianas/imunologia , Infecções Bacterianas/patologia , Infecções Bacterianas/prevenção & controle , Fenômenos Fisiológicos Bacterianos/efeitos dos fármacos , Fenômenos Fisiológicos Bacterianos/imunologia , Fenômenos Fisiológicos Bacterianos/efeitos da radiação , Translocação Bacteriana/efeitos dos fármacos , Translocação Bacteriana/imunologia , Translocação Bacteriana/efeitos da radiação , Intestinos/imunologia , Intestinos/microbiologia , Macrófagos/imunologia , Macrófagos/microbiologia , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Lesões Experimentais por Radiação/imunologia , Lesões Experimentais por Radiação/microbiologia , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/prevenção & controle , Sepse/imunologia , Sepse/microbiologia , Sepse/patologia , Sepse/prevenção & controle
18.
Genes (Basel) ; 11(1)2020 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-31947954

RESUMO

PURPOSE: Ionizing radiation induced foci (IRIF) known also as DNA repair foci represent most sensitive endpoint for assessing DNA double strand breaks (DSB). IRIF are usually visualized and enumerated with the aid of fluorescence microscopy using antibodies to γH2AX and 53BP1. This study analyzed effect of low dose ionizing radiation on residual IRIF in human lymphocytes to the aim of potential biodosimetry and possible extrapolation of high-dose γH2AX/53BP1 effects to low doses and compared kinetics of DSB and IRIF. We also analyzed whether DNaseI, which is used for reducing of clumps, affects the IRIF level. MATERIALS AND METHODS: The cryopreserved human lymphocytes from umbilical cord blood (UCB) were thawed with/without DNaseI, γ-irradiated at doses of 0, 5, 10, and 50 cGy and γH2AX/53BP1 foci were analyzed 30 min, 2 h, and 22 h post-irradiation using appropriate antibodies. We also analyzed kinetics of DSB using PFGE. RESULTS: No significant difference was observed between data obtained by γH2AX foci evaluation in cells that were irradiated by low doses and data obtained by extrapolation from higher doses. Residual 53BP1 foci induced by low doses significantly outreached the data extrapolated from irradiation by higher doses. 53BP1 foci induced by low dose-radiation remain longer at DSB loci than foci induced by higher doses. There was no significant effect of DNaseI on DNA repair foci. CONCLUSIONS: Primary γH2AX, 53BP1 foci and their co-localization represent valuable markers for biodosimetry of low doses, but their usefulness is limited by short time window. Residual γH2AX and 53BP1 foci are more useful markers for biodosimetry in vitro. Effects of low doses can be extrapolated from high dose using γH2AX residual foci while γH2AX/53BP1 foci are valuable markers for evaluation of initial DSB induced by ionizing radiation. Residual IRIF induced by low doses persist longer time than those induced by higher doses.


Assuntos
Reparo do DNA , Raios gama/efeitos adversos , Linfócitos/metabolismo , Relação Dose-Resposta à Radiação , Histonas/metabolismo , Humanos , Linfócitos/patologia , Microscopia de Fluorescência , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo
19.
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
20.
Probl Radiac Med Radiobiol ; 24: 411-425, 2019 Dec.
Artigo em Inglês, Ucraniano | MEDLINE | ID: mdl-31841483

RESUMO

OBJECTIVE: to estimate the chromosome type aberrations outcome in lung cancer patients during radiation therapy course depending on radiation energy. MATERIALS AND METHODS: Chromosome aberrations were studied in 16 lung cancer patients examined before treat- ment in the middle and at the end of external gamma-radiotherapy 60Со on ROCUS-AM and megavolt therapy on lin- ear accelerator Clinac 600C. RESULTS: The radiation-induced chromosome aberrations outcome in lung cancer patients during radiotherapy with different irradiation sources was studied. The over-spontaneous excess of chromosome type aberrations in cancer patients before treatment was shown. The similar and different features of cytogenetic damage accumulation dur- ing radiation therapy regarding to radiation type was displayed. The cytogenetic damage frequency raised during the course of therapeutic exposure in both studied groups. At the same time, the growth rate depended on the irra- diation regimen and was higher for patients undergoing 60Co gamma-therapy. The different range of cells with unsta- ble chromosome aberrations from the beginning to the end of the radiation therapy course was displayed. In the middle of the course the number of aberrations per aberrant cell was similar - 1-5 damages for gamma therapy, 1-4 damages for megavoltage therapy. At the end of treatment the maximum of 10 aberrations per aberrant cell for ROCUS-AM and in 5 aberrations per aberrant cell for linear accelerator was observed. During radiotherapy the distri- butions of radiation-induced chromosome aberrations was found to be over-dispersed according to Poisson statis- tic in both patients' groups. CONCLUSIONS: The study of chromosome type aberration revealed the particularities of cytogenetic damages out- come during radiotherapy course depending on the irradiation source used. The more pronounced genotoxic effect in blood lymphocytes of lung cancer patients due to gamma-irradiation with ROCUS-AM was demonstra- ted despite the higher radiation energy used on a linear accelerator. Therefore, in radiation treatment effects estimation it is necessary to take into account not only the radiation quality and energy, but also the source, regimen and pre-radiotherapy procedures. The data obtained can contribute to the assessment of the conse- quences of local fractionated irradiation and to the development of a reference biodosimetry system in radia- tion therapy.


Assuntos
Aberrações Cromossômicas/efeitos da radiação , Raios gama/efeitos adversos , Neoplasias Pulmonares/radioterapia , Linfócitos/efeitos da radiação , Idoso , Estudos de Casos e Controles , Análise Citogenética , Dano ao DNA , Relação Dose-Resposta à Radiação , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Doses de Radiação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA