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1.
Radiat Res ; 198(6): 599-614, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36279323

RESUMO

Well-characterized and validated animal models are required for the development of medical countermeasures (MCMs) for acute radiation syndrome to mitigate injury due to high doses of total- or partial-body irradiation. Animal models used in MCM development must reflect a radiation dose- and time-dependent relationship, clinical presentation, and pathogenesis of organ injuries in humans. The objective of the current study was to develop the lethality curve for the Armed Forces Radiobiology Research Institute high level cobalt-60 gamma-radiation source in nonhuman primates (NHPs) after total-body irradiation. A dose-response relationship was determined using NHPs (rhesus macaques, N = 36, N = 6/radiation dose) irradiated with 6 doses in the range of 6.0 to 8.5 Gy, with 0.5 Gy increments at a dose rate of 0.6 Gy/min. Animals were provided subject-based supportive care including blood transfusions and were monitored for 60 days postirradiation. Survival was the primary endpoint of the study and the secondary endpoint included hematopoietic recovery. The lethality curve suggested LD30/60, LD50/60, and LD70/60 values as 5.71, 6.78, and 7.84 Gy, respectively. The results of this study will be valuable to provide specific doses for various lethalities of 60Co-gamma radiation to test radiation countermeasures in rhesus macaques using subject-based supportive care including blood transfusion.


Assuntos
Radioisótopos de Cobalto , Raios gama , Exposição à Radiação , Animais , Raios gama/efeitos adversos , Macaca mulatta , Radiobiologia , Exposição à Radiação/efeitos adversos , Radioisótopos de Cobalto/efeitos adversos
2.
PLoS One ; 16(3): e0231511, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33657093

RESUMO

The Department of Energy conduced ten large-scale neutron irradiation experiments at Argonne National Laboratory between 1972 and 1989. Using a new approach to utilize experimental controls to determine whether a cross comparison between experiments was appropriate, we amalgamated data on neutron exposures to discover that fractionation significantly improved overall survival. A more detailed investigation showed that fractionation only had a significant impact on the death hazard for animals that died from solid tumors, but did not significantly impact any other causes of death. Additionally, we compared the effects of sex, age first irradiated, and radiation fractionation on neutron irradiated mice versus cobalt 60 gamma irradiated mice and found that solid tumors were the most common cause of death in neutron irradiated mice, while lymphomas were the dominant cause of death in gamma irradiated mice. Most animals in this study were irradiated before 150 days of age but a subset of mice was first exposed to gamma or neutron irradiation over 500 days of age. Advanced age played a significant role in decreasing the death hazard for neutron irradiated mice, but not for gamma irradiated mice. Mice that were 500 days old before their first exposures to neutrons began dying later than both sham irradiated or gamma irradiated mice.


Assuntos
Radioisótopos de Cobalto/efeitos adversos , Raios gama/efeitos adversos , Neoplasias Induzidas por Radiação/etiologia , Nêutrons/efeitos adversos , Animais , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Camundongos
3.
Sci Rep ; 11(1): 89, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420217

RESUMO

Current models to study the hematopoietic syndrome largely rely on the uniform whole-body exposures. However, in the radio-nuclear accidents or terrorist events, exposure can be non-uniform. The data available on the non-uniform exposures is limited. Thus, we have developed a mice model for studying the hematopoietic syndrome in the non-uniform or partial body exposure scenarios using the localized cobalt60 gamma radiation exposure. Femur region of Strain 'A' male mice was exposed to doses ranging from 7 to 20 Gy. The 30 day survival assay showed 19 Gy as LD100 and 17 Gy as LD50. We measured an array of cytokines and important stem cell markers such as IFN-γ, IL-3, IL-6, GM-CSF, TNF-α, G-CSF, IL-1α, IL-1ß, CD 34 and Sca 1. We found significant changes in IL-6, GM-CSF, TNF-α, G-CSF, and IL-1ß levels compared to untreated groups and amplified levels of CD 34 and Sca 1 positive population in the irradiated mice compared to the untreated controls. Overall, we have developed a mouse model of the hematopoietic acute radiation syndrome that might be useful for understanding of the non-uniform body exposure scenarios. This may also be helpful in the screening of drugs intended for individuals suffering from radiation induced hematopoietic syndrome.


Assuntos
Síndrome Aguda da Radiação/etiologia , Modelos Animais de Doenças , Doenças Hematológicas/etiologia , Exposição à Radiação/efeitos adversos , Síndrome Aguda da Radiação/genética , Síndrome Aguda da Radiação/metabolismo , Animais , Radioisótopos de Cobalto/efeitos adversos , Radioisótopos de Cobalto/química , Citocinas/genética , Citocinas/metabolismo , Fêmur/metabolismo , Fêmur/efeitos da radiação , Raios gama/efeitos adversos , Doenças Hematológicas/genética , Doenças Hematológicas/metabolismo , Humanos , Masculino , Camundongos
4.
Int J Radiat Biol ; 96(10): 1309-1316, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32659144

RESUMO

PURPOSE: The novelty in flower color or inflorescence form is recognized as a valuable trait in Chrysanthemum - a potential commercial flower crop with significant worth in global cut flower trade. This study was conducted to irradiate white and orange flowered cultivars of Chrysanthemum with an objective to identify and isolate desirable types representing novelty in flower color and inflorescence form from the irradiated populations. The terminal rooted cuttings of Chrysanthemum exposed to γ-irradiation at 10 or 15 Gy doses were found effective for inducing novel flower color variants in cultivars Thiching Queen and Purnima. The mutant progeny evolved with novel inflorescence traits of these cultivars will enrich the existing germplasm of Chrysanthemum for further utilization in breeding programs. MATERIALS AND METHODS: Two standard type Chrysanthemum cultivars, Thiching Queen and Purnima were exposed to varied doses of γ-rays (0, 5, 10, 15, and 20 Gy) using Cobalt 60 (60Co) as irradiation source for treating rooted cuttings. The irradiated mutant population was evaluated for likely variation in various vegetative and flowering characters compared to non-irradiated (control) plants. RESULTS: In Chrysanthemum cultivars Thiching Queen, seven and 'in Purnima', two flower color variants were isolated from the irradiated populations that were reportedly novel in color and desirable for commercial aspect. The leaf abnormalities were observed in mutant populations exhibiting variation in flower color, shape, and size of leaves. Certain floral abnormalities were also observed in inflorescence that reportedly progressed with increase in dosage of γ-rays irradiation. CONCLUSIONS: This study developed a gamma ray (60Co) induced mutagenesis protocol with potential application to develop novel and desirable mutants in Chrysanthemum.


Assuntos
Chrysanthemum/efeitos da radiação , Radioisótopos de Cobalto/efeitos adversos , Raios gama/efeitos adversos , Inflorescência/efeitos da radiação , Chrysanthemum/crescimento & desenvolvimento , Chrysanthemum/metabolismo , Relação Dose-Resposta à Radiação , Inflorescência/crescimento & desenvolvimento , Inflorescência/metabolismo , Dose Letal Mediana , Pigmentação/efeitos da radiação
5.
Health Phys ; 119(1): 52-58, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32483043

RESUMO

The objective of this study was to establish radiation dose-response calibration curves using automated dicentric scoring to support rapid and accurate cytogenetic triage dose-assessment. Blood was drawn from healthy human volunteers and exposed to Co gamma rays at several dose rates (i.e., 1.0, 0.6, and 0.1 Gy min). After radiation, the blood was placed for 2 h in a 37 °C incubator for repair. Blood was then cultured in complete media to which a mitogen (i.e., phytoghemagglutinin, concentration 4%) was added for 48 h. Colcemid was added to the culture at a final concentration of 0.2 µg mL after 24 h for the purpose of arresting first-division metaphase mitotics. Cells were harvested at the end of 48 h. Samples were processed using an automated metaphase harvester and automated microscope metaphase finder equipped with a suite of software including a specialized automated dicentric scoring application. The data obtained were used to create dose-response tables of dicentric yields. The null hypothesis that the data is Poisson-distributed could not be rejected at the significance level of α = 0.05 using results from a Shiny R Studio application (goodness-of-fit Poisson). Calibration curves based on linear-quadratic fits for Co gamma rays at the three different dose rates were generated using these data. The calibration curves were used to detect blind test cases. In conclusion, using the automated harvester and automated microscope metaphase finder with associated automated dicentric scoring software demonstrates high-throughput with suitable accuracy for triage radiation dose assessment.


Assuntos
Radioisótopos de Cobalto/efeitos adversos , Raios gama/efeitos adversos , Exposição à Radiação/efeitos adversos , Triagem/métodos , Automação , Sangue/efeitos da radiação , Células Sanguíneas/efeitos da radiação , Calibragem , Aberrações Cromossômicas , Demecolcina/química , Relação Dose-Resposta à Radiação , Humanos , Mitógenos/química , Distribuição de Poisson , Doses de Radiação , Proteção Radiológica , Radiometria , Software , Fatores de Tempo
6.
Health Phys ; 119(3): 297-305, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32384371

RESUMO

There is increasing evidence that the expression of non-coding RNA and mRNA (messenger RNA) is significantly altered following high-dose ionizing radiation (IR), and their expression may play a critical role in cellular responses to IR. However, the role of non-coding RNA and mRNA in radiation protection, especially in the nervous system, remains unknown. In this study, microarray profiles were used to determine microRNA (miRNA), long non-coding RNA (lncRNA), and mRNA expression in the hypothalamus of mice that were pretreated with amifostine and subsequently exposed to high-dose IR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. We found that fewer miRNAs, lncRNAs, and mRNAs were induced by amifostine pre-treatment in exposed mice, which exhibited antagonistic effects compared to IR, indicating that amifostine attenuated the IR-induced effects on RNA profiles. GO and KEGG pathway analyses showed changes in a variety of signaling pathways involved in inflammatory responses during radioprotection following amifostine pre-treatment in exposed mice. Taken together, our study revealed that amifostine treatment altered or attenuated miRNA, lncRNA, and mRNA expression in the hypothalamus of exposed mice. These data provide a resource to further elucidate the mechanisms underlying amifostine-mediated radioprotection in the hypothalamus.


Assuntos
Amifostina/farmacologia , Radioisótopos de Cobalto/efeitos adversos , Raios gama/efeitos adversos , Hipotálamo/efeitos da radiação , MicroRNAs/efeitos da radiação , RNA Longo não Codificante/efeitos da radiação , RNA Mensageiro/efeitos da radiação , Protetores contra Radiação/farmacologia , Transcriptoma/efeitos da radiação , Animais , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Análise de Sequência com Séries de Oligonucleotídeos , Irradiação Corporal Total/efeitos adversos
7.
Health Phys ; 119(3): 351-357, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31934930

RESUMO

Studies performed decades ago in the canine and nonhuman primate established the dose response relationships for the hematopoietic acute radiation syndrome in response to mixed neutron/gamma, x-radiation, and Co gamma radiation. There were no published studies that determined the dose response relationships for the gastrointestinal acute radiation syndrome in response to either noted radiation quality. This analysis of a retrospective, unpublished study provided the dose response relationships in a canine model for the acute gastrointestinal syndrome relative to the acute hematopoietic syndrome due to mixed neutron/gamma radiation. Canines were exposed to total-body, steady state, bilateral, 0.40 Gy min, mixed neutron/gamma (5.4:1) radiation from a TRIGA reactor. The average neutron/gamma energy (MeV) was 0.85/0.9, and exposure was reported as midline tissue dose. Medical management was not administered. The mixed neutron/gamma exposure resulted in an estimated LD50/6 of 2.83 Gy [2.76, 2.94] and LD50/30 of 2.16 Gy [2.01, 2.24] for the GI- and H-ARS respectively. The mean survival times for decedents after mixed neutron/gamma exposure approximate to the LD50/6 were 8.5 d, 10.5 d, and 4 d for 2.75 Gy, 2.80 Gy, 3.00, and 3.12 Gy exposures, respectively. The mean survival times for decedents for mixed neutron/gamma exposure approximate to the LD50/30 were 21.3 d and 15.6 d for 2.00 Gy and 2.25 Gy, respectively. Furthermore, the dose response relationships for the acute hematopoietic syndrome due to mixed neutron/gamma exposure (0.85/0.9 MeV; 5.4:1) resulted in an estimated relative biological effectiveness of 1.2 as compared with reference Co gamma radiation.


Assuntos
Síndrome Aguda da Radiação/etiologia , Radioisótopos de Cobalto/efeitos adversos , Raios gama/efeitos adversos , Síndrome Aguda da Radiação/mortalidade , Animais , Radioisótopos de Cobalto/administração & dosagem , Modelos Animais de Doenças , Cães , Relação Dose-Resposta à Radiação , Feminino , Masculino , Lesões Experimentais por Radiação/etiologia , Estudos Retrospectivos , Irradiação Corporal Total/efeitos adversos , Irradiação Corporal Total/mortalidade
8.
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
9.
Phys Med ; 62: 13-19, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31153393

RESUMO

PURPOSE: The present work aimed to evaluate organ doses and related risk for cancer from external beam radiation treatment (EBRT) and high-dose-rate (HDR) brachytherapy (BT) involving Co-60 source for patients with cervical carcinoma in Tanzania based on Monte Carlo methods and to evaluate the secondary cancer risks in their lifetime. METHODS: EBRT and HDR-BR were modelled by using the MCNPX Monte Carlo (MC) code. The MC simulations were performed by using validated models and isocentric irradiation of an adult female computational phantom. The organ doses and cancer risks estimates were obtained. RESULTS: The highest absorbed doses of 6.98 × 10-2 and 5.74 × 10-2 Sv/Gy were recorded in the bladder for BT and EBRT. The higher risk was found for colon at 1.06 × 10-3 in the HDR-BT and 9.75 × 10-5 in the EBRT per 100,000 population at exposure age of 35 years than in the other organs. The risk magnitude decreased with increasing age at exposure. In general, the secondary cancer risks in all sites considered from EBRT and HDR-BR for cervical cancer patient were lower than the baseline risks. CONCLUSIONS: The chances of developing secondary cancer take years following radiation therapy are extremely low, but the results of present study can support to establish a future database on secondary cancer risks involving radiation therapy in patients with cervical cancer by using HDR-BR and EBRT with Co-60 source in Tanzania and other developing countries.


Assuntos
Radioisótopos de Cobalto/efeitos adversos , Método de Monte Carlo , Neoplasias Induzidas por Radiação/etiologia , Fótons/efeitos adversos , Doses de Radiação , Espalhamento de Radiação , Neoplasias do Colo do Útero/radioterapia , Braquiterapia/efeitos adversos , Radioisótopos de Cobalto/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Segunda Neoplasia Primária/etiologia , Órgãos em Risco/efeitos da radiação , Fótons/uso terapêutico , Dosagem Radioterapêutica , Risco , Tanzânia
10.
Int J Radiat Biol ; 95(9): 1259-1267, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31140905

RESUMO

Purpose: This study aimed to construct a calibration curve for high-dose exposure using cell fusion-induced premature chromosome condensation (PCC). Some of the associated practicalities and methodological details were also investigated. Materials and methods: Peripheral blood from two donors was used. PCC mediated by fusing mitotic CHO cells with interphase lymphocytes was carried out. Lymphocytes were irradiated with 60Co (0-20 Gy) and held at 37 °C for 24 h post exposure. Results: The protocol for PCC induction was effective at all doses and the number of rings increased with increasing dose. No significant difference was found between the donors (p = .896) and data were pooled. Ring aberration frequencies followed a Poisson distribution and the dose-response relationship favored a linear fitting: Y = 0.0007(±0.0004)+0.0186(±0.001)×D. Blind tests showed that the estimated doses were all within the 95% confidence limits of the delivered doses. This study has shown that it is valid to score only 100 cells per sample in a triage mode for doses above 5 Gy and that it is valid to score only hollow rings to reduce the scoring time. Conclusion: Scoring rings in cell fusion-induced PCC assay can be a feasible and fast approach for the analysis of high-dose exposures.


Assuntos
Aberrações Cromossômicas/efeitos da radiação , Raios gama/efeitos adversos , Animais , Células CHO , Calibragem , Fusão Celular , Radioisótopos de Cobalto/efeitos adversos , Cricetulus , Relação Dose-Resposta à Radiação , Linfócitos/metabolismo , Linfócitos/efeitos da radiação
11.
Int J Biol Macromol ; 135: 887-897, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31132438

RESUMO

Radiation is known to be associated with pathology of various human diseases. This study has focused on the effect of radiation on glucose homeostasis with regard to metabolic function of liver and pancreas and the effect of polysaccharide from the fruiting bodies of Auricularia auricular (SNAAP) on glucose metabolism. The 60Co-γ-radiated mice displayed destroyed redox equilibrium, accompanied by increased blood glucose accumulation, decreased insulin and hepatic glycogen contents, impaired blood glucose tolerance ability, abnormal changes in activities of glucose metabolism-related enzymes and damaged hepatic and pancreatic function, while SNAAP can restore the disordered glucose metabolism to some extent. Increased phosphorylation of JNK and FoxO1, reduced phosphorylation of Akt and GSK-3ß and increased expression of PEPCK, G6Pase and GYS2 in the liver as well as the decreased expression of PDX1, GLUT2 and IRS1 in the pancreas of radiated mice were recovered after treated with SNAAP, leading to an improved gluconeogenesis and glycogen synthesis. These findings clearly indicate that SNAAP has significant potency in radiation-induced glucose metabolism disorder through modulating the JNK pathway in the liver as well as the PDX1/GLUT2 in the pancreas.


Assuntos
Basidiomycota/química , Glicemia/metabolismo , Radioisótopos de Cobalto/efeitos adversos , Carpóforos/química , Polissacarídeos Fúngicos/farmacologia , Animais , Antioxidantes/metabolismo , Peso Corporal/efeitos dos fármacos , Peso Corporal/efeitos da radiação , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Líquidos/efeitos da radiação , Jejum/sangue , Proteína Forkhead Box O1/metabolismo , Glicogênio/metabolismo , Insulina/sangue , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos da radiação , Masculino , Camundongos , Fosforilação/efeitos dos fármacos , Fosforilação/efeitos da radiação , Proteínas Proto-Oncogênicas c-akt/metabolismo
12.
Int J Radiat Biol ; 95(6): 753-763, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30822214

RESUMO

Purpose: The effect of low level cobalt-60 (60Co) gamma radiation on the freshwater prawn Macrobrachium rosenbergii was evaluated by observing their hemocyte counts and biochemical parameters. Materials and methods: Prawns were exposed to 3, 30, 300 and 3000 milligray (mGy) dose levels and their tissues of gills, hepatopancreas and muscle were analyzed. Results: The results showed that the number of hemocytes in the hemolymph and concentrations of protein and carbohydrate were significantly reduced in irradiated groups than compared to the control prawn. Increased aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), Acetyl choline esterase (AChE) in the irradiated groups reflects tissue damage. Conclusions: Hence, this study concludes that even low level of ionizing radiation (60Co gamma) can cause acute damages in gills, hepatopancreas and muscles in irradiated groups. Highlights 60Co exposures effect the THC and biochemical of prawn M. rosenbergii. Different dose levels such as 3, 30, 300 and 3000 mGy. Biochemical parameters serve as reliable indicators of physical status of organism. Self-regulating mechanisms might be the reason for preventing from the lethality. Suggested that nuclear industries should manage below 3 mGy.


Assuntos
Radioisótopos de Cobalto/efeitos adversos , Raios gama/efeitos adversos , Hemócitos/citologia , Hemócitos/efeitos da radiação , Palaemonidae/efeitos da radiação , Animais , Metabolismo dos Carboidratos/efeitos da radiação , Contagem de Células , Palaemonidae/citologia , Palaemonidae/metabolismo
13.
Int J Radiat Biol ; 95(3): 307-313, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30481092

RESUMO

PURPOSE: The purposes of this study are to investigate spontaneous dicentric frequencies and dose-response curves of dicentrics induced by gamma 60Co for replenishing the data sets used for biodosimetry in Vietnam. MATERIALS AND METHODS: One hundred and four healthy donor blood samples were collected for chromosome aberrations background study, 03 healthy donor blood samples were used for generating the dose-response curves at 1.96 mGy/min and 275 mGy/min. Blood collection, in vitro irradiation, cell culture and harvest, slide preparation and metaphase scoring were performed according to IAEA standard protocol (2011). Blind exposed samples were scored for verifying each curve. RESULTS: The dicentric, fragment and chromatid break frequencies in 106,310 metaphases of 104 donors were 0.023% ± 0.005%, 0.045% ± 0.007% and 0.101% ± 0.011%, respectively. The dose-response curve for low-dose rate was y = C + (0.0137 ± 0.0055)D + (0.0912 ± 0.0142)D2 and for high-dose rate was y = C + (0.0337 ± 0.0046)D + (0.0539 ± 0.0031)D2, where both of them were verified. CONCLUSION: The data of this study were established for biological dose assessment in cases with low LET of accidental or occupational radiation exposures in the dose range of 0.1-5.0 Gy.


Assuntos
Aberrações Cromossômicas/efeitos da radiação , Radioisótopos de Cobalto/efeitos adversos , Análise Citogenética , Raios gama/efeitos adversos , Linfócitos/metabolismo , Linfócitos/efeitos da radiação , Radiometria/métodos , Adulto , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vietnã
14.
J Cancer Res Ther ; 14(Supplement): S1098-S1104, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30539852

RESUMO

INTRODUCTION: Skin is highly prone to radiation damage. Radiation burn is defined as damage to the skin or other biological tissues induced by radiofrequency or ionizing radiation. Vascular endothelial growth factor (VEGF) is a heparin-binded pro-angiogenic factor. Flavonoids belong to a family of polyphenol chemical compounds that are frequently present in fruits and vegetables. Hesperidin is an agent belonging to the flavonoid family. The aim of this study is to investigate whether hesperidin can affect the VEGF gene expression in rat skin following gamma irradiation or not. MATERIALS AND METHODS: A total number of 36 male Sprague-Dawley rats were divided into three groups. First group: radiation group (n = 12), second group: radiation + hesperidin-treated group (n = 12), and third group: untreated control group (n = 12). The hesperidin administration dose was 100 mg/kg body weight. The rats received a 22 Gy single dose at a dose rate of about 0.3 Gy/min using a cobalt-60 external beam radiotherapy unit. The animals were euthanized 24 h postirradiation. VEGF gene expression data were analyzed using the equation 2-ΔΔCT, where ΔΔCT = (Threshold cycle [CT], of target gene - CT of housekeeping gene)treated group- (CT of target gene - CT of housekeeping gene)untreated control group. Glyceraldehyde-3-phosphate dehydrogenase gene was used as a housekeeping gene. RESULTS: VEGF gene in the radiation + hesperidin group overexpressed 25-fold relative to the control group. In addition, VEGF gene in the radiation group underexpressed 0.15-fold relative to the control group. When the three groups were compared relative to each other using the Kruskal-Wallis test, P < 0.001 was obtained. Based on the Mann-Whitney U-test, when all groups were compared to each in a binary model, P = 0.001 was achieved. These tests all showed statistically significant changes in VEGF gene expression. CONCLUSIONS: We can conclude that hesperidin is a potent angiogenic factor. Hesperidin as a radioprotector can initiate angiogenesis by VEGF gene induction. It may stimulate epithelialization, collagen deposition, and enhanced cellular proliferation. These changes can together accelerate wound healing, in particular, radiation-induced skin damage.


Assuntos
Queimaduras/prevenção & controle , Hesperidina/farmacologia , Lesões Experimentais por Radiação/prevenção & controle , Protetores contra Radiação/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Administração Oral , Animais , Queimaduras/etiologia , Queimaduras/patologia , Radioisótopos de Cobalto/efeitos adversos , Raios gama/efeitos adversos , Hesperidina/uso terapêutico , Masculino , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/efeitos da radiação , Lesões Experimentais por Radiação/patologia , Protetores contra Radiação/uso terapêutico , Ratos , Ratos Sprague-Dawley , Pele/irrigação sanguínea , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Resultado do Tratamento
15.
J Gynecol Oncol ; 29(5): e86, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30049023

RESUMO

OBJECTIVE: To determine and compare treatment outcomes between cobalt-60 (Co-60) and iridium-192 (Ir-192) high dose rate (HDR) brachytherapy in stage IB2-IIIB cervical cancer patients at Department of Radiology, Faculty of Medicine Vajira Hospital, Navamindrahiraj University. METHODS: A retrospective cohort study of patients diagnosed with cervical cancer and treated with radiotherapy at the Department of Radiation Oncology, Faculty of Medicine Vajira Hospital between 2004 and 2014. Survival rate was analyzed by Kaplan-Meier method and were compared between groups with log-rank test. Multivariate analysis was performed using Cox proportional hazards model. RESULTS: A total of 480 patients with cervical cancer and treated with radiotherapy were included, 274 patients for Ir-192 group and 206 patients for Co-60 group. The 2- and 5-year disease-free survival rate in Ir-192 group were 80.4% and 73.1% and in Co-60 group were 82.5% and 74.7%, respectively (p=0.365). Overall survival rates at 2 and 5 years were 89.4% and 77% of the Ir-192 group, and 91.6% and 81.9% in the Co-60 group, respectively (p=0.238). The complications were primarily grade 1 or 2. Grade 3 and 4 complications were found in 13 of 274 and 7 of 206 in Ir-192 and Co-60 groups, respectively (p=0.232). Grade and clinical stage of cancer significantly affected the survival outcome. CONCLUSION: Cervical cancer patients who were treated with HDR Co-60 brachytherapy were comparable in survival and toxicity outcomes of those with HDR Ir-192 brachytherapy. Co-60 source has lots of economic advantages over Ir-192 and hence suitable for low resource radiotherapy setting.


Assuntos
Braquiterapia/métodos , Radioisótopos de Cobalto/uso terapêutico , Radioisótopos de Irídio/uso terapêutico , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/efeitos adversos , Radioisótopos de Cobalto/efeitos adversos , Feminino , Humanos , Radioisótopos de Irídio/efeitos adversos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Adulto Jovem
16.
Molecules ; 23(6)2018 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-29890658

RESUMO

A novel chitosan microsphere for encapsulating pine cone polyphenols (PP) from P. koraiensis was successfully prepared using an emulsion crosslinking technique. The characteristics of pine polyphenol-loaded microspheres (PPM) were determined using scanning electron microscopy (SEM) and a laser particle size detector. It was found that PPMs were spherical in shape with uniform particle size distribution patterns. The drug content and encapsulation rate of the microspheres were 7.47% and 73.6%, respectively, at a Ch/GA mass ratio of 0.7. The animal experiments showed that PPM had a stronger radiation protective effect than PP. PPM significantly increased the immune organ indices, the quantity of marrow DNA, the superoxide dismutase (SOD) activity, the splenocyte proliferation index, and the phagocytosis activity of monocytes. PPM also decreased the numbers of micronuclei in bone marrow cells and malondialdehyde (MDA) levels in plasma in mice exposed to 60Co γ-irradiation. In addition, gender differences in biological responses to exposure to radiation were observed.


Assuntos
Quitosana/química , Radioisótopos de Cobalto/efeitos adversos , Microesferas , Pinus/química , Polifenóis/farmacologia , Lesões por Radiação/prevenção & controle , Protetores contra Radiação/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Dano ao DNA , Feminino , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos ICR , Microscopia Eletrônica de Varredura , Fagocitose/efeitos dos fármacos , Polifenóis/administração & dosagem , Protetores contra Radiação/administração & dosagem , Baço/efeitos dos fármacos , Superóxido Dismutase/metabolismo
17.
Brachytherapy ; 17(5): 768-774, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29895451

RESUMO

PURPOSE: Second primary malignancies (SPMs) may occur in organs after radiotherapy (RT). This study aimed to determine the rate and distribution of SPMs for photon- or neutron-emitting radiotherapy sources for patients treated for primary endometrial cancer. METHODS AND MATERIALS: The cohort comprised 426 patients with 5334 patient-years of observation. Patients were treated by different methods of RT from 1990 to 2000. Patients received postoperative 60Co external-beam radiotherapy (43.4%), external-beam radiotherapy + high-dose-rate (HDR) intracavitary brachytherapy with 60Co or 252Cf (42.3%), or HDR intracavitary brachytherapy alone with 60Co or 252Cf (14.3%). RESULTS: Over a 25-year period, 47 SPMs were observed (21 for HDR 60Co and 26 for HDR 252Cf). SPMs were observed for 13 patients in the high-intermediate risk group for each radiation source. Patients treated with 60Co developed SPMs in the urinary tract (1.2%) and in lymphoid/hematopoietic tissues (1.2%). Only three SPM cases (0.7%) were observed in digestive tract. In comparison, the patient group treated with 252Cf developed SPMs in the digestive tract (1.4%) with the majority in the colon (1.2%), urinary tract (0.9%) primarily the kidneys, and vulva (0.7%). All other SPMs (4.9%) were in the low-risk group. Of these, SPMs in the skin were most prevalent (1.6%) for 60Co, and breast (1.6%) for 252Cf, but believed to be caused by factors other than treatment. SPM incidence in the digestive and urinary tracts were similar (2.1%), regardless of radiation source. CONCLUSIONS: For followup at 25 years, 47 SPMs were observed with no differences in the high-intermediate risk group depending on the RT source.


Assuntos
Califórnio/efeitos adversos , Radioisótopos de Cobalto/efeitos adversos , Neoplasias do Endométrio/radioterapia , Segunda Neoplasia Primária/etiologia , Nêutrons/uso terapêutico , Adulto , Idoso , Braquiterapia/métodos , Protocolos Clínicos , Neoplasias do Endométrio/diagnóstico , Feminino , Seguimentos , Humanos , Incidência , Lituânia/epidemiologia , Pessoa de Meia-Idade , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/epidemiologia , Dosagem Radioterapêutica
18.
Radiat Environ Biophys ; 57(3): 215-222, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29774413

RESUMO

Chromosome damage is related to DNA damage and erroneous repair. It can cause cell dysfunction and ultimately induce carcinogenesis. Histone acetylation is crucial for regulating chromatin structure and DNA damage repair. Ionizing radiation (IR) can alter histone acetylation. However, variations in histone acetylation in response to IR exposure and the relationship between histone acetylation and IR-induced chromosome damage remains unclear. Hence, this study investigated the variation in the total acetylation levels of H3 and H4 in human lymphocytes exposed to 0-2 Gy 60Co γ-rays. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, was added to modify the histone acetylation state of irradiated cells. Then, the total acetylation level, enzyme activity, dicentric plus centric rings (dic + r) frequencies, and micronucleus (MN) frequencies of the treated cells were analyzed. Results indicated that the acetylation levels of H3 and H4 significantly decreased at 1 and 24 h, respectively, after radiation exposure. The acetylation levels of H3 and H4 in irradiated groups treated with SAHA were significantly higher than those in irradiated groups that were not treated with SAHA. SAHA treatment inhibited HDAC activity in cells exposed to 0-1 Gy 60Co γ-rays. SAHA treatment significantly decreased dic + r/cell and MN/cell in cells exposed to 0.5 or 1.0 Gy 60Co γ-rays relative to that in cells that did not receive SAHA treatment. In conclusion, histone acetylation is significantly affected by IR and is involved in chromosome damage induced by 60Co γ-radiation.


Assuntos
Cromossomos Humanos/genética , Radioisótopos de Cobalto/efeitos adversos , Raios gama/efeitos adversos , Histonas/metabolismo , Linfócitos/efeitos da radiação , Acetilação/efeitos dos fármacos , Acetilação/efeitos da radiação , Linhagem Celular , Inibidores de Histona Desacetilases/farmacologia , Humanos , Ácidos Hidroxâmicos/farmacologia , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Vorinostat
19.
Molecules ; 23(5)2018 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-29701645

RESUMO

The diamondback moth, Plutella xylostella (Linnaeus), is one of the notorious pests causing substantial loses to many cruciferous vegetables across the nations. The effects of 60Co-γ radiation on physiology of P. xylostella were investigated and the results displayed that 200 Gy irradiation significantly alters the antioxidant enzyme regulation in six-day-old male pupae of P. xylostella. First, in our research, we detected Oxidase system and stress response mechanism of irradiated pupae, the results displayed that 200 Gy irradiation significantly alters the antioxidant enzyme regulation in six-day-old male pupae of P. xylostella. The levels of superoxide dismutase (SOD) and catalase (CAT) were increased significantly in contrast the level of peroxidase (POD) and glutathione S-transferase (GST) were decreased in 12⁻24 h post-treatment. The heat shock proteins (Hsps) gene expression level was significant increasing, maximum > 2-folds upregulation of genes were observed in peak. However, they also had a trend of gradual recovery with development. Second, we detected the testis lactate dehydrogenase (LDH) and acid phosphatase (ACP) activity found that in male adults testis they increased significantly than control during its development. Thus the present research investigation highlights that the 60Co-γ radiation treatments alters the physiological development of diamondback moth. The results showed that 200 Gy dosage resulted in stress damage to the body and reproductive system of the diamondback moth.


Assuntos
Antioxidantes/metabolismo , Radioisótopos de Cobalto/efeitos adversos , Proteínas de Choque Térmico HSP70/genética , Lepidópteros/efeitos da radiação , Soro/química , Fosfatase Ácida/metabolismo , Animais , Antioxidantes/efeitos da radiação , Raios gama/efeitos adversos , Regulação da Expressão Gênica/efeitos da radiação , Proteínas de Insetos/genética , L-Lactato Desidrogenase/metabolismo , Lepidópteros/enzimologia , Lepidópteros/metabolismo , Camundongos , Soro/efeitos da radiação
20.
Molecules ; 23(5)2018 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-29701672

RESUMO

Chemometric analysis of bioactive compounds revealed that American ginsengs (AGs) from different cultivation regions of China had a difference in quality, which indicates their possible pharmacological difference. A UPLC-Q/TOF-MS-based untargeted metabolomic approach was used to uncover serum metabolite changes in radiated mice pre-administered with AG root decoctions from seven cultivation regions and to further assess their quality difference. OPLS-DA revealed that 51 metabolites (ESI−) and 110 (ESI⁺) were differentially expressed in sera between the control and the radiated model mice. Heatmap analysis further revealed that AG could not reverse most of these radiation-altered metabolites, which indicates dietary supplement of AG before cobalt radiation had the weak potential to mediate serum metabolites that were altered by the sub-lethal high dose radiation. In addition, 83 (ESI−) and 244 (ESI⁺) AG altered metabolites were detected in radiated mice under radiation exposure. Both OPLS-DA on serum metabolomes and heatmap analysis on discriminant metabolites showed that AGs from different cultivation regions differentially influenced metabolic alterations in radiated mice, which indicates AGs from different cultivation regions showed the pharmacological difference in modulation of metabolite changes. AGs from Shandong, Shanxi, and Beijing provinces had more similar pharmacological effects than AGs from USA, Canada, Jilin, and Heilongjiang. Finally, 28 important potential biomarkers were annotated and assigned onto three metabolic pathways including lipid, amino acid, and energy metabolisms.


Assuntos
Radioisótopos de Cobalto/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Metabolômica/métodos , Panax/química , Soro/química , Animais , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Metaboloma/efeitos dos fármacos , Metaboloma/efeitos da radiação , Camundongos , Panax/classificação , Raízes de Plantas/química , Soro/efeitos dos fármacos , Soro/efeitos da radiação
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