RESUMEN

In this study, the protective effects of Panax notoginseng saponins (PNS) against gamma radiation-induced DNA damage and associated physiological alterations in Swiss albino mice were investigated. Exposure to gamma radiation led to a dose-dependent increase in cytokinesis-blocked micronuclei (CBMN) double-strand DNA breaks (DSBs), dicentric aberrations (DC), formation in peripheral blood mononuclear cells. However, pretreatment with PNS at concentrations of 1, 5, and 10 µg/mL significantly attenuated the frequencies of DC and CBMN in a concentration-dependent manner. PNS administration before radiation exposure also reduced radiation-induced DSBs in BL, indicating protection against reactive oxygen species generation and DNA damage. Notably, pretreatment with PNS at 10 µg/mL prevented the overexpression of γ-H2AX, proteins associated with DNA damage response, in irradiated mice. In addition, in vivo studies showed intraperitoneal administration of PNS (25 mg/kg body weight) for 1 h before radiation exposure mitigated lipid peroxidation levels and restored antioxidant status, countering oxidative damage induced by gamma radiation. Furthermore, PNS pretreatment reversed the decrease in hemoglobin (Hb) content, white blood cell count, and red blood cell count in irradiated mice, indicating preservation of hematological parameters. Overall, PNS demonstrated an anticlastogenic effect by modulating radiation-induced DSBs and preventing oxidative damage, thus highlighting its potential as a protective agent against radiation-induced DNA damage and associated physiological alterations. Clinically, PNS will be beneficial for cancer patients undergoing radiotherapy, but their pharmacological properties and toxicity profiles need to be studied.

Asunto(s)

Rayos gamma , Panax notoginseng , Saponinas , Animales , Rayos gamma/efectos adversos , Saponinas/farmacología , Ratones , Panax notoginseng/química , Humanos , Masculino , Daño del ADN/efectos de los fármacos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/efectos de la radiación , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Protectores contra Radiación/farmacología , Roturas del ADN de Doble Cadena/efectos de los fármacos , Roturas del ADN de Doble Cadena/efectos de la radiación , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Monocitos/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/farmacología

RESUMEN

Understanding the hazards of space radiation is imperative as astronauts begin voyaging on missions with increasing distances from Earth's protective shield. Previous studies investigating the acute or long-term effects of specific ions comprising space radiation have revealed threats to organs generally considered radioresistant, like the brain, and have shown males to be more vulnerable than their female counterparts. However, astronauts will be exposed to a combination of ions that may result in additive effects differing from those of any one particle species. To better understand this nuance, we irradiated 4-month-old male and female, wild-type and Alzheimer's-like mice with 0, 0.5, or 0.75 Gy galactic cosmic ray simulation (GCRsim) or 0, 0.75, or 2 Gy gamma radiation (wild-type only). At 11 months, mice underwent brain and heart MRIs or behavioral tests, after which they were euthanized to assess amyloid-beta pathology, heart and kidney gene expression and fibrosis, and plasma cytokines. Although there were no changes in amyloid-beta pathology, we observed many differences in brain MRIs and behavior, including opposite effects of GCRsim on motor coordination in male and female transgenic mice. Additionally, several genes demonstrated persistent changes in the heart and kidney. Overall, we found sex- and genotype-specific, long-term effects of GCRsim and gamma radiation on the brain, heart, and kidney.

Asunto(s)

Enfermedad de Alzheimer , Encéfalo , Radiación Cósmica , Rayos gamma , Corazón , Riñón , Ratones Transgénicos , Animales , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/etiología , Enfermedad de Alzheimer/patología , Femenino , Masculino , Rayos gamma/efectos adversos , Encéfalo/efectos de la radiación , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Ratones , Riñón/efectos de la radiación , Riñón/metabolismo , Riñón/patología , Corazón/efectos de la radiación , Radiación Cósmica/efectos adversos , Mutación , Caracteres Sexuales , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/genética , Modelos Animales de Enfermedad , Factores Sexuales

RESUMEN

The salivary glands are often damaged during head and neck cancer radiotherapy. This results in chronic dry mouth, which adversely affects quality of life and for which there is no long-term cure. Mouse models of salivary gland injury are routinely used in regenerative research. However, there is no clear consensus on the radiation regime required to cause injury. Here, we analysed three regimes of γ-irradiation of the submandibular salivary gland. Transcriptional analysis, immunofluorescence and flow cytometry was used to profile DNA damage, gland architecture and immune cell changes 3 days after single doses of 10 or 15 Gy or three doses of 5 Gy. Irrespective of the regime, radiation induced comparable levels of DNA damage, cell cycle arrest, loss of glandular architecture, increased pro-inflammatory cytokines and a reduction in tissue-resident macrophages, relative to those observed in non-irradiated submandibular glands. Given these data, coupled with the fact that repeated anaesthetic can negatively affect animal welfare and interfere with saliva secretion, we conclude that a single dose of 10 Gy irradiation is the most refined method of inducing acute salivary gland injury in a mouse model.

Asunto(s)

Daño del ADN , Fraccionamiento de la Dosis de Radiación , Ratones Endogámicos C57BL , Glándulas Salivales , Animales , Glándulas Salivales/efectos de la radiación , Glándulas Salivales/patología , Glándula Submandibular/efectos de la radiación , Glándula Submandibular/patología , Rayos gamma/efectos adversos , Citocinas/metabolismo , Ratones , Masculino , Macrófagos/efectos de la radiación , Macrófagos/patología , Macrófagos/metabolismo , Puntos de Control del Ciclo Celular/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Femenino

RESUMEN

A model for accelerated aging in mice was developed: CB6F2 mice aged 39-45 days were exposed to fractionated 4-fold relatively uniform γ-radiation (137Cs, 0.98 Gy/min) at a total dose of 6.8 Gy. Radiation exposure led to delayed active growth, leukopenia, and lymphopenia for over 1 year during the post-radiation period. The death of irradiated males and females occurred significantly earlier than in control group animals. Median lifespans in the experimental group were 35-38% lower than in the control group (p<0.001). Ionizing radiation exposure led to the early development of hair depigmentation, cachexia, and the development of aging-associated diseases. In irradiated mice, oncological pathology constituted 30-35% in the mortality structure, which is twice as often as in the control group. The developed model can be used to study the pathogenesis of accelerated aging under radiation exposure and the search for means of its prevention and treatment.

Asunto(s)

Envejecimiento Prematuro , Rayos gamma , Animales , Ratones , Masculino , Femenino , Rayos gamma/efectos adversos , Envejecimiento Prematuro/patología , Envejecimiento Prematuro/genética , Envejecimiento Prematuro/etiología , Longevidad/efectos de la radiación , Radiación Ionizante , Envejecimiento/efectos de la radiación , Caquexia/patología , Caquexia/etiología , Radioisótopos de Cesio

RESUMEN

Animal studies are needed that best simulate a large-scale, inhomogeneous body exposure after a radiological or nuclear incident and that provides a platform for future development of medical countermeasures. A partial-body irradiation (PBI) model using 137Cs gamma rays with hind limb (tibia) shielding was developed and assessed for the sequalae of radiation injuries to gastrointestinal tract, bone marrow (BM) and lung and among different genetic mouse strains (C57BL/6J, C57L/J, CBA/J and FVB/NJ). In this case, a marginal level of BM shielding (∼2%) provided adequate protection against lethality from infection and hemorrhage and enabled escalation of radiation doses with evaluation of both acute and delayed radiation syndromes. A steep radiation dose-dependent body weight loss was observed over the first 5 days attributed to enteritis with C57BL/6J mice appearing to be the most sensitive strain. Peripheral blood cell analysis revealed significant depression and recovery of leukocytes and platelets over the first month after PBI and were comparable among the four different mouse strains. Latent pulmonary injury was observed on micro-CT imaging at 4 months in C57L/J mice and confirmed histologically as severe pneumonitis that was lethal at 12 Gy. The lethality and radiological densitometry (HUs) dose responses were comparable to previous studies on C57L/J mice after total-body irradiation (TBI) and BM transplant rescue as well as after localized whole-thorax irradiation (WTI). Indeed, the lethal radiation doses and latency appeared similar for pneumonitis appearing in rhesus macaques after WTI or PBI as well as predicted for patients given systemic radiotherapy. In contrast, PBI treatment of C57BL/6 mice at a higher dose of 14 Gy had far longer survival times and developed extreme and debilitating pIeural effusions; an anomaly as similarly reported in previous thorax irradiation studies on this mouse strain. In summary, a radiation exposure model that delivers PBI to unanesthetized mice in a device that provides consistent shielding of the hind limb BM was developed for 137Cs gamma rays with physical characteristics and relevance to relatively high photon energies expected from the detonation of a nuclear device or accidental release of ionizing radiation. Standard strains such as C57BL/6J mice may be used reliably for early GI or hematological radiation syndromes while the C57L/J mouse strain stands out as the most appropriate for evaluating the delayed pulmonary effects of acute radiation exposure and recapitulating this disease in humans.

Asunto(s)

Rayos gamma , Animales , Ratones , Rayos gamma/efectos adversos , Traumatismos Experimentales por Radiación/patología , Traumatismos Experimentales por Radiación/etiología , Traumatismos Experimentales por Radiación/diagnóstico por imagen , Relación Dosis-Respuesta en la Radiación , Masculino , Ratones Endogámicos C57BL , Femenino , Especificidad de la Especie , Radioisótopos de Cesio , Médula Ósea/efectos de la radiación , Médula Ósea/patología

RESUMEN

Throughout radiotherapy, radiation of the hepatic tissue leads to damage of the hepatocytes. We designed the current study to examine how cerium oxide nanoparticles (CONPs) modulate gamma irradiation-induced hepatotoxicity in rats. Animals received CONPs (15 mg/kg body weight [BW], ip) single daily dose for 14 days, and they were exposed on the seventh day to a single dose of gamma radiation (6 Gy). Results showed that irradiation increased serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activities. Furthermore, it elevated oxidative stress biomarker; malondialdehyde (MDA) and inhibited the activities of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in hepatic tissues homogenate. Additionally, hepatic apoptotic markers; caspase-3 (Casp-3) and Casp-9 were elevated and the B-cell lymphoma-2 (Bcl-2) gene level was decreased in rats exposed to radiation dose. We observed that CONPs can modulate these changes, where CONPs reduced liver enzyme activities, MDA, and apoptotic markers levels, in addition, it elevated antioxidant enzyme activities and Bcl-2 gene levels, as well as improved histopathological changes in the irradiated animals. So our results concluded that CONPs had the ability to act as radioprotector defense against hepatotoxicity resulted during radiotherapy.

Asunto(s)

Antioxidantes , Apoptosis , Cerio , Rayos gamma , Hígado , Nanopartículas , Cerio/farmacología , Cerio/química , Animales , Rayos gamma/efectos adversos , Apoptosis/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/metabolismo , Ratas , Masculino , Hígado/efectos de los fármacos , Hígado/efectos de la radiación , Hígado/metabolismo , Hígado/patología , Nanopartículas/química , Ratas Wistar , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Alanina Transaminasa/metabolismo , Alanina Transaminasa/sangre , Malondialdehído/metabolismo , Aspartato Aminotransferasas/metabolismo , Aspartato Aminotransferasas/sangre , Superóxido Dismutasa/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo

RESUMEN

BACKGROUND AND AIM: The spleen has an essential role in immune responses regulation and is considered the biggest peripheral immune organ. Citicoline is used for various brain disorders management. This study aimed to examine the using possibility of citicoline to treat γ-radiation-induced splenic inflammation in rats. MATERIALS AND METHODS: Eighteen male albino rats were classified into: Group 1 (control) animals were kept as control. Group 2 (γ-radiation) animals were total-body γ-irradiated with 6 Gy. Group 3 (γ-radiation + citicoline) rats were γ-irradiated with 6 Gy, then injected intraperitoneally with citicoline (300 mg/kg/d) 5 min after irradiation for one week. Levels of TNF-α, IL-1ß, iNOS, NF-κB, JAK2, and STAT3 were determined in spleen tissue, along with histopathological examination. RESULTS: Rats exposure to gamma-radiation led to elevation in splenic TNF-α, IL-1ß, NF-κB, iNOS, JAK2, and STAT3 levels significantly. Treatment with citicoline after gamma-radiation exposure improved this elevation, and modulated gamma-radiation-induced histopathological alterations. CONCLUSIONS: This data showed that citicoline inhibited γ-radiation-induced splenic inflammation via suppressing NF-κB and JAK2/STAT3 signaling pathways in spleen tissue.

Asunto(s)

Citidina Difosfato Colina , Rayos gamma , Transducción de Señal , Bazo , Animales , Rayos gamma/efectos adversos , Masculino , Bazo/efectos de los fármacos , Bazo/efectos de la radiación , Bazo/patología , Bazo/inmunología , Ratas , Transducción de Señal/efectos de los fármacos , Transducción de Señal/efectos de la radiación , Citidina Difosfato Colina/farmacología , Inflamación/tratamiento farmacológico , FN-kappa B/metabolismo , Irradiación Corporal Total

RESUMEN

BACKGROUND: Adaptation to a stressor can lead to costs on other traits. These costs play an unavoidable role on fitness and influence the evolutionary trajectory of a population. Host defense seems highly subject to these costs, possibly because its maintenance is energetically costly but essential to the survival. When assessing the ecological risk related to pollution, it is therefore relevant to consider these costs to evaluate the evolutionary consequences of stressors on populations. However, to the best of our knowledge, the effects of evolution in irradiate environment on host defense have never been studied. Using an experimental evolution approach, we analyzed fitness across 20 transfers (about 20 generations) in Caenorhabditis elegans populations exposed to 0, 1.4, and 50.0 mGy.h- 1 of 137Cs gamma radiation. Then, populations from transfer 17 were placed in the same environmental conditions without irradiation (i.e., common garden) for about 10 generations before being exposed to the bacterial parasite Serratia marcescens and their survival was estimated to study host defense. Finally, we studied the presence of an evolutionary trade-off between fitness of irradiated populations and host defense. RESULTS: We found a lower fitness in both irradiated treatments compared to the control ones, but fitness increased over time in the 50.0 mGy.h- 1, suggesting a local adaptation of the populations. Then, the survival rate of C. elegans to S. marcescens was lower for common garden populations that had previously evolved under both irradiation treatments, indicating that evolution in gamma-irradiated environment had a cost on host defense of C. elegans. Furthermore, we showed a trade-off between standardized fitness at the end of the multigenerational experiment and survival of C. elegans to S. marcescens in the control treatment, but a positive correlation between the two traits for the two irradiated treatments. These results indicate that among irradiated populations, those most sensitive to ionizing radiation are also the most susceptible to the pathogen. On the other hand, other irradiated populations appear to have evolved cross-resistance to both stress factors. CONCLUSIONS: Our study shows that adaptation to an environmental stressor can be associated with an evolutionary cost when a new stressor appears, even several generations after the end of the first stressor. Among irradiated populations, we observed an evolution of resistance to ionizing radiation, which also appeared to provide an advantage against the pathogen. On the other hand, some of the irradiated populations seemed to accumulate sensitivities to stressors. This work provides a new argument to show the importance of considering evolutionary changes in ecotoxicology and for ecological risk assessment.

Asunto(s)

Evolución Biológica , Caenorhabditis elegans , Animales , Caenorhabditis elegans/efectos de la radiación , Caenorhabditis elegans/microbiología , Radiación Ionizante , Serratia marcescens , Rayos gamma/efectos adversos , Aptitud Genética

RESUMEN

The increased risk of liver malignancies was found in workers of the first Russian nuclear production facility, Mayak Production Association, who had been chronically exposed to gamma rays externally and to alpha particles internally due to plutonium inhalation. In the present study, we updated the radiogenic risk estimates of the hepatobiliary malignancies using the extended follow-up period (1948-2018) of the Mayak worker cohort and the improved «Mayak worker dosimetry system-2013¼. The cohort comprised 22,377 workers hired at the Mayak PA between 1948 and 1982. The analysis considered 62 liver malignancies (32 hepatocellular carcinomas, 13 intrahepatic cholangiocarcinomas, 16 angiosarcomas, and 1 anaplastic cancer) and 33 gallbladder adenocarcinomas. The analysis proved the positive significant association of the liver malignancy risk (the total of histological types, hepatocellular carcinoma) with the liver absorbed alpha dose from internal exposure. The excess relative risk per Gy (95% confidence interval) of alpha dose (the linear model) was 7.56 (3.44; 17.63) for the total of histological types and 3.85 (0.95; 13.30) for hepatocellular carcinoma. Indications of non-linearity were observed in the dose-response for internal exposure to alpha radiation. No impact of external gamma-ray exposure on the liver malignancy incidence was found. In the study cohort, the number of angiosarcomas among various types of liver malignancies was very high (25.8%), and most of these tumors (73.3%) were registered in individuals internally exposed to alpha radiation at doses ranging between 6.0 and 21.0 Gy. No association with chronic occupational radiation exposure was observed for the incidence of gallbladder malignancies.

Asunto(s)

Neoplasias Hepáticas , Neoplasias Inducidas por Radiación , Exposición Profesional , Humanos , Exposición Profesional/efectos adversos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Masculino , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Inducidas por Radiación/etiología , Incidencia , Persona de Mediana Edad , Femenino , Radiación Ionizante , Estudios de Cohortes , Adulto , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Federación de Rusia/epidemiología , Anciano , Partículas alfa/efectos adversos , Rayos gamma/efectos adversos , Exposición a la Radiación/efectos adversos

RESUMEN

Research on plant and animal peptides has garnered significant attention, but there is a lack of studies on the functional properties of Tenebrio molitor peptides, particularly in relation to their potential mitigating effect on radiation damage and the underlying mechanisms. This study aims to explore the protective effects of Tenebrio molitor peptides against radiation-induced damage. Mice were divided into five groups: normal, radiation model, and low-, medium-, and high-dose Tenebrio molitor peptide (TMP) groups (0.15 g per kg BW, 0.30 g per kg BW, and 0.60 g per kg BW). Various parameters such as blood cell counts, bone marrow DNA content, immune organ indices, serum levels of D-lactic acid, diamine oxidase (DAO), endotoxin (LPS), and inflammatory factors were assessed at 3 and 15 days post gamma irradiation. Additionally, the intestinal tissue morphology was examined through H&E staining, RT-qPCR experiments were conducted to analyze the expression of inflammatory factors in the intestine, and immunohistochemistry was utilized to evaluate the expression of tight junction proteins ZO-1 and Occludin in the intestine. The findings revealed that high-dose TMP significantly enhanced the hematopoietic system function in mice post radiation exposure, leading to increased spleen index, thymus index, blood cell counts, and bone marrow DNA production (p < 0.05). Moreover, TMP improved the intestinal barrier integrity and reduced the intestinal permeability. Mechanistic insights suggested that these peptides may safeguard intestinal barrier function by downregulating the gene expression of inflammatory factors TNF-α, IL-1ß, and IL-6, while upregulating the expression of tight junction proteins ZO-1 and Occludin (p < 0.05). Overall, supplementation with TMP mitigates radiation-induced intestinal damage by enhancing the hematopoietic system and the intestinal barrier, offering valuable insights for further investigations into the mechanisms underlying the protective effects of these peptides against ionizing radiation.

Asunto(s)

Mucosa Intestinal , Péptidos , Tenebrio , Animales , Ratones , Péptidos/farmacología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de la radiación , Mucosa Intestinal/efectos de los fármacos , Masculino , Sistema Hematopoyético/efectos de los fármacos , Sistema Hematopoyético/efectos de la radiación , Protectores contra Radiación/farmacología , Proteína de la Zonula Occludens-1/metabolismo , Proteína de la Zonula Occludens-1/genética , Rayos gamma/efectos adversos , Ocludina/metabolismo , Ocludina/genética , Intestinos/efectos de los fármacos , Intestinos/efectos de la radiación

RESUMEN

High doses of ionizing radiation are the risk factor of cognitive dysfunction and anxiety disorders developing in humans and experimental animals. However, the data on the effect of low doses, especially in case of chronic or fractionated exposure, is limited and contradictory. Here we studied the effect of fractionated γ-radiation at cumulative doses of 0.1, 1, and 5 Gy on the parameters of the anxiety-like behavior in neonatal C57BL/6 mice. The anxiety was evaluated using the marble burying test and elevated plus maze. Fractionated irradiation resulted in dose-dependent changes in mouse behavior: the low dose caused an increase in anxiety, wherein the dose raise led to the decrease in anxiety-like behavior indicators compared to non-irradiated animals.

Asunto(s)

Animales Recién Nacidos , Ansiedad , Conducta Animal , Relación Dosis-Respuesta en la Radiación , Rayos gamma , Ratones Endogámicos C57BL , Animales , Rayos gamma/efectos adversos , Ratones , Conducta Animal/efectos de la radiación , Masculino , Aprendizaje por Laberinto/efectos de la radiación , Fraccionamiento de la Dosis de Radiación , Femenino

RESUMEN

In orbital and ground-based experiments, it has been demonstrated that ionizing radiation (IR) can stimulate the locomotor and exploratory activity of rodents, but the underlying mechanism of this phenomenon remains undisclosed. Here, we studied the effect of combined IR (0.4 Gy γ-rays and 0.14 Gy carbon-12 nuclei) on the locomotor and exploratory activity of rats, and assessed the sensorimotor cortex volume by magnetic resonance imaging-based morphometry at 1 week and 7 months post-irradiation. The sensorimotor cortex tissues were processed to determine whether the behavioral and morphologic effects were associated with changes in neurotrophin content. The irradiated rats were characterized by increased locomotor and exploratory activity, as well as novelty-seeking behavior, at 3 days post-irradiation. At the same time, only unirradiated rats experienced a significant decrease in the sensorimotor cortex volume at 7 months. While there were no significant differences at 1 week, at 7 months, the irradiated rats were characterized by higher neurotrophin-3 and neurotrophin-4 content in the sensorimotor cortex. Thus, IR prevents the age-associated decrease in the sensorimotor cortex volume, which is associated with neurotrophic and neurogenic changes. Meanwhile, IR-induced increases in locomotor activity may be the cause of the observed changes.

Asunto(s)

Rayos gamma , Factores de Crecimiento Nervioso , Corteza Sensoriomotora , Animales , Corteza Sensoriomotora/metabolismo , Corteza Sensoriomotora/efectos de la radiación , Rayos gamma/efectos adversos , Ratas , Masculino , Factores de Crecimiento Nervioso/metabolismo , Radiación Ionizante , Neurotrofina 3/metabolismo , Envejecimiento , Locomoción/efectos de la radiación , Imagen por Resonancia Magnética

RESUMEN

Background: Owing to the long penetration depth of gamma (γ)-rays, individuals working in ionizing radiation environments are chronically exposed to low-dose γ-radiation, resulting in cognitive changes. Dose rate significantly affects radiation-induced biological effects; however, its role in chronic low-dose γ-irradiation-induced cognitive impairment remains unclear. We aimed to investigate whether chronic low-dose γ-irradiation at low-dose-rate (LDR) could induce cognitive impairment and to compare the cognitive alteration caused by chronic low-dose γ-irradiation at LDR and high-dose-rate (HDR). Methods: The rats were exposed to γ-irradiation at a LDR of 6 mGy/h and a HDR of 20 mGy/h for 30 days (5 h/day). Functional imaging was performed to assess the brain inflammation and blood-brain barrier (BBB) destruction of rats. Histological and immunofluorescence analyses were used to reveal the neuron damage and the activation of microglia and astrocytes in the hippocampus. RNA sequencing was conducted to investigate changes in gene expression in hippocampus. Results: The rats in the LDR group exhibited more persistent cognitive impairment than those in the HDR group. Furthermore, irradiated rats showed brain inflammation and a compromised BBB. Histologically, the number of hippocampal neurons were comparable in the LDR group but were markedly decreased in the HDR. Additionally, activated M1-like microglia and A1-like astrocytes were observed in the hippocampus of rats in the LDR group; however, only M1-like microglia were activated in the HDR group. Mechanistically, the PI3K-Akt signaling pathway contributed to the different cognitive function change between the LDR group and HDR group. Conclusion: Compared with chronic low-dose γ-irradiation at HDR, LDR induced more severe cognitive impairment which might involve PI3K/Akt signaling pathway.

Asunto(s)

Disfunción Cognitiva , Rayos gamma , Animales , Rayos gamma/efectos adversos , Ratas , Disfunción Cognitiva/etiología , Masculino , Hipocampo/efectos de la radiación , Ratas Sprague-Dawley , Relación Dosis-Respuesta en la Radiación , Barrera Hematoencefálica/efectos de la radiación

RESUMEN

<b>Background and Objective:</b> Gamma irradiation induces genotoxicity, characterized by the formation of extra-nuclear bodies and left behind during the anaphase stage of cell division, often referred to as a micronucleus (MN). The present work aims to monitor exposure to ionizing radiation as a genotoxic agent in the lymphocytes of workers at radiation energy centers. <b>Materials and Methods:</b> The lymphocyte cytokinesis block micronucleus assay used and analyzed the correlation between the Nuclear Division Index (NDI), age, blood type and the number of micronuclei (MN). Blood samples were collected from 20 volunteers in heparin tubes, exposed to 2 Gy gamma rays and cultured <i>in vitro</i>. <b>Results:</b> A significant difference in the number of micronuclei between blood group A and blood groups A, B and AB. The Nuclear Division Index (NDI) value for lymphocytes of radiation energy center workers after gamma radiation was significant (1.74±0.1) but still within the normal range. Neither MN frequency nor NDI values correlated with age, but MN frequency showed a correlation with blood type. <b>Conclusion:</b> The gamma irradiation did not induce a cytostatic effect but proved genotoxic to the lymphocytes of radiation energy center workers. Notably, blood type A demonstrated higher sensitivity to gamma radiation.

Asunto(s)

Citocinesis , Rayos gamma , Linfocitos , Pruebas de Micronúcleos , Exposición Profesional , Humanos , Rayos gamma/efectos adversos , Linfocitos/efectos de la radiación , Linfocitos/metabolismo , Pruebas de Micronúcleos/métodos , Citocinesis/efectos de la radiación , Exposición Profesional/efectos adversos , Adulto , Masculino , Persona de Mediana Edad , Micronúcleos con Defecto Cromosómico/efectos de la radiación , Femenino

RESUMEN

Ionizing radiation produces deleterious effects on living organisms. The present investigation has been carried out to study the prophylactic as well as the therapeutic effects of treated rats with quercetin (Quer) and curcumin (Cur), which are two medicinal herbs known for their antioxidant activities against damages induced by whole-body fractionated gamma irradiation. Exposure of rats to whole-body gamma irradiation induced a significant decrease in erythrocyte (RBC), leukocyte (WBCs), platelet count (Plt), hemoglobin concentration (Hb), hematocrit (Hct %), mean erythrocyte hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and mean erythrocyte volume (MCV); a high increase in plasma thiobarbituric acid reactive substances (TBARS); a nonsignificant statistical decrease in the mean value of serum glutathione (GSH); a significant increase in plasma alanine transferase (ALT), aspartate transferase (AST), alkaline phosphates (ALP), serum total protein, serum total cholesterol levels, total triglycerides levels, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels; and with marked histological changes and structural changes measured by Fourier transform infrared (FTIR). Applying both quercetin and curcumin pre- and postexposure to gamma radiation revealed a remarkable improvement in all the studied parameters. The cellular damage by gamma radiation is greatly mitigated by the coadministration of curcumin and quercetin before radiation exposure.

Asunto(s)

Curcumina , Rayos gamma , Hígado , Quercetina , Animales , Quercetina/farmacología , Curcumina/farmacología , Rayos gamma/efectos adversos , Ratas , Masculino , Hígado/efectos de los fármacos , Hígado/efectos de la radiación , Hígado/metabolismo , Hígado/patología , Antioxidantes/farmacología , Ratas Wistar

RESUMEN

The identification and validation of radiation biomarkers is critical for assessing the radiation dose received in exposed individuals and for developing radiation medical countermeasures that can be used to treat acute radiation syndrome (ARS). Additionally, a fundamental understanding of the effects of radiation injury could further aid in the identification and development of therapeutic targets for mitigating radiation damage. In this study, blood samples were collected from fourteen male nonhuman primates (NHPs) that were exposed to 7.2 Gy ionizing radiation at various time points (seven days prior to irradiation; 1, 13, and 25 days post-irradiation; and immediately prior to the euthanasia of moribund (preterminal) animals). Plasma was isolated from these samples and was analyzed using a liquid chromatography tandem mass spectrometry approach in an effort to determine the effects of radiation on plasma proteomic profiles. The primary objective was to determine if the radiation-induced expression of specific proteins could serve as an early predictor for health decline leading to a preterminal phenotype. Our results suggest that radiation induced a complex temporal response in which some features exhibit upregulation while others trend downward. These statistically significantly altered features varied from pre-irradiation levels by as much as tenfold. Specifically, we found the expression of integrin alpha and thrombospondin correlated in peripheral blood with the preterminal stage. The differential expression of these proteins implicates dysregulation of biological processes such as hemostasis, inflammation, and immune response that could be leveraged for mitigating radiation-induced adverse effects.

Asunto(s)

Rayos gamma , Macaca mulatta , Proteómica , Animales , Rayos gamma/efectos adversos , Masculino , Proteómica/métodos , Biomarcadores/sangre , Irradiación Corporal Total/efectos adversos , Síndrome de Radiación Aguda/sangre , Síndrome de Radiación Aguda/etiología , Proteínas Sanguíneas/análisis , Proteínas Sanguíneas/metabolismo , Proteoma/análisis , Proteoma/metabolismo

RESUMEN

Using the method of dominant lethal mutations, we assessed the frequency of the death of Drosophila melanogaster embryos under combined exposure to ionizing γ-radiation and non-ionizing pulsed magnetic field at various doses and modes of exposure. Mutagenic effect of combined exposure is antagonistic in nature. The antagonism is more pronounced when the following mode of exposure was used: exposure to non-ionizing pulsed magnetic field for 5 h followed by exposure to γ-radiation at doses of 3, 10, and 60 Gy. In case of reverse sequence of exposures, the antagonistic effect was statistically significant after exposure to γ-radiation at doses of 3 and 10 Gy, whereas at a dose of 20 Gy, a synergistic interaction was noted.

Asunto(s)

Drosophila melanogaster , Rayos gamma , Animales , Drosophila melanogaster/efectos de la radiación , Drosophila melanogaster/genética , Rayos gamma/efectos adversos , Radiación Electromagnética , Relación Dosis-Respuesta en la Radiación , Campos Electromagnéticos/efectos adversos , Embrión no Mamífero/efectos de la radiación , Radiación Ionizante , Mutación/efectos de la radiación , Mutagénesis/efectos de la radiación

RESUMEN

The knowledge on responses of human lens epithelial cells (HLECs) to ionizing radiation exposure is important to understand mechanisms of radiation cataracts that are of concern in the field of radiation protection and radiation therapy. However, biological effects in HLECs following protracted exposure have not yet fully been explored. Here, we investigated the temporal kinetics of γ-H2AX foci as a marker for DNA double-strand breaks (DSBs) and cell survival in HLECs after exposure to photon beams at various dose rates (i.e., 150 kVp X-rays at 1.82, 0.1, and 0.033 Gy/min, and 137Cs γ-rays at 0.00461 Gy/min (27.7 cGy/h) and 0.00081 Gy/min (4.9 cGy/h)), compared to those in human lung fibroblasts (WI-38). In parallel, we quantified the recovery for DSBs and cell survival using a biophysical model. The study revealed that HLECs have a lower DSB repair rate than WI-38 cells. There is no significant impact of dose rate on cell survival in both cell lines in the dose-rate range of 0.033-1.82 Gy/min. In contrast, the experimental residual γ-H2AX foci showed inverse dose rate effects (IDREs) compared to the model prediction, highlighting the importance of the IDREs in evaluating radiation effects on the ocular lens.

Asunto(s)

Supervivencia Celular , Roturas del ADN de Doble Cadena , Relación Dosis-Respuesta en la Radiación , Células Epiteliales , Histonas , Cristalino , Humanos , Células Epiteliales/efectos de la radiación , Células Epiteliales/metabolismo , Cristalino/efectos de la radiación , Cristalino/citología , Roturas del ADN de Doble Cadena/efectos de la radiación , Histonas/metabolismo , Supervivencia Celular/efectos de la radiación , Radiación Ionizante , Línea Celular , Reparación del ADN/efectos de la radiación , Fibroblastos/efectos de la radiación , Fibroblastos/metabolismo , Rayos X , Rayos gamma/efectos adversos

RESUMEN

The biological mechanisms triggered by low-dose exposure still need to be explored in depth. In this study, the potential mechanisms of low-dose radiation when irradiating the BEAS-2B cell lines with a Cs-137 gamma-ray source were investigated through simulations and experiments. Monolayer cell population models were constructed for simulating and analyzing distributions of nucleus-specific energy within cell populations combined with the Monte Carlo method and microdosimetric analysis. Furthermore, the 10 × Genomics single-cell sequencing technology was employed to capture the heterogeneity of individual cell responses to low-dose radiation in the same irradiated sample. The numerical uncertainties can be found both in the specific energy distribution in microdosimetry and in differential gene expressions in radiation cytogenetics. Subsequently, the distribution of nucleus-specific energy was compared with the distribution of differential gene expressions to guide the selection of differential genes bioinformatics analysis. Dose inhomogeneity is pronounced at low doses, where an increase in dose corresponds to a decrease in the dispersion of cellular-specific energy distribution. Multiple screening of differential genes by microdosimetric features and statistical analysis indicate a number of potential pathways induced by low-dose exposure. It also provides a novel perspective on the selection of sensitive biomarkers that respond to low-dose radiation.

Asunto(s)

Relación Dosis-Respuesta en la Radiación , Análisis de la Célula Individual , Análisis de la Célula Individual/métodos , Humanos , Método de Montecarlo , Radiometría/métodos , Línea Celular , Rayos gamma/efectos adversos

RESUMEN

Although there are several types of radiation exposure, it is debated whether low­dose­rate (LDR) irradiation (IR) affects the body. Since the small intestine is a radiation­sensitive organ, the present study aimed to evaluate how it changes when exposed to LDR IR and identify the genes sensitive to these doses. After undergoing LDR (6.0 mGy/h) γ radiation exposure, intestinal RNA from BALB/c mice was extracted 1 and 24 h later. Mouse whole genome microarrays were used to explore radiation­induced transcriptional alterations. Reverse transcription­quantitative (RT­q) PCR was used to examine time­ and dose­dependent radiation responses. The histopathological status of the jejunum in the radiated mouse was not changed by 10 mGy of LDR IR; however, 23 genes were upregulated in response to LDR IR of the jejunum in mice after 1 and 24 h of exposure. Upregulated genes were selected to validate the results of the RNA sequencing analysis for RT­qPCR detection and results showed that only Na+/K+ transporting subunit α4, glucose­6­phosphatase catalytic subunit 2 (G6PC2), mucin 6 (MUC6) and transient receptor potential cation channel subfamily V member 6 levels significantly increased after 24 h of LDR IR. Furthermore, G6PC2 and MUC6 were notable genes induced by LDR IR exposure according to protein expression via western blot analysis. The mRNA levels of G6PC2 and MUC6 were significantly elevated within 24 h under three conditions: i) Exposure to LDR IR, ii) repeated exposure to LDR IR and iii) exposure to LDR IR in the presence of inflammatory bowel disease. These results could contribute to an improved understanding of immediate radiation reactions and biomarker development to identify radiation­susceptible individuals before histopathological changes become noticeable. However, further investigation into the specific mechanisms involving G6PC2 and MUC6 is required to accomplish this.

Asunto(s)

Glucosa-6-Fosfatasa , Enfermedades Inflamatorias del Intestino , Mucina 6 , Animales , Masculino , Ratones , Relación Dosis-Respuesta en la Radiación , Rayos gamma/efectos adversos , Glucosa-6-Fosfatasa/metabolismo , Glucosa-6-Fosfatasa/genética , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/patología , Enfermedades Inflamatorias del Intestino/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de la radiación , Mucosa Intestinal/patología , Intestinos/efectos de la radiación , Intestinos/patología , Yeyuno/efectos de la radiación , Yeyuno/metabolismo , Yeyuno/patología , Ratones Endogámicos BALB C , Mucina 6/metabolismo , Mucina 6/genética