RESUMO
Exposure to ionizing radiation can result in the development of a number of diseases, including cancer, cataracts and neurodegenerative pathologies. Certain occupational groups are exposed to both natural and artificial sources of radiation as a consequence of their professional activities. The development of non-invasive biomarkers to assess the risk of exposure to ionizing radiation for these groups is of great importance. In this context, our objective was to identify epigenetic and molecular biomarkers that could be used to monitor exposure to ionizing radiation. The impact of X-ray exposure on the miRNAs profile and the level of cf mtDNA were evaluated using the RT-PCR method. The levels of pro-inflammatory cytokines in their blood were quantified using the ELISA method. A significant decrease in miR-19a-3p, miR-125b-5p and significant increase in miR-29a-3p was observed in the blood plasma of individuals exposed to X-ray. High levels of pro-inflammatory cytokines and cf mtDNA were also detected. In silico identification of potential targets of these miRNAs was conducted using MIENTURNET. VDAC1 and ALOX5 were identified as possible targets. Our study identified promising biomarkers such as miRNAs and cf mtDNA that showed a dose-dependent effect of X-ray exposure.
Assuntos
Biomarcadores , DNA Mitocondrial , Epigênese Genética , MicroRNAs , Humanos , MicroRNAs/sangue , MicroRNAs/genética , DNA Mitocondrial/sangue , DNA Mitocondrial/genética , Epigênese Genética/efeitos da radiação , Biomarcadores/sangue , Raios X/efeitos adversos , Masculino , Exposição Ocupacional/efeitos adversos , Adulto , Pessoa de Meia-Idade , Citocinas/sangue , Citocinas/genética , FemininoRESUMO
The use of vitamin C (VC) in high doses demonstrates a potent tumor suppressive effect by mediating a glucose-dependent oxidative stress in Kirsten rat sarcoma (KRAS) mutant cancer cells. VC with arsenic trioxide (ATO) is a promising drug combination that might lead to the development of effective cancer therapeutics. Considering that a tumor suppressive effect of VC requires its high-dose administration, it is of interest to examine the toxicity of two enantiomers of VC (enantiomer d-optical isomer D-VC and natural l-optical isomer L-VC) in vitro and in vivo. We show that the combinations of L-VC with ATO and D-VC with ATO induced a similar cytotoxic oxidative stress in KrasG12D-expressing mutant cancer cells as indicated by a substantial increase in reactive oxidative species (ROS) production and depolarization of mitochondria. To examine the L-VC and D-VC toxicity effects, we administered high doses of D-VC and L-VC to CD1 mice and carried out an evaluation of their toxic effects. The daily injections of L-VC at a dose of 9.2 g/kg for 18 days were lethal to mice, while 80% of mice remained alive following the similar high-dose administration of D-VC. Following the drug injection courses and histopathological studies, we determined that a natural form of VC (L-VC) is more harmful and toxic to mice when compared to the effects caused by the similar doses of D-VC. Thus, our study indicates that the two enantiomers of VC have a similar potency in the induction of oxidative stress in cancer cells, but D-VC has a distinctive lower toxicity in mice compared to L-VC. While the mechanism of a distinctive toxicity between D-VC and L-VC is yet to be defined, our finding marks D-VC as a more preferable option compared to its natural enantiomer L-VC in clinical settings.
Assuntos
Ácido Ascórbico , Neoplasias , Animais , Camundongos , Ácido Ascórbico/farmacologia , Proteínas Proto-Oncogênicas p21(ras) , Estresse Oxidativo , Vitaminas/farmacologia , Trióxido de Arsênio/farmacologiaRESUMO
: The main purpose of this work is to study the effectiveness of using FeCeOx nanocomposites doped with Nb2O5 for the purification of aqueous solutions from manganese. X-ray diffraction, energy-dispersive analysis, scanning electron microscopy, vibrational magnetic spectroscopy, and mössbauer spectroscopy were used as research methods. It is shown that an increase in the dopant concentration leads to the transformation of the shape of nanoparticles from spherical to cubic and rhombic, followed by an increase in the size of the nanoparticles. The spherical shape of the nanoparticles is characteristic of a structure consisting of a mixture of two phases of hematite (Fe2O3) and cerium oxide CeO2. The cubic shape of nanoparticles is typical for spinel-type FeNbO4 structures, the phase contribution of which increases with increasing dopant concentration. It is shown that doping leads not only to a decrease in the concentration of manganese in model solutions, but also to an increase in the efficiency of adsorption from 11% to 75%.
RESUMO
This review discusses the relationship between cellular senescence and radiation exposure. Given the wide range of ionizing radiation sources encountered by people in professional and medical spheres, as well as the influence of natural background radiation, the question of the effect of radiation on biological processes, particularly on aging processes, remains highly relevant. The parallel relationship between natural and radiation-induced cellular senescence reveals the common aspects underlying these processes. Based on recent scientific data, the key points of the effects of ionizing radiation on cellular processes associated with aging, such as genome instability, mitochondrial dysfunction, altered expression of miRNAs, epigenetic profile, and manifestation of the senescence-associated secretory phenotype (SASP), are discussed. Unraveling the molecular mechanisms of cellular senescence can make a valuable contribution to the understanding of the molecular genetic basis of age-associated diseases in the context of environmental exposure.
Assuntos
Envelhecimento , Senescência Celular , Humanos , Senescência Celular/genética , Células Cultivadas , Radiação IonizanteRESUMO
Asbestos is a known carcinogen; however, the influence of chrysotile asbestos on the development of tumor-related diseases remains a subject of intense debate within the scientific community. To analyze the effect of asbestos, we conducted a study using the MRC5 cell line. We were able to demonstrate that chrysotile asbestos stimulated the production of reactive oxygen species (ROS), leading to cell death and DNA damage in the MRC5 cell line, using various techniques such as ROS measurement, comet assay, MTT assay, and qPCR. In addition, we found that chrysotile asbestos treatment significantly increased extracellular mitochondrial DNA levels in the culture medium and induced significant changes in the expression profile of several miRNAs, which was the first of its kind. Thus, our research highlights the importance of studying the effects of chrysotile asbestos on human health and reveals multiple adverse effects of chrysotile asbestos.