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1.
Dokl Biochem Biophys ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39023669

RESUMEN

Radiosensitivity to low and medium doses of X-ray radiation and the ability to induce a radiation adaptive response (RAR) of lymphocytes during in vitro irradiation of peripheral blood of patients with cancer were studied. The criterion for cytogenetic damage was the frequency of micronuclei (MN) in cytochalasin-blocked binucleate lymphocytes in culture. It was found that the spontaneous level of cytogenetic damage in the lymphocytes of patients was 2.6 times higher than in healthy volunteers, and there was also significant interindividual variability in values compared to the control cohort. There were no differences in mean values for radiosensitivity to low and medium doses of X-ray between the study groups. There was no correlation between the spontaneous level of MN in lymphocytes and the radiosensitivity of individuals in both groups. RAR was induced with the same frequency and to the same extent in lymphocytes from both patients and healthy individuals.

2.
Chemosphere ; 363: 142888, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39032731

RESUMEN

Glyphosate is the most widely used systemic herbicide. There is ample scientific literature on the effects of this compound and its metabolite aminomethylphosphonic acid (AMPA), whereas their possible combined genotoxic action has not yet been studied. With the present study, we aimed to determine the level of genomic damage caused by glyphosate and AMPA in cultured human lymphocytes and to investigate the possible genotoxic action when both compounds were present at the same concentrations in the cultures. We used a micronuclei assay to test the genotoxicity of glyphosate and AMPA at six concentrations (0.0125, 0.025, 0.050, 0.100, 0.250, 0.500 µg/mL), which are more realistic than the highest concentrations used in previous published studies. Our data showed an increase in micronuclei frequency after treatment with both glyphosate and AMPA starting from 0.050 µg/mL up to 0.500 µg/mL. Similarly, a genomic damage was observed also in the cultures treated with the same concentrations of both compounds, except for exposure to 0.0065 and 0.0125 µg/mL. No synergistic action was observed. Finally, a significant increase in apoptotic cells was observed in cultures treated with the highest concentration of tested xenobiotics, while a significant increase in necrotic cells was observed also at the concentration of 0.250 µg/mL of both glyphosate and AMPA alone and in combination (0.125 + 0.125 µg/mL). Results of our study indicate that both glyphosate and its metabolite AMPA are able to cause genomic damage in human lymphocyte cultures, both alone and when present in equal concentrations.

3.
Technol Health Care ; 32(4): 2825-2836, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38995741

RESUMEN

BACKGROUND: The radiation released at the time of dental panoramic radiographs causes genotoxic and cytotoxic effects on epithelial cells. OBJECTIVE: This research aimed to evaluate the changes in the frequencies of micronucleated cells in patients' buccal epithelial cells following dental panoramic radiography. METHODS: 74 patients were recruited for the study who were advised for panoramic radiographs. Using a wooden spatula, the buccal epithelial cells were scraped from both cheeks before to panoramic radiation exposure and ten days after the panoramic radiation exposure. Giemsa stain was used to stain the cells, and 500 cells were scored on a slide to determine the frequency of micronuclei. To determine the difference between the frequency of micronuclei before and after radiation exposure, a paired t-test was used in the statistical analysis. RESULTS: The proportion of micronuclei cells was 0.11% before radiation exposure and 0.57% following radiation exposure after 10 days. A statistically significant increase in the frequencies of micronuclei was noted after radiation exposure values. CONCLUSION: This study revealed the genotoxicity of epithelial cells with dental panoramic radiation exposure. It is advised to reduce the use of such radiographs and to use only when there is no other diagnostic tool that is helpful or when absolutely essential.


Asunto(s)
Células Epiteliales , Pruebas de Micronúcleos , Mucosa Bucal , Radiografía Panorámica , Humanos , Radiografía Panorámica/efectos adversos , Mucosa Bucal/efectos de la radiación , Mucosa Bucal/diagnóstico por imagen , Mucosa Bucal/citología , Masculino , Femenino , Células Epiteliales/efectos de la radiación , Adulto , Persona de Mediana Edad , Micronúcleos con Defecto Cromosómico/efectos de la radiación , Adulto Joven
4.
Biochem Biophys Res Commun ; 733: 150442, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39053103

RESUMEN

INTRODUCTION: Radioprotectors help to protect the body or at least minimize the negative consequences of radiation exposure. The present study aimed to assess the radioprotective potential of Helianthus tuberosus L. polysaccharide (HTLP) in vitality and micronuclei tests. To assess the cytotoxic effects of HTLP, both vitality and MTT reductase assays were conducted. MATERIALS AND METHODS: RAW 264.7 cells viability was assessed 24 h after adding 200 µg/ml HTLP solution by staining cell cultures with propidium iodide and bis-benzimide to detect the nuclei of dead cells and the total number of cells in culture. To assess cell viability via cellular metabolic activity MTT test was used. In this work outbred 24-30 g 5-months old SHK mice have been used. Irradiation was provided with proton beams with an energy of 660 MeV at a dose rate of 80 Gy with doses 1.5 Gy for micronuclei test and 8.5 Gy for survival test. Whole body X-ray irradiation was conducted using the RUT-15 therapeutic X-ray unit with doses of 1.5 Gy for MN test and 6.5 Gy for survival. The HTLP sterile solution in dose 100 µg/animal was injected into the tail vein 15 min before X-ray or proton irradiation. RESULTS AND CONCLUSION: s: Vitality test showed no significant differences between the control group and cells treated with 200 µl of 200 µg/ml HTLP solution, though a greater variability was noted. In contrast, the MTT assay indicated enhanced cell viability in the HTLP-treated cells. HTLP does not exert any toxic effects in cell culture. Moreover, results of MTT reductase assay shows, that HTLP may enhance the cells' metabolic activity. Animals pre-treated with HTLP displayed a significant reduction in micronuclei formation, showing five times fewer micronuclei in bone marrow cells compared to the non-treated group. This comparison highlights HTLP's potential protective effect against radiation-induced chromosomal damage. HTLP treatment demonstrates a significant reduction in hazard compared to the control, indicating its protective effects against irradiation. Thus, it can be concluded that the use of HTLP increases the likelihood of animal survival under the ionizing effects of X-rays and protons. The survival analysis reveals that the HTLP-treated groups exhibit a higher survival rate compared to both the control and Cysteamine-treated groups, suggesting a significant protective effect of HTLP against irradiation, regardless of the type of irradiation (proton or X-ray) with p < 0.0001.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39054003

RESUMEN

Micronucleus (MN) cell counting emerged in 1973-1975 as a valid alternative for characterizing chromosomal damage caused by different agents. It was first described in mammals, but its application was rapidly extended to other vertebrates, mainly fish. However, it was not until 28 years later that this test was implemented in studies on reptiles. Nowadays, reptiles are found to be excellent non-target species from environmental contamination exposure and MN test has become a fundamental tool for analyzing genotoxic effects induced by various xenobiotics. In this article we provide an updated review of the application of the MN test in reptile species, from an ecotoxicological perspective. Therefore, we present (I) a bibliometric analysis of the available research on genotoxic-induced MN formation in reptile species; (II) the use of reptiles as sentinel organisms in ecotoxicological studies; and (III) the strength and weakness of the application of the MN test in this group. With this review, we aim to provide a comprehensive view on the use of the MN test in ecotoxicology and to encourage further studies involving reptile species.


Asunto(s)
Pruebas de Micronúcleos , Reptiles , Animales , Reptiles/genética , Pruebas de Micronúcleos/métodos , Mutágenos/toxicidad , Ecotoxicología/métodos , Daño del ADN/efectos de los fármacos , Especies Centinela/genética
6.
Artículo en Inglés | MEDLINE | ID: mdl-39054005

RESUMEN

Per- and polyfluoroalkyl substances (PFAS) comprise many chemicals with strong carbon-carbon and carbon-fluorine bonds and have extensive industrial applications in manufacturing several consumer products. The solid covalent bonding makes them more persistent in the environment and stays away from all types of degradation, naming them 'forever chemicals.' Zebrafish (Danio rerio) was used to evaluate the genotoxic and cytotoxic effects of legacy PFAS, Perfluorooctane sulfonate (PFOS), and its alternatives, such as Perfluoro-2-methyl-3-oxahexanoic acid ammonium (GenX) and 7H-Perfluoro-3,6-dioxa-4-methyl-octane-1-sulfonic acid (Nafion by-product 2 [NBP2]) upon single and combined exposure at an environmental concentration of 10 µg/L for 48-h. Erythrocyte micronucleus cytome assay (EMNCA) revealed an increased frequency of micronuclei (MN) in fish erythrocytes with a significant increase in NBP2-treated fish. The order of genotoxicity noticed was NBP2 > PFOS > Mixture > GenX in D. rerio. Fish exposed to PFOS and its alternatives in single and combined experiments did not cause any significant difference in nuclear abnormalities. However, PFOS and combined exposure positively inhibit cytokinesis, resulting in an 8.16 and 7.44-fold-change increase of binucleated cells. Besides, statistically, increased levels of reactive oxygen species (ROS) and malondialdehyde (MDA) content indicate oxidative stress in D. rerio. In addition, 'forever chemicals' resulted in cytotoxicity, as evident through changes in nucleus width to the erythrocyte length in NBP2 and mixture exposure groups. The findings revealed that PFAS alternative NBP2 is more toxic than PFOS in inducing DNA damage and cytotoxicity. In addition, all three tested 'forever chemicals' induced ROS and lipid peroxidation after individual and combined exposure. The present work is the first to concern the genotoxicity and cytotoxicity of 'forever chemicals' in the aquatic vertebrate D. rerio.


Asunto(s)
Ácidos Alcanesulfónicos , Daño del ADN , Fluorocarburos , Pruebas de Micronúcleos , Contaminantes Químicos del Agua , Pez Cebra , Animales , Fluorocarburos/toxicidad , Pruebas de Micronúcleos/métodos , Ácidos Alcanesulfónicos/toxicidad , Daño del ADN/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Estrés Oxidativo/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Mutágenos/toxicidad
7.
Artículo en Inglés | MEDLINE | ID: mdl-39054011

RESUMEN

The extraction and burning of coal release genotoxic pollutants, and understanding the relationship between genetic damage and the spatial distribution of residences in coal-using regions is crucial. The study aimed to conduct a spatial analysis of genotoxic damage through the of micronuclei (MNs) number and their proximity to coal mining/burning in the largest coal exploration region in Brazil. In this study, the detection of genotoxic damage was performed using the MN assay in oral cells of residents exposed to coal mining activities. Spatial analysis was conducted using QGIS 3.28.10 based on information obtained from a questionnaire administered to the population. Multiple linear regression analysis was carried out to assess the influence of the distance from residential areas to polluting sources on the number of MNs found. Additionally, Spearman's correlation was performed to identify the strength and direction of the association between the frequency of MNs and each of the polluting sources. A total of 147 MNs were quantified among all participants in the coal mining region. Notably, residents living within 2 km and 10 km of pollution sources exhibited the highest prevalence of MNs. The analysis demonstrated a significant correlation between closer proximity to pollution sources and increased MN frequency, underscoring the spatial relationship between these sources and genotoxic damage. Environmental pollutants from anthropogenic sources present a major health risk, potentially leading to irreversible damage. The spatial analysis in this study highlights the importance of targeted public policies. These policies should aim for a sustainable balance between economic development and public health, promoting effective measures to mitigate environmental impacts and protect community health.


Asunto(s)
Minas de Carbón , Micronúcleos con Defecto Cromosómico , Pruebas de Micronúcleos , Mucosa Bucal , Brasil , Humanos , Mucosa Bucal/citología , Micronúcleos con Defecto Cromosómico/estadística & datos numéricos , Micronúcleos con Defecto Cromosómico/inducido químicamente , Adulto , Masculino , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Persona de Mediana Edad , Daño del ADN , Análisis Espacial , Adulto Joven
8.
Int J Radiat Biol ; : 1-15, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39058359

RESUMEN

PURPOSE: Nowadays people are exposed to radiation due to various reasons, including natural, diagnostic, occupational or accidental exposure. High level of exposure to ionizing radiation can be fatal to human body. Synthetic drugs used to prevent radiation-induced damage are toxic in nature. Recently, Herbal drugs are being screened as an alternative due to their mechanism of action. Garcinia indica (G. indica) is one of the traditional medicinal plant which contains phytochemicals having several medicinal properties. MATERIALS AND METHODS: In this study, G. indica extract was observed for its modulatory effect against 3 Gray (Gy) gamma radiation-induced damages in human peripheral blood lymphocytes. Various concentrations of G. indica extract ranging from 1 to 25 µg/mL was added to the blood post irradiation at 0 hr. Chromosomal aberration (CA) and Cytochalasin B blocked Micronuclei Cytome (CBMN) Assay were performed as per standard procedure. RESULTS: Radiomodulatory effect of Garcinia indica fruit rind extract (GIFRE) on CA and MN formation was observed in this study. Treatment of GIFRE did not affect the mitotic index. Positive inhibition percentages for dicentrics, total chromosomal aberrations and micronuclei were observed except for one instance. CONCLUSION: Owing to the various properties of Garcinia extracts, it makes it a potential candidate to be tested for its radiomodulatory effect. Based on the results observed in this preliminary study, it could act as a radiomodulatory agent. Radiomodulatory effect of GIFRE could possibly serve it as a potential herbal medicinal alternative to current drugs. However, results of this study need to be validated on larger sample size.

9.
BMC Vet Res ; 20(1): 294, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38970005

RESUMEN

Since its identification in the vitreous humour of the eye and laboratory biosynthesis, hyaluronic acid (HA) has been a vital component in several pharmaceutical, nutritional, medicinal, and cosmetic uses. However, little is known about its potential toxicological impacts on aquatic inhabitants. Herein, we investigated the hematological response of Clarias gariepinus to nominal doses of HA. To achieve this objective, 72 adult fish were randomly and evenly distributed into four groups: control, low-dose (0.5 mg/l HA), medium-dose (10 mg/l HA), and high-dose (100 mg/l HA) groups for two weeks each during both the exposure and recovery periods. The findings confirmed presence of anemia, neutrophilia, leucopoenia, lymphopenia, and eosinophilia at the end of exposure to HA. In addition, poikilocytosis and a variety of cytomorphological disturbances were observed. Dose-dependent histological alterations in spleen morphology were observed in the exposed groups. After HA removal from the aquarium for 2 weeks, the groups exposed to the two highest doses still exhibited a notable decline in red blood cell count, hemoglobin concentration, mean corpuscular hemoglobin concentration, and an increase in mean corpuscular volume. Additionally, there was a significant rise in neutrophils, eosinophils, cell alterations, and nuclear abnormalities percentages, along with a decrease in monocytes, coupled with a dose-dependent decrease in lymphocytes. Furthermore, only the highest dose of HA in the recovered groups continued to cause a significant increase in white blood cells. White blood cells remained lower, and the proportion of apoptotic RBCs remained higher in the high-dose group. The persistence of most of the haematological and histological disorders even after recovery period indicates a failure of physiological compensatory mechanisms to overcome the HA-associated problems or insufficient duration of recovery. Thus, these findings encourage the inclusion of this new hazardous agent in the biomonitoring program and provide a specific pattern of hematological profile in HA-challenged fish. Further experiments are highly warranted to explore other toxicological hazards of HA using dose/time window protocols.


Asunto(s)
Bagres , Ácido Hialurónico , Bazo , Animales , Ácido Hialurónico/sangre , Bazo/efectos de los fármacos , Bazo/patología , Relación Dosis-Respuesta a Droga
10.
Front Genet ; 15: 1422938, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39027885

RESUMEN

Purpose: Coal mining is a vital sector in Colombia, contributing significantly to the nation's economy and the development of its regions. However, despite its importance, it has led to a gradual decline in the health of mine workers and nearby residents. While the adverse health effects of open-pit coal mining on exposed individuals have been well-documented in Colombia and globally, studies investigating genetic damage in underground coal miners are lacking. Methods: The aim of our study was to evaluate chromosomal and genotoxic damage, in peripheral blood samples from a group of underground coal miners and residents of areas exposed to coal, in the town of Samacá, Boyacá-Colombia, and in a group of unexposed individuals by using banding and molecular cytogenetic techniques, as well as cytokinesis block micronucleus assays. Results: Our results suggest that occupational exposure to coal induces chromosomal and genotoxic damage in somatic cells of underground coal miners. Chromosomal and genotoxic damage is an important step in carcinogenesis and the development of many other diseases. Our findings provide valuable insights into the effects of coal dust exposure on chromosomal integrity and genetic stability. Conclusion: Our pilot study suggests that occupational exposure to coal induces chromosomal damage in underground coal miners, highlighting the importance of validating these findings with a larger sample size. Our results highlight the need to implement prevention and protection measures, as well as educational programs for underground coal miners. Characterizing and estimating exposure risks are extremely important for the safety of people exposed occupationally and environmentally to coal and its derivatives.

11.
Mutat Res Rev Mutat Res ; 794: 108510, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39004337

RESUMEN

Micronucleus (MN) assays with buccal cells are at present widely used to investigate occupational exposures to genotoxic carcinogens. This article describes their use for the monitoring of metal exposed workers. We found in total 73 relevant articles, in the majority (97 %) increased MN and/or other nuclear anomalies were reported. Most studies were realized in South East Asia and South America. A variety of different occupations was studied including welders, electroplaters, painters, workers in battery recycling and production, tannery workers, dental technicians, miners, workers in foundries and smelters, and also subjects working in waste recycling, glass, aluminum and steel production. In many investigations the effects increased with the duration of the working period. The quality of individual studies was evaluated with a quality score tool. The number of cells was in most studies sufficient and DNA-specific stains were used. However, many studies have shortcomings, e.g. they focused solely on MN formation and did not evaluate anomalies, which provide additional information about the stability of the genetic material and acute cytotoxic effects. Only 35 % of the investigations contain quantitative information about exposures to metals and other toxicants. In 6 of these studies, correlations were observed between the concentrations of specific metals (As, Pb, Cr, Cd) in body fluids and MN frequencies. Taken together, the available data indicate that the MN assay can be used to detect chromosomal damage in metal exposed groups; furthermore, it enables also comparisons between subgroups differing in regard to their exposure and allows an estimation of the efficiency of protective measures. The exposure of workers to metals is currently controlled with chemical analytical measurements only, MN assays with buccal cells could contribute to further improve the safety at workplaces as they reflect the biological consequences including synergistic and antagonistic interactions between toxicants.

12.
Pak J Biol Sci ; 27(5): 276-282, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38840468

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
13.
Cells ; 13(11)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38891041

RESUMEN

Glufosinate-ammonium (GLA), an organophosphate herbicide, is released at high concentrations in the environment, leading to concerns over its potential genotoxic effects. However, few articles are available in the literature reporting the possible cellular and nuclear effects of this compound. We assessed, by in vitro and in vivo micronucleus assays, the genotoxicity of GLA on cultured human lymphocytes and Lymnaea stagnalis hemocytes at six concentrations: 0.010 (the established acceptable daily intake value), 0.020, 0.050, 0.100, 0.200, and 0.500 µg/mL. In human lymphocytes, our results reveal a significant and concentration-dependent increase in micronuclei frequency at concentrations from 0.100 to 0.500 µg/mL, while in L. stagnalis hemocytes, significant differences were found at 0.200 and 0.500 µg/mL. A significant reduction in the proliferation index was observed at all tested concentrations, with the only exception of 0.010 µg/mL, indicating that the exposure to GLA could lead to increased cytotoxic effects. In L. stagnalis, a significant reduction in laid eggs and body growth was also observed at all concentrations. In conclusion, we provided evidence of the genomic and cellular damage induced by GLA on both cultured human lymphocytes and a model organism's hemocytes; in addition, we also demonstrated its effects on cell proliferation and reproductive health in L. stagnalis.


Asunto(s)
Aminobutiratos , Inestabilidad Genómica , Hemocitos , Herbicidas , Linfocitos , Herbicidas/toxicidad , Aminobutiratos/farmacología , Humanos , Animales , Inestabilidad Genómica/efectos de los fármacos , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Hemocitos/efectos de los fármacos , Pruebas de Micronúcleos , Proliferación Celular/efectos de los fármacos
14.
Toxicol Mech Methods ; : 1-15, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38863169

RESUMEN

INTRODUCTION: Heavy metals (HM) and polycyclic aromatic hydrocarbons (PAHs) exposition has been associated with health problems. Therefore, this research evaluated genotoxicity induced in male mice strain CD-1 exposed to benzo[a]anthracene (B[a]A) and benzo[a]pyrene (B[a]P) and their interaction with Fe, Pb, and Al. METHODS: Groups of animals were exposed intraperitoneally to HM, PAHs, and mixtures of both. Peripheral blood samples were taken from 0 to 96 h at 24 h intervals; genotoxicity was determined by micronucleus tests and comet assay. Additionally, toxicity and viability were evaluated. RESULTS: HM and PAHs individually were genotoxic. About toxicity, only Al altered polychromatic erythrocytes number and did not change leukocytes viability. Concerning mixtures, Fe + B[a]P, Fe + B[a]A, Pb + B[a]P increased genotoxicity. There were no changes with Pb + B[a]A. Finally, Al mixtures with both PAHs damage was decreased. CONCLUSIONS: Exposure to HM and PAH caused genetic damage. Fe, Al, and B[a]A, established a genotoxic potential. Every metal can interact with PAHs in different ways. Also, the micronucleus test and the comet assay demonstrated their high capacity and reliability to determine the genotoxic potential of the compounds evaluated in this work.

15.
Eur J Nutr ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38864865

RESUMEN

PURPOSE: Magnesium is one of the most common elements in the human body and plays an important role as a cofactor of enzymes required for DNA replication and repair and many other biochemical mechanisms including sensing and regulating one-carbon metabolism deficiencies. Low intake of magnesium can increase the risk of many diseases, in particular, chronic degenerative disorders. However, its role in prevention of DNA damage has not been studied fully in humans so far. Therefore, we tested the hypothesis that magnesium deficiency either on its own or in conjunction with high homocysteine (Hcy) induces DNA damage in vivo in humans. METHODS: The present study was carried out in 172 healthy middle aged subjects from South Australia. Blood levels of magnesium, Hcy, folate and vitamin B12 were measured. Cytokinesis-Block Micronucleus cytome assay was performed to measure three DNA damage biomarkers: micronuclei (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBuds) in peripheral blood lymphocytes. RESULTS: Data showed that magnesium and Hcy are significantly inversely correlated with each other (r = - 0.299, p < 0.0001). Furthermore, magnesium is positively correlated both with folate (p = 0.002) and vitamin B12 (p = 0.007). Magnesium is also significantly inversely correlated with MN (p < 0.0001) and NPB (p < 0.0001). Individuals with low magnesium and high Hcy exhibited significantly higher frequency of MN and NPBs compared to those with high magnesium and low Hcy (p < 0.0001). Furthermore, there was an interactive effect between these two factors as well in inducing MN (p = 0.01) and NPB (p = 0.048). CONCLUSIONS: The results obtained in the present study indicate for the first time that low in vivo levels of magnesium either on its own or in the presence of high Hcy increases DNA damage as evident by higher frequencies of MN and NPBs.

16.
Methods Mol Biol ; 2825: 309-331, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38913318

RESUMEN

Across eukaryotes, genome stability is essential for normal cell function, physiology, and species survival. Aberrant expression of key genes or exposure to genotoxic agents can have detrimental effects on genome stability and contribute to the development of various diseases, including cancer. Chromosome instability (CIN), or ongoing changes in chromosome complements, is a frequent form of genome instability observed in cancer and is a driver of genetic and cell-to-cell heterogeneity that can be rapidly detected and quantitatively assessed using surrogate markers of CIN. For example, single cell quantitative imaging microscopy (QuantIM) can be used to simultaneously identify changes in nuclear areas and micronucleus formation. While changes in nuclear areas are often associated with large-scale changes in chromosome complements (i.e., ploidy), micronuclei are small extra-nuclear bodies found outside the primary nucleus that have previously been employed as a measure of genotoxicity of test compounds. Here, we present a facile QuantIM approach that allows for the rapid assessment and quantification of CIN associated phenotypes and genotoxicity. First, we provide protocols to optimize and execute CIN and genotoxicity assays. Secondly, we present the critical imaging settings, optimization steps, downstream statistical analyses, and data visualization strategies employed to obtain high quality and robust data. These approaches can be easily applied to assess the prevalence of CIN associated phenotypes and genotoxic stress for a myriad of experimental and clinical contexts ranging from direct tests to large-scale screens of various genetic contexts (i.e., aberrant gene expression) or chemical compounds. In summary, this QuantIM approach facilitates the identification of novel CIN genes and/or genotoxic agents that will provide greater insight into the aberrant genes and pathways underlying CIN and genotoxicity.


Asunto(s)
Inestabilidad Cromosómica , Daño del ADN , Análisis de la Célula Individual , Análisis de la Célula Individual/métodos , Humanos , Microscopía/métodos , Pruebas de Mutagenicidad/métodos , Núcleo Celular/metabolismo , Núcleo Celular/efectos de los fármacos , Mutágenos/toxicidad , Pruebas de Micronúcleos/métodos
17.
J Toxicol Environ Health A ; 87(18): 719-729, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-38884257

RESUMEN

Corn is the second most cultivated crop in Brazil, the number-one country in pesticide consumption. Chemical control of weeds is performed using herbicides such as S-metolachlor with pre- and post-emergence action and thus the toxicity of herbicides constitutes a matter of great concern. The present investigation aimed to examine the effects of an S-metolachlor-based herbicide on Lactuca sativa L. (lettuce) and Zea mays L. (maize) utilizing various bioassays. The test solutions were prepared from commercial products containing the active ingredient. Seeds from the plant models were exposed in petri dishes and maintained under biochemical oxygen demand (BOD) at 24°C. Distilled water was negative and aluminium positive control. Macroscopic analyses (germination and growth) were conducted for both plant species, and microscopic analysis (cell cycle and chromosomal alterations) were performed for L. sativa root tip cells. Detrimental interference of S-metolachlor-based herbicide was noted with lettuce for all parameters tested reducing plant germination by over 50% and the germination speed by over 45% and showing a significant decrease in mitotic index, from 16.25% to 9,28% even on the lowest concentration tested. In maize, there was no significant interference in plant germination; however, speed of germination was significantly hampered, reaching a 51.22% reduction for the highest concentration tested. Data demonstrated that the herbicide was toxic as evidenced by its phyto- and cytotoxicity in L. sativa L. and Z. mays L.


Asunto(s)
Acetamidas , Herbicidas , Lactuca , Zea mays , Zea mays/efectos de los fármacos , Herbicidas/toxicidad , Lactuca/efectos de los fármacos , Lactuca/crecimiento & desarrollo , Acetamidas/toxicidad , Germinación/efectos de los fármacos , Semillas/efectos de los fármacos , Semillas/crecimiento & desarrollo
18.
Bioessays ; 46(8): e2400066, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38837436

RESUMEN

The Three Prime Repair Exonuclease 1 (TREX1) has been implicated in several pathologies characterized by chronic and inborn inflammation. Aberrant innate immunity caused by DNA sensing through the cGAS-STING pathway has been proposed to play a major role in the etiology of these interferonopathies. However, the molecular source of this DNA sensing and the possible involvement of TREX1 in genome (in)stability remains poorly understood. Recent findings reignite the debate about the cellular functions performed by TREX1 nuclease, notably in chromosome biology and stability. Here I put into perspective recent findings that suggest that TREX1 is at the crossroads of DNA damage response and inflammation in different pathological contexts.


Asunto(s)
Exodesoxirribonucleasas , Inestabilidad Genómica , Fosfoproteínas , Exodesoxirribonucleasas/metabolismo , Exodesoxirribonucleasas/genética , Humanos , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Animales , Daño del ADN , Citosol/metabolismo , Inmunidad Innata/genética , Inflamación/genética , Reparación del ADN/genética
19.
Artículo en Inglés | MEDLINE | ID: mdl-38821667

RESUMEN

Hairdressers are constantly occupationally exposed to many chemicals have the potential to cause allergies and carcinogenic effects, act as skin and eye irritants and induce oxidative stress and DNA damage. This study aimed to evaluate occupation-induced genotoxicity based on the presence of micronucleus (MN) and other nuclear anomalies in urothelial cells and measure oxidative DNA damage based on the 8-hydroxy-2'-deoxyguanosine level in the urine of Turkish hairdressers. Originality of this study comes from that there was no study on MN and other nuclear anomalies frequencies and oxidative DNA damage in urine samples of hairdressers in the literature. The mean±standard deviation frequency (‰) of micronucleated (MNed) cells was higher in the hairdresser group (n=56) (4.81±7.87, p<0.001) than in the control group (n=56) (0.93±1.85). Nuclear buds were not observed in either group. While the frequency of basal cells was higher in the control group (446.6±106.21) than in the hairdresser group (367.78±101.51, p<0.001), the frequency of binuclear, karyolytic, pycnotic and karyorrhectic cells were higher in the hairdresser group (0.41±0.80, p<0.001; 438.02±118.27, p<0.001; 0.43±0.76, p<0.001; and 47.27±28.40, p<0.001) than in the control group (0.04±0.27, 358.57±95.71, 0.05±0.23 and 24.41±14.50). Condensed chromatins were observed only in the hairdresser group. Specific gravity adjusted 8-hydroxy-2'-deoxyguanosine level was statistically lower in the hairdresser group (908.21±403.25 ng/mL-SG) compared to the control group (1003.09±327.09 ng/mL-SG) (p=0.024). No significant correlation was found between the 8-hydroxy-2'-deoxyguanosine level and the frequency MN. The amount of formaldehyde released during Brazilian keratin treatment was higher than the American Conference of Governmental Industrial Hygienists -Threshold Limit Value (ACGIH-TLV; 0.1 ppm). Similarly, the amount of ethyl acetate released in three salons was above the recommended limit (400 ppm). These findings suggest that hairdressers have an increased risk of genotoxicity and cytotoxicity owing to occupational exposure, regardless of age, working hours, smoking and alcohol consumption.


Asunto(s)
8-Hidroxi-2'-Desoxicoguanosina , Daño del ADN , Desoxiguanosina , Micronúcleos con Defecto Cromosómico , Pruebas de Micronúcleos , Exposición Profesional , Urotelio , Humanos , 8-Hidroxi-2'-Desoxicoguanosina/orina , Exposición Profesional/efectos adversos , Adulto , Turquía , Urotelio/efectos de los fármacos , Urotelio/patología , Urotelio/metabolismo , Urotelio/citología , Desoxiguanosina/análogos & derivados , Desoxiguanosina/orina , Masculino , Micronúcleos con Defecto Cromosómico/inducido químicamente , Daño del ADN/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Persona de Mediana Edad , Femenino , Adulto Joven , Estudios de Casos y Controles , Núcleo Celular/efectos de los fármacos
20.
Food Chem Toxicol ; 189: 114749, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38768938

RESUMEN

Emodin is an anthraquinone secondary metabolite produced by several species of plants and fungi. Emodin is known for its pharmacological versatility, and, in the textile industry, for its good dyeing properties. However, its use in the textile industry can result in the formation and disposal of large volumes of wastewater. Emodin mutagenicity has been shown in bacteria and in human cells, but little is known about its possible toxic, genotoxic, or mutagenic effects in aquatic organisms. We have evaluated the eco/genotoxicity of emodin to aquatic organisms. Emodin was toxic to Daphnia similis (EC50 = 130 µg L-1) and zebrafish embryos (LC50 = 25 µg L-1). No toxicity was observed for Raphidocelis subcapitata, Ceriodaphnia dubia, or Parhyale hawaiensis. Additional biochemistry/molecular studies are needed to elucidate the toxic/mutagenic pathways of emodin in aquatic organisms. The PNEC value for emodin was 0.025 µg L-1. In addition to mutagenicity in the Salmonella/microsome assay, emodin was mutagenic in the micronucleus assay in the amphipod P. hawaiensis. Among the anthraquinone dyes tested to date, natural or synthetic, emodin was the most toxic to aquatic species.


Asunto(s)
Colorantes , Daphnia , Emodina , Pruebas de Mutagenicidad , Contaminantes Químicos del Agua , Pez Cebra , Emodina/toxicidad , Emodina/análogos & derivados , Animales , Colorantes/toxicidad , Daphnia/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Organismos Acuáticos/efectos de los fármacos , Mutágenos/toxicidad , Pruebas de Micronúcleos , Antraquinonas/toxicidad , Antraquinonas/química , Embrión no Mamífero/efectos de los fármacos
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