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PloS One 2020In recent years, chronic degenerative diseases such as certain types of cancers, are becoming an evident issue. DNA damage has been for long recognized as a causal...
In recent years, chronic degenerative diseases such as certain types of cancers, are becoming an evident issue. DNA damage has been for long recognized as a causal factor for cancer development because mutations or chromosomal aberrations affect oncogenes and tumor suppressor genes leading cells to malignant transformation and to the subsequent cancerous growth. Medicinal plants are often used for the prevention or treatment of various diseases with great scientific interest. Among the medicinal plants distributed in the Mediterranean region, Fraxinus angustifolia Vahl. has been used in traditional medicine for its remarkable curative properties. However, in spite of this popularity, little works have been performed on the activity so that further studies should be performed to investigate in depth the antimutagenic, antigenotoxic and antiproliferative activities of the plant. Thus, the present study was aimed to the evaluation of the potential antimutagenic, antigenotoxic and antiproliferative properties of leaves and stem bark extracts of this well-known tree. Antimutagenic activity was evaluated by Salmonella mutagenicity assay in Salmonella typhimurium TA98 and TA100 strains. The antigenotoxic potential was assessed by umu test in the strain of S. typhimurium TA1535/pSK1002. Antiproliferative activity was studied on human hepatoblastoma (HepG-2) and on breast adenocarcinoma (MCF-7) cell lines by MTT assay. Furthermore, the antiproliferative activity observed on cancer cells was compared with that on the human normal-like fibroblasts (TelCOFS02MA) and the selectivity index was calculated to understand if extracts were able to exert selective toxicity towards cancer cells. Moreover, phenolic compounds are plant substances with a large spectrum of biochemical activities with antioxidant, antimutagenic and anticarcinogenic effects. Based on the strong evidence of biological activities of phenolic compounds, the study was focused on the determination of total phenolics and flavonoids contents, and the phytochemical composition of the extracts assessed by LC/MS. The ethanol extracts of both leaves and stem barks showed significant from moderate to strong antimutagenic and antigenotoxic effects. In addition, selective cytotoxicity towards cancer cells was shown by ethanolic leaves extract and aqueous/chloroform leaves and stem bark extracts. The latter showed high levels of total phenolic contents among all the other extracts. Identified phenylethanoids (calceolariosides, verbascoside) and secoiridoids (oleuropein and ligstroside) could be responsible for the demonstrated broad spectrum of healthy properties.
Topics: Antimutagenic Agents; Cell Proliferation; Fraxinus; Hep G2 Cells; Humans; MCF-7 Cells; Mutagens; Plant Bark; Plant Extracts; Plant Leaves
PubMed: 32298276
DOI: 10.1371/journal.pone.0230690 -
Proceedings of the National Academy of... Jan 2021Mutagenic compounds are a potent source of human disease. By inducing genetic instability, they can accelerate the evolution of human cancers or lead to the development...
Mutagenic compounds are a potent source of human disease. By inducing genetic instability, they can accelerate the evolution of human cancers or lead to the development of genetically inherited diseases. Here, we show that in addition to genetic mutations, mutagens are also a powerful source of transcription errors. These errors arise in dividing and nondividing cells alike, affect every class of transcripts inside cells, and, in certain cases, greatly exceed the number of mutations that arise in the genome. In addition, we reveal the kinetics of transcription errors in response to mutagen exposure and find that DNA repair is required to mitigate transcriptional mutagenesis after exposure. Together, these observations have far-reaching consequences for our understanding of mutagenesis in human aging and disease, and suggest that the impact of DNA damage on human physiology has been greatly underestimated.
Topics: DNA Damage; DNA Repair; DNA Replication; Humans; Mutagenesis; Mutagens; Mutation; Nucleic Acid Amplification Techniques; Transcription, Genetic
PubMed: 33443141
DOI: 10.1073/pnas.2004077118 -
Proceedings of the National Academy of... Sep 2019
Topics: DNA Transposable Elements; HSP70 Heat-Shock Proteins; Molecular Chaperones; Mutagenicity Tests; Mutagens
PubMed: 31434787
DOI: 10.1073/pnas.1912725116 -
Environment International Jan 2019Landfill leachate is a complex mixture characterized by high toxicity and able to contaminate soils and waters surrounding the dumpsite, especially in developing... (Review)
Review
Landfill leachate is a complex mixture characterized by high toxicity and able to contaminate soils and waters surrounding the dumpsite, especially in developing countries where engineered landfills are still rare. Leachate pollution can severely damage natural ecosystems and harm human health. Traditionally, the hazard assessment of leachate is based on physicochemical characterization but the toxicity is not considered. In the last few decades, different bioassays have been used to assess the toxicity of this complex matrix, including human-related in vitro models. This article reviews the cell bioassays successfully used for the risk assessment of leachate and to evaluate the efficiency of toxicity removal of several processes for detoxification of this wastewater. Articles from 2003 to 2018 are covered, focusing mainly on studies that used human cell lines, highlighting the usefulness and adequacy of in vitro models for assessing the hazard involved with exposure to leachate, particularly as an integrative supporting tool for chemical-based risk assessment. Leachate is generally toxic, mutagenic, genotoxic and estrogenic in vitro, and these effects can be measured in the cells exposed to already low concentrations, confirming the serious hazard of this wastewater for human health.
Topics: Animals; Biological Assay; Humans; Mutagens; Refuse Disposal; Water Pollutants, Chemical
PubMed: 30448364
DOI: 10.1016/j.envint.2018.11.024 -
Environmental and Molecular Mutagenesis Mar 2021The rodent Pig-a assay is a flow cytometric, phenotype-based method used to measure in vivo somatic cell mutation. An Organization for Economic Co-operation and... (Review)
Review
The rodent Pig-a assay is a flow cytometric, phenotype-based method used to measure in vivo somatic cell mutation. An Organization for Economic Co-operation and Development (OECD) test guideline is currently being developed to support routine use of the assay for regulatory purposes (OECD project number 4.93). This article provides advice on best practices for designing and conducting rodent Pig-a studies in support of evaluating test substance safety, with a focus on the rat model. Various aspects of assay conduct, including laboratory proficiency, minimum number of animals per dose group, preferred treatment and blood sampling schedule, and statistical analysis are described.
Topics: Animals; Biological Assay; Flow Cytometry; Male; Mutagenicity Tests; Mutagens; Mutation; Rats; Reticulocytes; Rodentia
PubMed: 33608913
DOI: 10.1002/em.22427 -
Chemical Research in Toxicology Dec 2022A weighted chemical coexpression network analysis (WCCNA) was utilized to identify chemicals co-modulated to variable burning of anthropogenic materials and to link...
A weighted chemical coexpression network analysis (WCCNA) was utilized to identify chemicals co-modulated to variable burning of anthropogenic materials and to link chemicals to biological responses (lung toxicity and mutagenicity). Polyaromatic hydrocarbons (PAHs) were co-modulated with increased concentrations in flaming smoke particulate matter (PM) from the burning of plastic-containing materials and showed significant association with increased neutrophil influx, cytokine levels, and mutagenicity. Inorganic elements were co-modulated with increased concentrations in flaming plywood and cardboard smoke PM and showed significant association with increased protein and albumin levels. This study shows the potential for using a computational network analysis to identify and prioritize hazardous chemical components within complex environmental mixtures and provides guidance on key chemical tracers required for intervention research to protect public health from the exposure.
Topics: Particulate Matter; Smoke; Air Pollutants; Nicotiana; Mutagens
PubMed: 36373932
DOI: 10.1021/acs.chemrestox.2c00270 -
International Journal of Molecular... Jan 2024Numerous studies have shown that oxidative modifications of guanine (7,8-dihydro-8-oxoguanine, 8-oxoG) can affect cellular functions. 7,8-Dihydro-8-oxoadenine (8-oxoA)... (Review)
Review
Numerous studies have shown that oxidative modifications of guanine (7,8-dihydro-8-oxoguanine, 8-oxoG) can affect cellular functions. 7,8-Dihydro-8-oxoadenine (8-oxoA) is another abundant paradigmatic ambiguous nucleobase but findings reported on the mutagenicity of 8-oxoA in bacterial and eukaryotic cells are incomplete and contradictory. Although several genotoxic studies have demonstrated the mutagenic potential of 8-oxoA in eukaryotic cells, very little biochemical and bioinformatics data about the mechanism of 8-oxoA-induced mutagenesis are available. In this review, we discuss dual coding properties of 8-oxoA, summarize historical and recent genotoxicity and biochemical studies, and address the main protective cellular mechanisms of response to 8-oxoA. We also discuss the available structural data for 8-oxoA bypass by different DNA polymerases as well as the mechanisms of 8-oxoA recognition by DNA repair enzymes.
Topics: Animals; Adenine; DNA-Directed DNA Polymerase; Oxidative Stress; DNA Damage; Mutagens; Mammals; DNA Repair
PubMed: 38279342
DOI: 10.3390/ijms25021342 -
Mutation Research. Genetic Toxicology... Dec 2018The lymphocyte Cytokinesis-Block Micronucleus (CBMN) assay was originally developed for the measurement of micronuclei (MN) exclusively in binucleated (BN) cells, which... (Review)
Review
The lymphocyte Cytokinesis-Block Micronucleus (CBMN) assay was originally developed for the measurement of micronuclei (MN) exclusively in binucleated (BN) cells, which represent the population of cells that can express MN because they completed nuclear division. Recently the assay has evolved into a comprehensive cytome method to include biomarkers that measure chromosomal instability and cytotoxicity by quantification of nuclear buds (NBUDs), nucleoplasmic bridges (NPBs) and apoptotic/necrotic cells. Furthermore, enumeration of mono- and polynucleated cells allows for computation of the nuclear division index (NDI) to assess mitotic activity. Typically performed by manual microscopy, the CBMN cytome assay is laborious and subject to scorer bias and fatigue, leading to inter- and intra-scorer variability. Automated microscopy and conventional flow cytometry methods have been developed to automate scoring of the traditional and cytome versions of the assay. However, these methods have several limitations including the requirement to create high-quality microscope slides, lack of staining consistency and sub-optimal nuclear/cytoplasmic visualization. In the case of flow cytometry, stripping of the cytoplasmic membrane makes it impossible to measure MN in BN cells, calculate the NDI or to quantify apoptotic or necrotic cells. Moreover, the absence of cellular visualization using conventional flow cytometry, makes it impossible to quantify NBUDs and NPBs. In this review, we propose that imaging flow cytometry (IFC), which combines high resolution microscopy with flow cytometry, may overcome these limitations. We demonstrate that by using IFC, images from cells in suspension can be captured, removing the need for microscope slides and allowing visualization of intact cytoplasmic membranes and DNA content. Thus, mono-, bi- and polynucleated cells with and without MN can be rapidly and automatically identified and quantified. Finally, we present high-resolution cell images containing NBUDs and NPBs, illustrating that IFC possesses the potential for completely automated scoring of all components of the CBMN cytome assay.
Topics: Apoptosis; Biomarkers; Cell Nucleus; Cytokinesis; DNA Damage; Environmental Exposure; Flow Cytometry; Humans; Lymphocytes; Micronucleus Tests; Mutagens
PubMed: 30389163
DOI: 10.1016/j.mrgentox.2018.05.003 -
Particle and Fibre Toxicology Dec 2021Open burning of anthropogenic sources can release hazardous emissions and has been associated with increased prevalence of cardiopulmonary health outcomes. Exposure to...
BACKGROUND
Open burning of anthropogenic sources can release hazardous emissions and has been associated with increased prevalence of cardiopulmonary health outcomes. Exposure to smoke emitted from burn pits in military bases has been linked with respiratory illness among military and civilian personnel returning from war zones. Although the composition of the materials being burned is well studied, the resulting chemistry and potential toxicity of the emissions are not.
METHODS
Smoke emission condensates from either flaming or smoldering combustion of five different types of burn pit-related waste: cardboard; plywood; plastic; mixture; and mixture/diesel, were obtained from a laboratory-scale furnace coupled to a multistage cryotrap system. The primary emissions and smoke condensates were analyzed for a standardized suite of chemical species, and the condensates were studied for pulmonary toxicity in female CD-1 mice and mutagenic activity in Salmonella (Ames) mutagenicity assay using the frameshift strain TA98 and the base-substitution strain TA100 with and without metabolic activation (S9 from rat liver).
RESULTS
Most of the particles in the smoke emitted from flaming and smoldering combustion were less than 2.5 µm in diameter. Burning of plastic containing wastes (plastic, mixture, or mixture/diesel) emitted larger amounts of particulate matter (PM) compared to other types of waste. On an equal mass basis, the smoke PM from flaming combustion of plastic containing wastes caused more inflammation and lung injury and was more mutagenic than other samples, and the biological responses were associated with elevated polycyclic aromatic hydrocarbon levels.
CONCLUSIONS
This study suggests that adverse health effects of burn pit smoke exposure vary depending on waste type and combustion temperature; however, burning plastic at high temperature was the most significant contributor to the toxicity outcomes. These findings will provide a better understanding of the complex chemical and combustion temperature factors that determine toxicity of burn pit smoke and its potential health risks at military bases.
Topics: Air Pollutants; Animals; Female; Incineration; Lung; Mice; Mutagenicity Tests; Mutagens; Particulate Matter; Rats
PubMed: 34915899
DOI: 10.1186/s12989-021-00435-w -
Scientific Reports May 2022Synacinn is a standardized polyherbal extract formulated for the treatment of diabetes mellitus and its complications. This study aims to assess the mutagenicity...
Synacinn is a standardized polyherbal extract formulated for the treatment of diabetes mellitus and its complications. This study aims to assess the mutagenicity potential of Synacinn by Ames assay and in vivo bone marrow micronucleus (MN) test on Sprague Dawley rat. Human ether-a-go-go-related gene (hERG) assay and Functional Observation Battery (FOB) were done for the safety pharmacology tests. In the Ames assay, Dose Range Finding (DRF) study and mutagenicity assays (+/- S9) were carried out. For the MN test, a preliminary and definitive study were conducted. In-life observations and number of immature and mature erythrocytes in the bone marrow cells were recorded. The hERG assay was conducted to determine the inhibitory effect on hERG potassium channel current expressed in human embryonic kidney cells (HEK293). FOB tests were performed orally (250, 750, and 2000 mg/kg) on Sprague Dawley rats. Synacinn is non-mutagenic against all tested strains of Salmonella typhimurium and did not induce any clastogenicity in the rat bone marrow. Synacinn also did not produce any significant inhibition (p ≤ 0.05) on hERG potassium current. Synacinn did not cause any neurobehavioural changes in rats up to 2000 mg/kg. Thus, no mutagenicity, cardiotoxicity and neurotoxicity effects of Synacinn were observed in this study.
Topics: Animals; HEK293 Cells; Humans; Hypoglycemic Agents; Mutagenicity Tests; Mutagens; Rats; Rats, Sprague-Dawley
PubMed: 35505003
DOI: 10.1038/s41598-022-11243-3