•C60 fullerene can induce DNA damage.•C60 fullerene does not affect the reproductive system and embryogenesis.•Activation of DNA-repair might decrease the effects of C60 fullerene at the organismal ...level.
Fullerenes have attracted attention since their discovery as structural units of complex carbon nanostructures capable of transporting drugs and macromolecules. As such artificial nanomaterials are applied in biology and medicine, they are routinely scrutinized for their effects on living organisms. The results of such studies range from direct destabilizing effects on DNA molecules to amelioration of the toxic effects of known genotoxic agents. We tested the effect of buckminsterfullerene (C60) on Drosophila melanogaster at DNA, tissue and organism levels. The water-soluble pristine C60 fullerene at the concentration of 20 μg/ml and 40 μg/ml leads to the activation of the mus209 gene in D. melanogaster larvae salivary glands, which can indicate higher levels of DNA damage. However, the absence of effects at the cell and organismal level could be explained by the activation of repair systems or by active elimination of damaged cells.
Understanding the mode-of-action (MOA) of genotoxic compounds and differentiating between direct DNA interaction and indirect genotoxicity is crucial for their reliable safety assessment. ToxTracker ...is a stem cell-based reporter assay that detects activation of various cellular responses that are associated with genotoxicity and cancer. ToxTracker consists of 6 different GFP reporter cell lines that can detect the induction of DNA damage, oxidative stress, and protein damage in a single test. The assay can thereby provide insight into the MOA of compounds. Genotoxicity is detected in ToxTracker by activation of 2 independent GFP reporters. Activation of the Bscl2-GFP reporter is associated with induction of DNA adducts and subsequent inhibition of DNA replication and the Rtkn-GFP reporter is activated following the formation of DNA double-strand breaks. Here, we show that the differential activation of these 2 genotoxicity reporters could be used to further differentiate between a DNA reactive and clastogenic or a non-DNA-reactive aneugenic MOA of genotoxic compounds. For further classification of aneugenic and clastogenic compounds, the ToxTracker assay was extended with cell cycle analysis and aneuploidy assessment. The extension was validated using a selection of 16 (genotoxic) compounds with a well-established MOA. Furthermore, indirect genotoxicity related to the production of reactive oxygen species was investigated using the DNA damage and oxidative stress ToxTracker reporters in combination with different reactive oxygen species scavengers. With these new extensions, ToxTracker was able to accurately classify compounds as genotoxic or nongenotoxic and could discriminate between DNA-reactive compounds, aneugens, and indirect genotoxicity caused by oxidative stress.
Engineered nanomaterials (ENMs) refer to a relatively novel class of materials that are increasingly prevalent in various consumer products and industrial applications – most notably for their ...superlative physicochemical properties when compared with conventional materials. However, consumer products inevitably degrade over the course of their lifetime, releasing ENMs into the environment. These ENMs undergo physicochemical transformations and subsequently accumulate in the environment, possibly leading to various toxic effects. As a result, a significant number of studies have focused on identifying the possible transformations and environmental risks of ENMs, with the objective of ensuring a safe and responsible application of ENMs in consumer products. This review aims to consolidate the results from previous studies related to each stage of the pathway of ENMs from being embodied in a product to disintegration/transformation in the environment. The scope of this work was defined to include the five most prevalent ENMs based on recent projected production market data, namely: nTiO2, nSiO2, nZnO, carbon nanotubes, and nAg. The review focuses on: (i) models developed to estimate environmental concentrations of ENMs; (ii) the possible physicochemical transformations; (iii) cytotoxicity and genotoxicity effects specific to each ENM selected; and (iv) a discussion to identify potential gaps in the studies conducted and recommend areas where further investigation is warranted.
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•Transformations and toxicity of five most prevalent nanomaterials are discussed.•Aggregation, surface charge change and dissolution are the transformations observed.•Oxidative stress and ROS generation leads to cytotoxicity and genotoxicity.•DNA breakage, chromosomal aberration & micronuclei are notable genotoxic effects.•The research gaps are summarised and possible research directions are recommended.
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.
•Environmental contaminants induce MN and NA formation in reptiles.•reptiles are excellent non-target species for environmental contamination.•MN test applied to 32 out of the 12.060 reptile species worldwide.•Crocodilians are the reptile group most studied (11.11 % of total).•The main pollutants reported are pesticides, followed by heavy metals.
During almost 40 years of use, the micronucleus assay (MN) has become one of the most popular methods to assess genotoxicity of different chemical and physical factors, including ionizing ...radiation-induced DNA damage. In this minireview, we focus on the position of MN among the other genotoxicity tests, its usefulness in different applications and visibility by international organizations, such as International Atomic Energy Agency, Organization for Economic Co-operation and Development and International Organization for Standardization. In addition, the mechanism of micronuclei formation is discussed. Finally, foreseen directions of the MN development are pointed, such as automation, buccal cells MN and chromothripsis phenomenon.
Aspartame: A review of genotoxicity data Kirkland, David; Gatehouse, David
Food and chemical toxicology,
October 2015, 2015-Oct, 2015-10-00, 20151001, Volume:
84
Journal Article
Peer reviewed
Open access
Aspartame is a methyl ester of a dipeptide of aspartic acid and phenylalanine. It is 200× sweeter than sucrose and is approved for use in food products in more than 90 countries around the world. ...Aspartame has been evaluated for genotoxic effects in microbial, cell culture and animal models, and has been subjected to a number of carcinogenicity studies. The in vitro and in vivo genotoxicity data available on aspartame are considered sufficient for a thorough evaluation. There is no evidence of induction of gene mutations in a series of bacterial mutation tests. There is some evidence of induction of chromosomal damage in vitro, but this may be an indirect consequence of cytotoxicity. The weight of evidence from in vivo bone marrow micronucleus, chromosomal aberration and Comet assays is that aspartame is not genotoxic in somatic cells in vivo. The results of germ cell assays are difficult to evaluate considering limited data available and deviations from standard protocols. The available data therefore support the conclusions of the European Food Safety Authority (EFSA) that aspartame is non-genotoxic.
•Data from multiple in vitro and in vivo genotoxicity studies with aspartame have been reviewed.•There is no evidence of induction of gene mutations in a series of bacterial mutation tests.•Reported increases in chromosomal damage in vitro have not been confirmed in vivo.•The data support EFSA's conclusion that aspartame is non-genotoxic.
The pollution by heavy metals poses a serious threat to the aquatic environment and to the organisms if the concentration of heavy metals in the environment exceeds the safe limits. Due to their ...non-biodegradable and long persistence nature in the environment, heavy metals cause toxicity in fish by producing oxygen reactive species through oxidizing radical production. In this review, we investigated the effects of heavy metals on fish physiology with special emphasis on hemato-biochemical properties, immunological parameters especially hormones and enzymes, histopathology of different major organs and underlying molecular mechanisms. All those parameters are significantly affected by heavy metal exposure and are found to be important bio-monitoring tools to assess heavy metal toxicity. Hematological and biochemical alterations have been documented including cellular and nuclear abnormalities in different fish species exposed to different concentrations of heavy metals. Major fish organs (gills, liver, kidneys) including intestine, muscles showed different types of pathology specific to organs in acute and chronic exposure to different heavy metals. This study also revealed the expression of different genes involved in oxidative stress and detoxification of heavy metals. In a nutshell, this article shades light on the manipulation of fish physiology by the heavy metals and sought attention in the prevention and maintenance of aquatic environments particularly from heavy metals contaminations.
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•Heavy metal in water cause toxicity to fish is a global concern.•Describe mode of actions of heavy metals in living tissues.•Provides a general view on the effects of heavy metals on fish physiology.
Amantadine (AMA) is a useful drug in neuronal disorders, but few studies have been performed to access its toxicological profile. Conversely, doxorubicin (Dox) is a well-known antineoplastic drug ...that has shown neurotoxic effects leading to cognitive impairment. The aims of this study are to evaluate the cytotoxic, genotoxic, and mutagenic effects of AMA, as well as its possible protective actions against deleterious effects of Dox. The Salmonella/microsome assay was performed to assess mutagenicity while cytotoxicity and genotoxicity were evaluated in SH-SY5Y cells using MTT and comet assays. Possible modulating effects of AMA on the cytotoxicity, genotoxicity, and mutagenicity induced by Dox were evaluated through cotreatment procedures. Amantadine did not induce mutations in the Salmonella/microsome assay and decreased Dox-induced mutagenicity in the TA98 strain. AMA reduced cell viability and induced DNA damage in SH-SY5Y cells. In cotreatment with Dox, AMA attenuated the cytotoxicity of Dox and showed an antigenotoxic effect. In conclusion, AMA does not induce gene mutations, although it has shown a genotoxic effect. Furthermore, AMA decreases frameshift mutations induced by Dox as well as the cytotoxic and genotoxic effects of Dox in SH-SY5Y cells, suggesting that AMA can interfere with Dox mutagenic activity and attenuate its neurotoxic effects.
•Amantadine increases strand break DNA in SH-SY5Y cells.•Frameshift mutations induced by doxorubicin are inhibited for amantadine.•The combination amantadine plus doxorubicin increases the cell viability of SH-SY5Y cells.•Amantadine decreases the genotoxicity of doxorubicin in SH-SY5Y cells.
Electronics waste is solid waste that accumulates because of the short lifespan of many types of electronic equipment. Most electronics waste ends up in landfills, whereas some is recycled. In the ...occupied Palestinian territory, the village of Idhna in the Hebron District is a large site for recycling electronics waste (much of this waste originates from Israel). The aim of this study was to evaluate the effects of electronics waste on human DNA damage and chromosome breaks.
In this cross-sectional study, we recruited non-smoker individuals with direct exposure to electronics waste either because they were employed in the workshops or resident in Idhna. Control participants were selected to match the test sample in age and sex distribution, were recruited from Bethlehem and Al-Aizariya (Bethany). Blood samples in sodium heparin were evaluated for DNA damage using the COMET assay, whereas chromosome aberrations were tested by using conventional cytogenetic techniques.
46 participants were included in the test sample, and 16 participants were included in the control sample. Participants in the test sample had an average of 3·77 chromosomes with aberrations (SD 2·5), whereas participants in the control group had an average of 0·75 chromosomes with aberrations (SD 0·61). The frequency of chromatid and chromosome breaks, formation of rings, and total chromosome aberrations was statistically different between exposed and control samples, but no difference was observed between exposed and controls for the incidence of dicenterics and tetraploidy. Results of the Comet assay showed a significant difference in DNA damage between exposed and control participants (p<0·05). No difference between the workers and the residents living in the area was noted (p<0·05).
Exposure to recycled electronics waste in Idhna has potentially adverse health consequences. This is the second study of this kind in the occupied Palestinian territories. Hammad and Qumsiyeh (2013) have previously shown substantial genotoxic effects of Israeli industrial settlement discharge on human populations in Salfit (northern West Bank). Considering increased incidence of cancer and congenital birth defects in the southern part of the West Bank, these findings were important in promoting the case for mitigation measures, which are now under way.
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