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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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.
Mechanisms of chromium-induced toxicity DesMarias, Thomas Liborio; Costa, Max
Current opinion in toxicology,
April 2019, 2019-04-00, 20190401, Letnik:
14
Journal Article
Recenzirano
Odprti dostop
Chromium is a pervasive environmental contaminant that is of great importance because of its toxicity. Hexavalent chromium is a classified group 1 carcinogen with multiple complex mechanisms by which ...it triggers cancer development. Increased levels of oxidative stress, chromosome breaks, and DNA adduct formation are some of the major mechanisms by which Cr(VI) causes cellular damage. Trivalent chromium is another species of chromium that is described as a nonessential metal and is used in nutritional supplementation. Evidence on nutritional benefit is conflicting, which could suggest that humans absorb enough Cr(III) from diet alone and that extra supplementation is not necessary. This review highlights the differences between Cr(VI) and Cr(III) from a chemical and toxicological perspective, describes shortcomings in nutritional research of Cr(III), and explains the multiple mechanisms by which Cr(VI) is involved in the process of carcinogenesis.
Multidrug resistance of the pathogenic microorganisms to the antimicrobial drugs has become a major impediment toward successful diagnosis and management of infectious diseases. Recent advancements ...in nanotechnology-based medicines have opened new horizons for combating multidrug resistance in microorganisms. In particular, the use of silver nanoparticles (AgNPs) as a potent antibacterial agent has received much attention. The most critical physico-chemical parameters that affect the antimicrobial potential of AgNPs include size, shape, surface charge, concentration and colloidal state. AgNPs exhibits their antimicrobial potential through multifaceted mechanisms. AgNPs adhesion to microbial cells, penetration inside the cells, ROS and free radical generation, and modulation of microbial signal transduction pathways have been recognized as the most prominent modes of antimicrobial action. On the other side, AgNPs exposure to human cells induces cytotoxicity, genotoxicity, and inflammatory response in human cells in a cell-type dependent manner. This has raised concerns regarding use of AgNPs in therapeutics and drug delivery. We have summarized the emerging endeavors that address current challenges in relation to safe use of AgNPs in therapeutics and drug delivery platforms. Based on research done so far, we believe that AgNPs can be engineered so as to increase their efficacy, stability, specificity, biosafety and biocompatibility. In this regard, three perspectives research directions have been suggested that include (1) synthesizing AgNPs with controlled physico-chemical properties, (2) examining microbial development of resistance toward AgNPs, and (3) ascertaining the susceptibility of cytoxicity, genotoxicity, and inflammatory response to human cells upon AgNPs exposure.
Toxic contaminants, including pesticides, microplastics, and heavy metals, have a significant impact on aquatic life and other aquatic species. These pollutants come from anthropogenic sources such ...as crop growing, industrial operations, effluent, residential wastewater, and leaching, as well as environmental events like storms, floods, and seismic processes. Pesticides, particularly pesticides, have been shown to have detrimental effects on aquatic ecology, causing decreased growth, restricted larvae and embryo development, and dysfunction in primary organs like the gill, liver, kidney, and gonad. Genotoxicity from pesticide exposure raises safety concerns, as prolonged exposure can lead to oxidative stress, mutagenicity, and cellular apoptosis. Pesticide exposure can lead to elevated levels, even without measurable concentrations in biological matrices. The toxicity of pesticides directly affects aquatic life, leading to high mortality rates or the complete elimination of species that serve as their food source.To maintain the well-being of aquatic organisms, particularly fish, and protect aquatic ecosystems, it is crucial to investigate safe, acceptable, and efficient alternatives to pesticides. In this study, we focuses on the hematological, biochemical, and histopathological changes induced by pesticide exposure and highlights strategies for mitigating the adverse impacts of pesticides on fish. Further investigation is needed to determine species suitability for toxicity detection, an essential aspect of monitoring aquatic environments for agricultural pesticides.
Cannabidiol (CBD), a naturally occurring cyclic terpenoid found in Cannabis sativa L., is renowned for its diverse pharmacological benefits. Marketed as a remedy for various health issues, CBD ...products are utilized by patients as a supplementary therapy or post-treatment failure, as well as by healthy individuals seeking promised advantages. Despite its widespread use, information regarding potential adverse effects, especially genotoxic properties, is limited. The present study is focused on the mutagenic and genotoxic activity of a CBD isolate (99.4 % CBD content) and CBD-rich Cannabis sativa L extract (63.6 % CBD content) in vitro. Both CBD samples were non-mutagenic, as determined by the AMES test (OECD 471) but exhibited cytotoxicity for HepG2 cells (∼IC50(4 h) 26 µg/ml, ∼IC50(24 h) 6–8 µg/ml, MTT assay). Noncytotoxic concentrations induced upregulation of genes encoding metabolic enzymes involved in CBD metabolism, and CBD oxidative as well as glucuronide metabolites were found in cell culture media, demonstrating the ability of HepG2 cells to metabolize CBD. In this study, the CBD samples were found non-genotoxic. No DNA damage was observed with the comet assay, and no influence on genomic instability was observed with the cytokinesis block micronucleus and the γH2AX and p-H3 assays. Furthermore, no changes in the expression of genes involved in genotoxic stress response were detected in the toxicogenomic analysis, after 4 and 24 h of exposure. Our comprehensive study contributes valuable insights into CBD's safety profile, paving the way for further exploration of CBD's therapeutic applications and potential adverse effects.
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•At non-cytotoxic concentrations CBD samples upregulated genes involved in CBD metabolism (CYP1A1, CYP3A4 and UGT1A3).•CBD oxidative, as well as glucuronide metabolites, were found in cell culture media.•CBD samples exhibited cytotoxicity, with IC50 values of 26 µg/ml, and 6–8 µg/ml after 4 and 24 h of exposure, respectively.•The tested CBD samples were found to be non-mutagenic in the Ames test (OECD 471).•CBD samples were non-genotoxic, with negative results in the comet, CBMN, γH2AX, and p-H3 assays, and toxicogenomics.
Opioids such as morphine are the first choice in acute and chronic pain treatment. However, they lead to addiction. Several studies have searched (i) to find a molecule that can replace morphine use ...or (ii) to reduce its adverse effects. This work aimed to evaluate whether (–)-Borneol (–)-BOR, a bicyclic monoterpene, in doses of 25, 50, and 100 mg/kg (i.p.), has an antiaddictive effect on morphine (5 mg/kg, i.p.) and reduces its withdrawal symptoms precipitated by naloxone (8 mg/kg, i.p.) in Swiss mice. Furthermore, the (–)-BOR genotoxic potential was also investigated by the comet assay. The antiaddictive effect of (–)-BOR was evaluated by the conditioned preference place (CPP). The CPP was induced by morphine administration during the conditioning phase. The effects of (–)-BOR on the rewarding characteristics of morphine were tested in mice with the administration of (–)-BOR, naloxone, or vehicle (NaCl 0.9%), 30 min before morphine. This work also investigated the (–)-BOR effect on morphine withdrawal symptoms precipitated by naloxone. Morphine withdrawal symptoms were induced by administering morphine twice daily for 5 days, precipitated by naloxone administration on the sixth day. The effect of (–)-BOR on reducing morphine withdrawal symptoms was evaluated in mice that received (–)-BOR before daily morphine administration. Finally, the comet assay was performed to assess the DNA damage degree caused by the (–)-BOR (100 mg/kg, i.p.) administration. The comet assay was performed on peripheral blood taken from the tail of each animal. Cyclophosphamide (50 mg/kg, i.p.) was used to induce DNA damage. After starting the protocol, analyses were performed for 4 h (acute effect) and 24 h (repair effect). The (–)-BOR (100 mg/kg, i.p.) significantly attenuated (*** p < 0.001) the acquisition of morphine-induced CPP and reduced only the jumping behavior in the morphine withdrawal model. The best-studied dose was 100 mg/kg, being evaluated, then, in the comet assay. (–)-BOR at 100 mg/kg did not show the genotoxic effect when compared with the cyclophosphamide group (CYCLO, 50 mg/kg, i.p.) after 4 h or 24 h, a period that corresponded to the repair time of DNA fragmentation. The study showed that (–)-BOR attenuated the acquisition of CPP by morphine and made opioid withdrawal milder. In the comet assay, although (–)-BOR caused DNA damage, this damage was significantly less than the damage by CYCLO, at either 4 h or 24 h after the treatments.
•Artemia spp. displays a low sensitivity in several ecotoxicological assessments.•Morphological endpoints are widely employed for detecting acute/chronic toxicity.•New emerging pollutants and trace ...metals are the most tested compounds.•NGS provide additional tools to evaluate the molecular response of Artemia spp.•Genotoxicity is suggested as a novel endpoint in Artemia spp. models.
Artemia spp. represent models species widely used in ecotoxicological studies due to its simple and fast manipulation in laboratory conditions that makes this crustacean well adaptable to several methodological approaches. Although cysts hatching, swimming behavior, reproductive success and mortality are the main endpoints used for the determination of toxicity, the detection of slight alterations induced by certain substances found at low concentrations in the environment may require more sensitive biomarkers. For this reason, the identification of DNA or chromosomal damages has been proposed as an additional and appreciable endpoint for the ecotoxicological assessment of environmental chemicals. Concerning Artemia models, only few studies indicated that the exposure to organic and inorganic compounds (i.e. pesticides, nanoparticles, bacterial products or heavy metals) can reduce the survival and fitness through the onset of DNA breaks or the dysregulation of key genes. In contrast, literature research revealed a lot of works primarily focusing on the mortality and hatching rates of Artemia nauplii and cysts despite the well-known low sensitivity of these species.
The present review reports the current state of knowledge concerning the effects induced by various chemicals, including organic and inorganic compounds, on the common parameters and genotoxicity in both Artemia franciscana and Artemia salina. Advantages and limitations of Artemia spp. models in eco-toxicological investigations together with the most used classes of compounds are briefly discussed. Moreover, a mention is also addressed to scarce availability of literature data focusing on genotoxic effects and the great reliability of molecular approaches observed in this poorly sensitive model organism. Thus, the opportunity to take advantage of genotoxic analyses has also been highlighted, by suggesting this approach as a novel endpoint to be used for the eco-toxicological assessment of several stressors.
Epidemiological studies have demonstrated that metformin (a cornerstone of diabetes treatment) has anticancer activity, but the underlying mechanism remains elusive. We aimed to investigate whether ...metformin elicits anticancer activity via increasing genotoxic stress, a state of increased genome damage that becomes tumor-suppressing if it goes beyond an intolerable threshold. We found that metformin (1–16 mM) suppressed proliferation and colony formation in a panel of cancer cell lines (HeLa, A375, A549 and QGY). Metformin induced a dose-dependent increase of genotoxic stress (including micronucleus, nucleoplasmic bridge and nuclear bud) and the increase of genotoxic stress correlated well with metformin's anticancer potential. Metformin deregulated the expression of BUBR1 and MAD2, two core genes of spindle assembly checkpoint (SAC) that surveillances chromosome segregation. Metformin had weakened antiproliferative effect and a corresponding attenuated genotoxic effect in HeLa cells cultured in high glucose (16 mg/ml). Meanwhile, metformin significantly increased genotoxicity in non-cancer cells (NCM460 and HUVECs). Metformin became non-genotoxic to HUVECs in high-glucose (8 and 16 mg/ml) conditions and reduced the genotoxicity of high glucose. Overall, these results infer a new mechanism of high-dose metformin, whereby low-glucose dependent genotoxic stress derived from SAC dysfunction might mediate some of the anticancer effect of this drug.
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•Metformin elicits short- and long-term effects to inhibit the growth of cancer cells.•Metformin causes significant genotoxic stress in cancer cells.•Metformin de-regulates the expression of core SAC genes.•Metformin is genotoxic to non-cancer cells.•The genotoxic and anti-genotoxic effects of metformin depend on glucose availability.
In vitro genotoxicity testing that employs metabolically active human cells may be better suited for evaluating human in vivo genotoxicity than current bacterial or non-metabolically active mammalian ...cell systems. In the current study, 28 compounds, known to have different genotoxicity and carcinogenicity modes of action (MoAs), were evaluated over a wide range of concentrations for the ability to induce DNA damage in human HepG2 and HepaRG cells. DNA damage dose–responses in both cell lines were quantified using a combination of high-throughput high-content (HTHC) CometChip technology and benchmark dose (BMD) quantitative approaches. Assays of metabolic activity indicated that differentiated HepaRG cells had much higher levels of cytochromes P450 activity than did HepG2 cells. DNA damage was observed for four and two out of five indirect-acting genotoxic carcinogens in HepaRG and HepG2 cells, respectively. Four out of seven direct-acting carcinogens were positive in both cell lines, with two of the three negatives being genotoxic mainly through aneugenicity. The four chemicals positive in both cell lines generated HTHC Comet data in HepaRG and HepG2 cells with comparable BMD values. All the non-genotoxic compounds, including six non-genotoxic carcinogens, were negative in HepaRG cells; five genotoxic non-carcinogens also were negative. Our results indicate that the HTHC CometChip assay detects a greater proportion of genotoxic carcinogens requiring metabolic activation (i.e., indirect carcinogens) when conducted with HepaRG cells than with HepG2 cells. In addition, BMD genotoxicity potency estimate is useful for quantitatively evaluating CometChip assay data in a scientifically rigorous manner.
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