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Toxicogenomics provides insights to toxicity pathways of neonicotinoids to aquatic insect, Chironomus dilutus
2020
Wei, Fenghua | Wang, Dali | Li, Huizhen | Xia, Pu | Ran, Yong | Yau, Ching
Neonicotinoid insecticides have posed a great threat to non-target organisms, yet the mechanisms underlying their toxicity are not well characterized. Major modes of action (MoAs) of imidacloprid were analyzed in an aquatic insect Chironomus dilutus. Lethal and sublethal outcomes were assessed in the midges after 96-h exposure to imidacloprid. Global transcriptomic profiles were determined using de novo RNA-sequencing to more holistically identify toxicity pathways. Transcriptional 10% biological potency values derived from ranked KEGG pathways and GO terms were 0.02 (0.01–0.08) (mean (95% confidence interval) and 0.05 (0.04–0.06) μg L⁻¹, respectively, which were more sensitive than those from phenotypic traits (10% lethal concentration: 0.44 (0.23–0.79) μg L⁻¹; 10% burrowing behavior concentration: 0.30 (0.22–0.43) μg L⁻¹). Major MoAs of imidacloprid in aquatic species were identified as follows: the activation of nicotinic acetylcholine receptors (nAChRs) induced by imidacloprid impaired organisms’ nerve system through calcium ion homeostasis imbalance and mitochondrial dysfunction, which posed oxidative stress and DNA damage and eventually caused death of organisms. The current investigation highlighted that imidacloprid affected C. dilutus at environmentally relevant concentrations, and elucidated toxicity pathways derived from gene alteration to individual outcomes, calling for more attention to toxicity of neonicotinoids to aquatic organisms.
اظهر المزيد [+] اقل [-]Genotoxicity and DNA damage signaling in response to complex mixtures of PAHs in biomass burning particulate matter from cashew nut roasting
2020
Approximately 3 billion people world-wide are exposed to air pollution from biomass burning. Herein, particulate matter (PM) emitted from artisanal cashew nut roasting, an important economic activity worldwide, was investigated. This study focused on: i) chemical characterization of polycyclic aromatic hydrocarbons (PAHs) and oxygenated (oxy-) PAHs; ii) intracellular levels of reactive oxygen species (ROS); iii) genotoxic effects and time- and dose-dependent activation of DNA damage signaling, and iv) differential expression of genes involved in xenobiotic metabolism, inflammation, cell cycle arrest and DNA repair, using A549 lung cells. Among the PAHs, chrysene, benzo[a]pyrene (B[a]P), benzo[b]fluoranthene, and benz[a]anthracene showed the highest concentrations (7.8–10 ng/m³), while benzanthrone and 9,10-anthraquinone were the most abundant oxy-PAHs. Testing of PM extracts was based on B[a]P equivalent doses (B[a]Pₑq). IC₅₀ values for viability were 5.7 and 3.0 nM B[a]Pₑq at 24 h and 48 h, respectively. At these low doses, we observed a time- and dose-dependent increase in intracellular levels of ROS, genotoxicity (DNA strand breaks) and DNA damage signaling (phosphorylation of the protein checkpoint kinase 1 – Chk1). In comparison, effects of B[a]P alone was observed at micromolar range. To our knowledge, no previous study has demonstrated an activation of pChk1, a biomarker used to estimate the carcinogenic potency of PAHs in vitro, in lung cells exposed to cashew nut roasting extracts. Sustained induction of expression of several important stress response mediators of xenobiotic metabolism (CYP1A1, CYP1B1), ROS and pro-inflammatory response (IL-8, TNF-α, IL-2, COX2), and DNA damage response (CDKN1A and DDB2) was also identified. In conclusion, our data show high potency of cashew nut roasting PM to induce cellular stress including genotoxicity, and more potently when compared to B[a]P alone. Our study provides new data that will help elucidate the toxic effects of low-levels of PAH mixtures from air PM generated by cashew nut roasting.
اظهر المزيد [+] اقل [-]Reduced phytotoxicity of nonylphenol on tomato (Solanum lycopersicum L.) plants by earthworm casts
2020
Jiang, Lei | Wang, Bingjie | Liang, Jingqi | Pan, Bo | Yang, Yi | Lin, Yong
Concentrations as high as thousands of milligrams per kilogram (dry weight) of nonylphenol (NP), an endocrine-disrupting chemical of great concern, have been reported in soil. Soil is considered one of the primary pathways for exposure of crop plants to NP. However, there have been few studies on the toxicity of soil NP to crop plants, especially with comprehensive consideration of the application of organic fertiliser which is a common agricultural practice. In this study, tomato plants were grown in soils treated with NP in the presence and/or absence of earthworm casts (EWCs). After four weeks, we tested the physiological and biochemical responses (accumulative levels of hydrogen peroxide (H₂O₂) and superoxide anion radicals (O₂-·), total chlorophyll content, degree of membrane lipid peroxidation, activities of defence-related enzymes, and level of DNA damage) and the changes in plant growth (elongation and biomass). The growth inhibition, reactive oxygen species (H₂O₂ and O₂-·) accumulation, decrease in chlorophyll content, increase in activity of defence-related enzymes (including superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, glutathione S-transferase and glutathione reductase), enhancement of membrane lipid peroxidation, and DNA damage in NP-treated seedlings were clearly reversed by the intervention of EWCs. In particular, the suppressed elongation, biomass, and chlorophyll content in tomato plants exposed to NP alone were significantly restored by EWCs to even greater levels than those of the undisturbed control. In other words, EWCs could efficiently invigorate the photosynthesis of crops via up-regulating the chlorophyll content, thereby overwhelming the NP stress on plant growth. Accordingly, except for reducing the bioavailability of soil NP as reported in our previous study, EWCs could also help crop plants to cope with NP stress by strengthening their stress resistance ability. Our findings are of practical significance for the formulation of strategies to relieve the negative effects of soil NP on crop growth.
اظهر المزيد [+] اقل [-]Application of advanced HepG2 3D cell model for studying genotoxic activity of cyanobacterial toxin cylindrospermopsin
2020
Hercog, Klara | Štampar, Martina | Štern, Alja | Filipič, Metka | Žegura, Bojana
Cylindrospermopsin (CYN) is an emerging cyanotoxin increasingly being found in freshwater cyanobacterial blooms worldwide. Humans and animals are exposed to CYN through the consumption of contaminated water and food as well as occupational and recreational water activities; therefore, it represents a potential health threat. It exhibits genotoxic effects in metabolically active test systems, thus it is considered as pro-genotoxic. In the present study, the advanced 3D cell model developed from human hepatocellular carcinoma (HepG2) cells was used for the evaluation of CYN cyto-/genotoxic activity. Spheroids were formed by forced floating method and were cultured for three days under static conditions prior to exposure to CYN (0.125, 0.25 and 0.5 μg/mL) for 72 h. CYN influence on spheroid growth was measured daily and cell survival was determined by MTS assay and live/dead staining. The influence on cell proliferation, cell cycle alterations and induction of DNA damage (γH2AX) was determined using flow cytometry. Further, the expression of selected genes (qPCR) involved in the metabolism of xenobiotics, proliferation, DNA damage response, apoptosis and oxidative stress was studied. Results revealed that CYN dose-dependently reduced the size of spheroids and affected cell division by arresting HepG2 cells in G1 phase of the cell cycle. No induction of DNA double strand breaks compared to control was determined at applied conditions. The analysis of gene expression revealed that CYN significantly deregulated genes encoding phase I (CYP1A1, CYP1A2, CYP3A4, ALDH3A) and II (NAT1, NAT2, SULT1B1, SULT1C2, UGT1A1, UGT2B7) enzymes as well as genes involved in cell proliferation (PCNA, TOP2α), apoptosis (BBC3) and DNA damage response (GADD45a, CDKN1A, ERCC4). The advanced 3D HepG2 cell model due to its more complex structure and improved cellular interactions provides more physiologically relevant information and more predictive data for human exposure, and can thus contribute to more reliable genotoxicity assessment of chemicals including cyanotoxins.
اظهر المزيد [+] اقل [-]Effects of different mobile phone UMTS signals on DNA, apoptosis and oxidative stress in human lymphocytes
2020
Gulati, Sachin | Kosik, Pavol | Durdik, Matus | Skorvaga, Milan | Jakl, Lukas | Markova, Eva | Belyaev, Igor
Different scientific reports suggested link between exposure to radiofrequency radiation (RF) from mobile communications and induction of reactive oxygen species (ROS) and DNA damage while other studies have not found such a link. However, the available studies are not directly comparable because they were performed at different parameters of exposure, including carrier frequency of RF signal, which was shown to be a critical for appearance of the RF effects. For the first time, we comparatively analyzed genotoxic effects of UMTS signals at different frequency channels used by 3G mobile phones (1923, 1947.47, and 1977 MHz). Genotoxicity was examined in human lymphocytes exposed to RF for 1 h and 3 h using complimentary endpoints such as induction of ROS by imaging flow cytometry, DNA damage by alkaline comet assay, mutations in TP53 gene by RSM assay, preleukemic fusion genes (PFG) by RT-qPCR, and apoptosis by flow cytometry. No effects of RF exposure on ROS, apoptosis, PFG, and mutations in TP53 gene were revealed regardless the UMTS frequency while inhibition of a bulk RNA expression was found. On the other hand, we found relatively small but statistically significant induction of DNA damage in dependence on UMTS frequency channel with maximal effect at 1977.0 MHz. Our data support a notion that each specific signal used in mobile communication should be tested in specially designed experiments to rule out that prolonged exposure to RF from mobile communication would induce genotoxic effects and affect the health of human population.
اظهر المزيد [+] اقل [-]Polycyclic aromatic compounds (PACs) in the Canadian environment: Exposure and effects on wildlife
2020
Wallace, S.J. | de Solla, S.R. | Head, J.A. | Hodson, P.V. | Parrott, J.L. | Thomas, P.J. | Berthiaume, A. | Langlois, V.S.
Polycyclic aromatic compounds (PACs) are ubiquitous in the environment. Wildlife (including fish) are chronically exposed to PACs through air, water, sediment, soil, and/or dietary routes. Exposures are highest near industrial or urban sites, such as aluminum smelters and oil sands mines, or near natural sources such as forest fires. This review assesses the exposure and toxicity of PACs to wildlife, with a focus on the Canadian environment. Most published field studies measured PAC concentrations in tissues of invertebrates, fish, and birds, with fewer studies of amphibians and mammals. In general, PAC concentrations measured in Canadian wildlife tissues were under the benzo[a]pyrene (BaP) guideline for human consumption. Health effects of PAC exposure include embryotoxicity, deformities, cardiotoxicity, DNA damage, changes to DNA methylation, oxidative stress, endocrine disruption, and impaired reproduction. Much of the toxicity of PACs can be attributed to their bioavailability, and the extent to which certain PACs are transformed into more toxic metabolites by cytochrome P450 enzymes. As most mechanistic studies are limited to individual polycyclic aromatic hydrocarbons (PAHs), particularly BaP, research on other PACs and PAC-containing complex mixtures is required to understand the environmental significance of PAC exposure and toxicity. Additional work on responses to PACs in amphibians, reptiles, and semi-aquatic mammals, and development of molecular markers for early detection of biological responses to PACs would provide a stronger biological and ecological justification for regulating PAC emissions to protect Canadian wildlife.
اظهر المزيد [+] اقل [-]Graphene oxide exposure suppresses nitrate uptake by roots of wheat seedlings
2020
Weng, Yineng | You, Yue | Lu, Qi | Zhong, Ao | Liu, Siyi | Liu, Huijun | Du, Shaoting
Despite the large number of studies reporting the phytotoxicity of graphene-based materials, the effects of these materials on nutrient uptake in plants remain unclear. The present study showed that nitrate concentrations were significantly decreased in the roots of wheat plants treated with graphene oxide (GO) at 200–800 mg L⁻¹. Non-invasive microelectrode measurement demonstrated that GO could significantly inhibit the net NO₃⁻ influx in the meristematic, elongation, and mature zones of wheat roots. Further analysis indicated that GO could be trapped in the root vacuoles, and that the maximal root length and the number of lateral roots were significantly reduced. Additionally, root tip whitening, creases, oxidative stress, and weakened respiration were observed. These observations indicate that GO is highly unfavorable for vigorous root growth and inhibits increase in root uptake area. At the molecular level, GO exposure caused DNA damage and inhibited the expression of most nitrate transporters (NRTs) in wheat roots, with the most significantly downregulated genes being NRT1.3, NRT1.5, NRT2.1, NRT2.3, and NRT2.4. We concluded that GO exposure decreased the root uptake area and root activity, and decreased the expression of NRTs, which may have consequently suppressed the NO₃⁻ uptake rate, leading to adverse nitrate accumulation in stressed plants.
اظهر المزيد [+] اقل [-]Adverse effects of in vitro GenX exposure on rat thyroid cell viability, DNA integrity and thyroid-related genes expression
2020
Coperchini, Francesca | Croce, Laura | Denegri, Marco | Pignatti, Patrizia | Agozzino, Manuela | Netti, Giuseppe Stefano | Imbriani, Marcello | Rotondi, Mario | Chiovato, Luca
The hexafluoropropylene-oxide-dimer-acid (GenX) is a short-chain perfluoroalkyl substance that was recently introduced following the phase out of PFOA, as an alternative for the process of polymerization. GenX was detected at high concentrations in rivers, drinking water and in sera of exposed workers and recent findings suggested its potential dangerousness for human health.Aim of the study was to assess the consequences of GenX exposure on in vitro thyroid cells with particular attention to the effects on cell-viability, proliferation, DNA-damage and in the thyroid-related genes expression.FRTL-5 rat-thyroid cell line were incubated with increasing concentrations of GenX for 24 h, 48 h and 72 h to assess cell viability by WST-1. DNA-damage was assessed by comet assay and further confirmed by micronucleus assay. The proliferation of survived cells was measured by staining with crystal violet and evaluation of its optical density after incubation with SDS. Changes in TTF-1, Pax8, Tg, TSH-R, NIS and TPO genes expression were evaluated by RT-PCR.GenX exposure reduced FRTL-5 viability in a time and dose-dependent manner (24 h: ANOVA F = 22.286; p < 0.001; 48 h: F = 43.253, p < 0.001; 72 h: F = 49.708, p < 0.001). Moreover, GenX exerted a genotoxic effect, as assessed by comet assay (significant increase in tail-length, olive-tail-moment and percentage of tail-DNA) and micronucleus assay, both at cytotoxic and non-cytotoxic concentrations. Exposure to GenX at concentrations non-cytotoxic exerted a significant lowering of the expression of the regulatory gene TTF-1 (p < 0.05 versus untreated) and higher expression of Pax-8 (p < 0.05 versus untreated) and a down-regulation of NIS (p < 0.05 versus untreated). In addition, cells survived to GenX exposure showed a reduced re-proliferation ability (24 h: ANOVA F = 11,941; p < 0,001; 48 h: F = 93.11; p < 0.001; 72 h F = 21.65; p < 0.001).The exposure to GenX produces several toxic effects on thyroid cells in vitro. GenX is able to promote DNA-damage and to affect the expression of thyroid transcription-factor genes.
اظهر المزيد [+] اقل [-]Visible-light reduced silver nanoparticles’ toxicity in Allium cepa test system
2020
Souza, Irisdoris R. | Silva, Lucas R. | Fernandes, Letícia S.P. | Salgado, Lilian D. | Silva de Assis, Helena C. | Firak, Daniele S. | Bach, Larissa | Santos-Filho, Ronaldo | Voigt, Carmen L. | Barros, Ariana C. | Peralta-Zamora, Patricio | Mattoso, Ney | Franco, Celia Regina C. | Soares Medeiros, Lia C. | Marcon, Bruna H. | Cestari, Marta M. | Sant’Anna-Santos, Bruno F. | Leme, Daniela M.
Silver nanoparticles (AgNPs) are widely used in consumer products due to their antibacterial property; however, their potential toxicity and release into the environment raises concern. Based on the limited understanding of AgNPs aggregation behavior, this study aimed to investigate the toxicity of uncoated (uc-AgNP) and coated with polyvinylpyrrolidone (PVP-AgNP), at low concentrations (0.5–100 ng/mL), under dark and visible-light exposure, using a plant test system. We exposed Allium cepa seeds to both types of AgNPs for 4–5 days to evaluate several toxicity endpoints. AgNPs did not cause acute toxicity (i.e., inhibition of seed germination and root development), but caused genotoxicity and biochemical alterations in oxidative stress parameters (lipid peroxidation) and activities of antioxidant enzymes (superoxide dismutase and catalase) in light and dark conditions. However, the light exposure decreased the rate of chromosomal aberration and micronuclei up to 5.60x in uc-AgNP and 2.01x in PVP-AgNP, and 2.69x in uc-AgNP and 3.70x in PVP-AgNP, respectively. Thus, light exposure reduced the overall genotoxicity of these AgNPs. In addition, mitotic index alterations and morphoanatomical changes in meristematic cells were observed only in the dark condition at the highest concentrations, demonstrating that light also reduces AgNPs cytotoxicity. The light-dependent aggregation of AgNPs may have reduced toxicity by reducing the uptake of these NPs by the cells. Our findings demonstrate that AgNPs can be genotoxic, cytotoxic and induce morphoanatomical and biochemical changes in A. cepa roots even at low concentrations, and that visible-light alters their aggregation state, and decreases their toxicity. We suggest that visible light can be an alternative treatment to remediate AgNP residues, minimizing their toxicity and environmental risks.
اظهر المزيد [+] اقل [-]In vitro evaluation of the cytotoxicity, mutagenicity and DNA damage induced by particle matter and gaseous emissions from a medium-duty diesel vehicle under real driving conditions using palm oil biodiesel blends
2020
Botero, Maria L. | Mendoza, Carolina | Arias, Silvana | Hincapié, Oscar D. | Agudelo, John R. | Ortiz, Isabel C.
The influence of palm oil biodiesel content on the cytotoxicity, mutagenicity and genotoxicity of particle- and gas-phase diesel vehicle emissions was investigated. The emissions were collected on-board of a EURO IV diesel truck, fuelled with mixtures of 10% (B10), 20% (B20) and 100% (B100) of palm oil biodiesel, under real driving conditions. Organic extracts of the particulate matter (PM) and gases were characterised for 17 PAH (including EPA priority) and used for the biological assay. Increasing biodiesel content in the fuel mixture results in a decrease in the PM and PAH emission factors, both in the particulate and gas-phase. The majority of the PAH are present in the gas-phase. The mutagenic potencies, in TA98 bacteria, are higher for B20 in both phases, whereas the mutagenicity emission factor, that takes into account the lower emission of PM and PAH, is not significantly different between the fuels. Higher direct mutagenicity (TA98 + S9) is observed in all the tested fuels, indicating the action of carcinogenic compounds other than non-substituted PAH. The gas-phase extracts present higher cytotoxicity and genotoxicity in lung epithelial cell A549, which may be related to the higher PAH content in the gas-phase. The increase in biodiesel content have a different impact on cytotoxicity, being larger in the gas-phase and lower in the particle-phase. This indicates that pulmonary toxicity may be higher for the gaseous emissions, due to the role of different toxic compounds compared to the PM. The adverse biological effects when biodiesel content increases are not consequent with the reduction of the PAH characterised, indicating that other toxic compounds are more relevant. Further investigations to identify these compounds are required in order to update and focus the efforts regarding emission targets and controls.
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