ABSTRACT
Heavy metals are now persistently present in living things' environments, in addition to their potential toxicity. Therefore, the aim of this study was to utilize D. melanogaster to determine the biological effects induced by different heavy metals including cadmium chloride (CdCl2), copper (II) sulfate pentahydrate (CuSO 4.5â¯H2O), and silver nitrate (AgNO3). In vivo experiments were conducted utilizing three low and environmentally relevant concentrations from 0.01 to 0.5â¯mM under single and combined exposure scenarios on D. melanogaster larvae. The endpoints measured included viability, reactive oxygen species (ROS) generation and genotoxic effects using Comet assay and the wing-spot test. Results indicated that tested heavy metals were not toxic in the egg-to adult viability. However, combined exposure (CdCl2+AgNO3 and CdCl2+AgNO3+CuSO 4.5â¯H2O) resulted in significant genotoxic and unfavorable consequences, as well as antagonistic and/or synergistic effects on oxidative damage and genetic damage.
Subject(s)
Environmental Pollutants , Metals, Heavy , Animals , Cadmium , Copper/toxicity , Drosophila melanogaster/genetics , Environmental Pollutants/toxicity , Metals, Heavy/toxicity , DNA DamageABSTRACT
Agriculture commonly utilizes crop protection products to tackle infestations from fungi, parasites, insects, and weeds. Validamycin A, an inhibitor of trehalase, possesses antibiotic and antifungal attributes. Epidemiological evidence has led to concerns regarding a potential link between pesticide usage and neurodegenerative diseases. The fruit fly, Drosophila melanogaster, has been recognized as a reliable model for genetic research due to its significant genetic similarities with mammals. Here, we propose to use D. melanogaster as an effective in vivo model system to investigate the genotoxic risks associated with exposure to validamycin A. In this study, we performed a neurotoxic evaluation of validamycin A in D. melanogaster larvae. Several endpoints were evaluated, including toxicity, intracellular oxidative stress (reactive oxygen species), intestinal damage, larval behavior (crawling behavior, light/dark sensitivity assay, and temperature sensitivity assay), locomotor (climbing) behavior, and neurogenotoxic effects (impaired DNA via Comet assay, enhanced by Endo III and formamidopyrimidine DNA glycosylase [FPG]). The results showed that exposure to validamycin A, especially at higher doses (1 and 2.5 mM), induced DNA impairment in neuroblasts as observed by Comet assay. Both larvae and adults exhibited behavioral changes and produced reactive oxygen species. Most importantly, this research represents a pioneering effort to report neurogenotoxicity data specifically in Drosophila larval neuroblasts, thus underscoring the importance of this species as a testing model in exploring the biological impacts of validamycin A. The in vivo findings from the experiments are a valuable and novel addition to the existing validamycin A neurogenotoxicity database.
Subject(s)
Brain , Drosophila melanogaster , Inositol/analogs & derivatives , Animals , Drosophila melanogaster/genetics , Reactive Oxygen Species , Larva , DNA , MammalsABSTRACT
Autophagy is the process through which a body breaks down and recycles its own cellular components, primarily inside lysosomes. It is a cellular response to starvation and stress, which plays decisive roles in various biological processes such as senescence, apoptosis, carcinoma, and immune response. Autophagy, which was first discovered as a survival mechanism during starvation in yeast, is now known to serve a wide range of functions in more advanced organisms. It plays a vital role in how cells respond to stress, starvation, and infection. While research on yeast has led to the identification of many key components of the autophagy process, more research into autophagy in more complex systems is still warranted. This review article focuses on the use of the fruit fly Drosophila melanogaster as a robust testing model in further research on autophagy. Drosophila provides an ideal environment for exploring autophagy in a living organism during its development. Additionally, Drosophila is a well-suited compact tool for genetic analysis in that it serves as an intermediate between yeast and mammals because evolution conserved the molecular machinery required for autophagy in this species. Experimental tractability of host-pathogen interactions in Drosophila also affords great convenience in modeling human diseases on analogous structures and tissues.
ABSTRACT
Propionic acid is a short-chain fatty acid that is the main fermentation product of the enteric microbiome. It is found naturally and added to foods as a preservative and evaluated by health authorities as safe for use in foods. However, propionic acid has been reported in the literature to be associated with both health and disease. The purpose of this work is to better understand how propionic acid affects Drosophila melanogaster by examining some of the effects of this compound on the D. melanogaster hemocytes. D. melanogaster was chosen as a suitable in vivo model to detect potential risks of propionic acid (at five concentrations ranging from 0.1 to 10 mM) used as a food preservative. Toxicity, cellular immune response, intracellular oxidative stress (reactive oxygen species, ROS), gut damage, and DNA damage (via Comet assay) were the end-points evaluated. Significant genotoxic effects were detected in selected cell targets in a concentration dependent manner, especially at two highest concentrations (5 and 10 mM) of propionic acid. This study is the first study reporting genotoxicity data in the hemocytes of Drosophila larvae, emphasizing the importance of D. melanogaster as a model organism in investigating the different biological effects caused by the ingested food preservative product.
Subject(s)
Drosophila melanogaster , Food Preservatives , Animals , Comet Assay , DNA Damage , Drosophila melanogaster/drug effects , Drosophila melanogaster/genetics , Food Preservatives/toxicity , Immunity, Cellular/drug effects , Oxidative Stress/drug effectsABSTRACT
Plastic waste in different environments has been constantly transforming into microplastic/nanoplastic (MNPLs). As they may coexist with other contaminants, they may behave as vectors that transport various toxic trace elements, including metals. Because the impact of exposure to such matter on health still remains elusive, the abundant presence of MNPLs has lately become a pressing environmental issue. Researchers have been utilizing Drosophila melanogaster as a dynamic in vivo model in genetic research for some time. The fly has also recently gained wider recognition in toxicology and nanogenotoxicity studies. The use of nanoparticles in numerous medical and consumer products raises serious concern, since many in vitro studies have shown their toxic potential. However, there is rather limited in vivo research into nanomaterial genotoxicity using mice or other mammalians owing to high costs and ethical concerns. In this context, Drosophila, thanks to its genetic tractability, short life span, with its entire life cycle lasting about 10 days, and distinct developmental stages, renders this organism an excellent model in testing toxic effects mediated by MNPLs. This review therefore aims to encourage research entities to employ Drosophila as a model in their nanogenotoxicity experiments focusing on impact of MNPLs at the molecular level.
Subject(s)
Metals, Heavy , Nanostructures , Water Pollutants, Chemical , Animals , Mice , Microplastics , Drosophila melanogaster/genetics , Plastics/toxicity , Metals, Heavy/toxicity , Nanostructures/toxicity , Mammals , Water Pollutants, Chemical/toxicityABSTRACT
Humans and animals may be exposed on a continuous daily basis to a mixture of environmental contaminants that may act on several organ systems through differing mechanisms [...].
Subject(s)
Ecotoxicology , HumansABSTRACT
Living organisms are now constantly exposed to microplastics and nanoplastics (MNPLs), and besides their toxic potential, they can also act as carriers of various hazardous elements such as heavy metals. Therefore, this study explored possible interactions between polystyrene microplastics (PSMPLs) and two metal pollutants: cadmium chloride (CdCl2) and silver nitrate (AgNO3). To better understand the extent of biological effects caused by different sizes of PSMPLs, we conducted in vivo experiments with five doses (from 0.01 to 10 mM) that contained polystyrene particles measuring 4, 10, and 20 µm in size on Drosophila larvae. Additional experiments were performed by exposing larvae to two individual metals, CdCl2 (0.5 mM) and AgNO3 (0.5 mM), as well as combined exposure to PSMPLs (0.01 and 10 mM) and these metals, in an attempt to gain new insight into health risks of such co-exposure. Using transmission electron microscopy imaging, we managed to visualize the biodistribution of ingested PSMPLs throughout the fly's body, observing the interactions of such plastics with Drosophila intestinal lumen, cellular uptake by gut enterocytes, the passage of plastic particles through the intestinal barrier to leak into the hemolymph, and cellular uptake by hemocytes. Observations detected size and shape changes in the ingested PSMPLs. Egg-to-adult viability screening revealed no significant toxicity upon exposure to individual doses of tested materials; however, the combined exposure to plastic and metal particles induced aggravated genotoxic effects, including intestinal damage, genetic damage, and intracellular oxidative stress (ROS generation), with smaller sized plastic particles + metals (cadmium and silver) causing greater damage.
ABSTRACT
New insights into the interactions between nanopesticides and edible plants are required in order to elucidate their impacts on human health and agriculture. Nanopesticides include formulations consisting of organic/inorganic nanoparticles. Drosophila melanogaster has become a powerful model in genetic research thanks to its genetic similarity to mammals. This project mainly aimed to generate new evidence for the toxic/genotoxic properties of different nanopesticides (a nanoemulsion (permethrin nanopesticides, 20 ± 5 nm), an inorganic nanoparticle as an active ingredient (copper(II) hydroxide [Cu(OH)2] nanopesticides, 15 ± 6 nm), a polymer-based nanopesticide (acephate nanopesticides, 55 ± 25 nm), and an inorganic nanoparticle associated with an organic active ingredient (validamycin nanopesticides, 1177 ± 220 nm)) and their microparticulate forms (i.e., permethrin, copper(II) sulfate pentahydrate (CuSO4·5H2O), acephate, and validamycin) widely used against agricultural pests, while also showing the merits of using Drosophila-a non-target in vivo eukaryotic model organism-in nanogenotoxicology studies. Significant biological effects were noted at the highest doses of permethrin (0.06 and 0.1 mM), permethrin nanopesticides (1 and 2.5 mM), CuSO4·5H2O (1 and 5 mM), acephate and acephate nanopesticides (1 and 5 mM, respectively), and validamycin and validamycin nanopesticides (1 and 2.5 mM, respectively). The results demonstrating the toxic/genotoxic potential of these nanopesticides through their impact on cellular internalization and gene expression represent significant contributions to future nanogenotoxicology studies.
Subject(s)
Copper , Permethrin , Animals , Copper/toxicity , Drosophila , Drosophila melanogaster , Humans , Hydroxides , Inositol/analogs & derivatives , Mammals , Organothiophosphorus Compounds , Permethrin/toxicity , PhosphoramidesABSTRACT
Boron trioxide nanoparticles (B2 O3 NPs) have recently been widely used in a range of applications including electronic device technologies, acousto-optic apparatus fields, and as nanopowder for the production of special glasses. We propose Drosophila melanogaster as a useful in vivo model system to study the genotoxic risks associated with NP exposure. In this study, we have conducted a genotoxic evaluation of B2 O3 NPs (size average 55.52 ± 1.41 nm) and its ionic form in D. melanogaster. B2 O3 NPs were supplied to third instar larvae at concentrations ranging from 0.1-10 mM. Toxicity, intracellular oxidative stress (reactive oxygen species, ROS), phenotypic alterations, genotoxic effect (via the wing somatic mutation and recombination test, SMART), and DNA damage (via Comet assay) were the end-points evaluated. B2 O3 NPs did not cause any mutagenic/recombinogenic effects in all tested non-toxic concentrations in Drosophila SMART. Negative data were also obtained with the ionic form. Exposure to B2 O3 NPs and its ionic form (at two highest concentrations, 2.5 and 5 mM) was found to induce DNA damage in Comet assay. Additionally, ROS induction in hemocytes and phenotypic alterations were determined in the mouths and legs of Drosophila. This study is the first study reporting genotoxicity data in the somatic cells of Drosophila larvae, emphasizing the importance of D. melanogaster as a model organism in investigating the different biological effects in a concentration-dependent manner caused by B2 O3 NPs and its ionic form. The obtained in vivo results contribute to improvement the genotoxicity database on the B2 O3 NPs.
Subject(s)
Drosophila melanogaster , Nanoparticles , Animals , Boron , DNA Damage , Drosophila/genetics , Drosophila melanogaster/genetics , Ions , Larva/genetics , Mutagenicity Tests , Mutagens/toxicity , Nanoparticles/toxicity , Oxidative Stress , Reactive Oxygen SpeciesABSTRACT
Nanotechnology is often praised as the future technology that will revolutionize the world as we know it, because nanomaterials (NMs) offer numerous practical applications for a wide range of fields such as medicine, cosmetics, food preservation, paintings, and industry. Produced by nanotechnology, NMs are in the front line of this innovative applied science, while nanoparticles (NPs) refer to materials existing in the natural world and measuring 1-100 nanometers in at least one dimension. The recent surge in the number of endeavors to utilize NMs makes it imperative to identify hazards and risk factors involved as we have yet to know harmful effects of this uncharted territory on the environment and public health. While researchers generally choose to carry out in vitro experiments in an effort to assess toxicity of NMs, in vivo approaches seem to yield better evidence that is more relevant to risk assessment. In that context, Drosophila melanogaster stands out as the most dynamic model organism for biological experiments, since 75% of the genes responsible for human diseases are known to have homologs in D. melanogaster, which facilitates research into various pathologies. This book chapter aims to present the full picture of studies on separate NMs that employed in vivo approaches (toxicity, genotoxicity, internalization, cell uptake, tissue distribution, etc.) using D. melanogaster, attempting to offer an in-depth analysis of risks involved in exposure to NMs, as well as many advantages of other animal models used by nanogenotoxicology studies.
Subject(s)
Nanoparticles , Nanostructures , Animals , Drosophila , Drosophila melanogaster/genetics , Nanoparticles/toxicity , Nanostructures/toxicity , NanotechnologyABSTRACT
The use of graphene and multi-walled carbon nanotubes (MWCNTs) has now become rather common in medical applications as well as several other areas thanks to their useful physicochemical properties. While in vitro testing offers some potential, in vivo research into toxic effects of graphene and MWCNTs could yield much more reliable data. Drosophila melanogaster has recently gained significant popularity as a dynamic eukaryotic model in examining toxicity, genotoxicity, and biological effects of exposure to nanomaterials, including oxidative stress, cellular immune response against two strains (NSRef and G486) of parasitoid wasp (Leptopilina boulardi), phenotypic variations, and locomotor behavior risks. D. melanogaster was used as a model organism in our study to identify the potential risks of exposure to graphene (thickness: 2-18 nm) and MWCNTs in different properties (as pure [OD: 10-20 nm short], modified by amide [NH2 ] [OD: 7-13 nm length: 55 µm], and modified by carboxyl [COOH] [OD: 30-50 nm and length: 0.5-2 µm]) at concentrations ranging from 0.1 to 250 µg/ml. Significant effects were observed at two high doses (100 and 250 µg/ml) of graphene or MWCNTs. This is the first study to report findings of cellular immune response against hematopoiesis and parasitoids, nanogenotoxicity, phenotypic variations, and locomotor behavior in D. melanogaster.
Subject(s)
DNA Damage , Drosophila melanogaster/drug effects , Graphite/toxicity , Host-Parasite Interactions/drug effects , Nanotubes, Carbon/toxicity , Oxidative Stress/drug effects , Animals , Drosophila melanogaster/immunology , Drosophila melanogaster/parasitology , Drosophila melanogaster/physiology , Immunity, Cellular/drug effects , Locomotion/drug effects , PhenotypeABSTRACT
The world urgently needs effective antiviral approaches against emerging viruses, as shown by the coronavirus disease 2019 (COVID-19) pandemic, which has become an exponentially growing health crisis. Scientists from diverse backgrounds have directed their efforts towards identifying key features of SARS-CoV-2 and clinical manifestations of COVID-19 infection. Reports of more transmissible variants of SARS-CoV-2 also raise concerns over the possibility of an explosive trajectory of the pandemic, so scientific attention should focus on developing new weapons to help win the fight against coronaviruses that may undergo further mutations in the future. Drosophila melanogaster offers a powerful and potential in vivo model that can significantly increase the efficiency of drug screening for viral and bacterial infections. Thanks to its genes with functional human homologs, Drosophila could play a significant role in such gene-editing studies geared towards designing vaccines and antiviral drugs for COVID-19. It can also help rectify current drawbacks of CRISPR-based therapeutics like off-target effects and delivery issues, representing another momentous step forward in healthcare. Here I present an overview of recent literature and the current state of knowledge, explaining how it can open up new avenues for Drosophila in our battle against infectious diseases.
ABSTRACT
The field of nanotechnology has allowed for increasing nanoparticle (NP) exposure to the male reproductive system. Certain NPs have been reported to have adverse consequences on male germ and somatic cells. Germ cells are the bridge between generations and are responsible for the transmission of genetic and epigenetic information to future generations. A number of NPs have negative impacts on male germ and somatic cells which could ultimately affect fertility or the ability to produce healthy offspring. These impacts are related to NP composition, modification, concentration, agglomeration, and route of administration. NPs can induce severe toxic effects on the male reproduction system after passing through the blood-testis barrier and ultimately damaging the spermatozoa. Therefore, understanding the impacts of NPs on reproduction is necessary. This review will provide a comprehensive overview on the current state of knowledge derived from the previous in vivo and in vitro research on effects of NPs on the male reproductive system at the genetic, cellular, and molecular levels.
Subject(s)
Nanoparticles , Genitalia, Male , Humans , Male , Nanoparticles/toxicity , Nanotechnology , ReproductionABSTRACT
The abundant presence and extensive use of polystyrene microplastics (PSMPs) has recently become a serious environmental concern, as impact of exposure to these substances on human health remains unknown. While in vitro studies yield data on adverse effect of PSMPs, in vivo approaches are more relevant for risk assessment. Drosophila melanogaster is one of the most genetically and experimentally accessible model organisms used in biology as an in vivo model. D. melanogaster was selected as a representative in vivo model organism to examine the genotoxic potential of PSMPs at 5 concentrations of three different sizes namely 4, 10, or 20 µm. In particular, the wing somatic mutation and recombination test (SMART), a scalable, time-efficient in vivo assay developed to study genotoxicity of various compounds in a rapid manner at low costs was used. The third-instar Drosophila larvae were exposed to PSMPs through food at 5 concentrations ranging from 0.01-10 mM. Viability (lethality), larval length, morphological deformations, locomotor activity (climbing behavior), and genotoxic effects were the end-points measured. Exposure to PSMPs at 4, 10, or 20 µm produced significant morphological defects, impaired climbing behavior, and genotoxicity as evidenced by the SMART test demonstrating induction of somatic recombination. Significant increases were observed in the frequency of total spots, suggesting that PSMPs might induce genotoxic activity predominantly via initiation of somatic DNA recombination in a concentration-dependent manner.
Subject(s)
DNA Damage , Drosophila melanogaster/drug effects , Microplastics/toxicity , Nanoparticles/toxicity , Polystyrenes/toxicity , Animals , Dose-Response Relationship, Drug , Drosophila melanogaster/growth & development , Larva/drug effects , Larva/growth & development , Models, AnimalABSTRACT
Nanomaterials (NMs) generally display fascinating physical and chemical properties that are not always present in bulk materials; therefore, any modification to their size, shape, or coating tends to cause significant changes in their chemical/physical and biological characteristics. The dramatic increase in efforts to use NMs renders the risk assessment of their toxicity highly crucial due to the possible health perils of this relatively uncharted territory. The different sizes and shapes of the nanoparticles are known to have an impact on organisms and an important place in clinical applications. The shape of nanoparticles, namely, whether they are rods, wires, or spheres, is a particularly critical parameter to affect cell uptake and site-specific drug delivery, representing a significant factor in determining the potency and magnitude of the effect. This review, therefore, intends to offer a picture of research into the toxicity of different shapes (nanorods, nanowires, and nanospheres) of NMs to in vitro and in vivo models, presenting an in-depth analysis of health risks associated with exposure to such nanostructures and benefits achieved by using certain model organisms in genotoxicity testing. Nanotoxicity experiments use various models and tests, such as cell cultures, cores, shells, and coating materials. This review article also attempts to raise awareness about practical applications of NMs in different shapes in biology, to evaluate their potential genotoxicity, and to suggest approaches to explain underlying mechanisms of their toxicity and genotoxicity depending on nanoparticle shape.
Subject(s)
Chromosome Aberrations/chemically induced , Drug Delivery Systems/adverse effects , Metal Nanoparticles/chemistry , Metal Nanoparticles/toxicity , Animals , Humans , Molecular Conformation , Mutagenicity TestsABSTRACT
One of the fastest-moving fields in today's world of applied science, nanotechnology allows the control and design of matter on an extremely small scale, so it has now become an integral part of various industries and scientific areas, such as agriculture, food sector, healthcare and engineering. Understanding the interactions between nanopesticides and edible plants, as well as non-target animals, is crucial in assessing the potential impact of nanotechnology products on the environment, agriculture and human health. The dramatic increase in efforts to use nanopesticides renders the risk assessment of their toxicity and genotoxicity highly crucial due to the potential adverse impact of this relatively uncharted territory. Such widespread use naturally increases our exposure to nanopesticides, raising concerns over their possible adverse effects on humans and non-target organisms, which might include severe impairment of both male and female reproductive capacity. We therefore need better insight into such effects to derive conclusive evidence on the safety or toxicity/genotoxicity of nanopesticides, and Drosophila melanogaster (fruit fly) can prove an ideal model organism for the risk assessment and toxicological classification of nanopesticides, as it bears striking similarities to various systems in human body. This editorial review attempts to summarize our current knowledge derived from previous in vivo studies to examine the impact of several nanomaterials on various species of mammals and non-target model organisms at the genetic, cellular, and molecular levels, attracting attention to the possible mechanisms and potential toxic/genotoxic effects of nanopesticides widely used in agriculture on D. melanogaster as a non-target organism.
Subject(s)
Animal Use Alternatives , Drosophila melanogaster/drug effects , Nanostructures/toxicity , Pesticides/toxicity , Animals , Drosophila melanogaster/genetics , Humans , Nanostructures/chemistry , Nanotechnology , Pesticides/chemistry , Toxicity TestsABSTRACT
The biological impact of nanomaterials (NMs) is determined by several factors such as size and shape, which need to be taken into consideration in any type of analysis. While investigators often prefer to conduct in vitro studies for detection of any possible adverse effects of NMs, in vivo approaches yield more relevant data for risk assessment. For this reason, Drosophila melanogaster was selected as a suitable in vivo model to characterize the potential risks associated with exposure nanorods (NRs), nanospheres (NSs), nanowires (NWs) forms of titanium dioxide (TiO2), and their microparticulated (or bulk) form, as TiO2. Third instar larvae (72 hr old larvae) were fed with TiO2 (NRs, NSs, or NWs) and TiO2 at concentrations ranging from 0.01 to 10 mM. Viability (toxicity), internalization (cellular uptake), intracellular reactive oxygen species (ROS) production, and genotoxicity (Comet assay) were the end-points evaluated in hemocyte D. melanogaster larvae. Significant intracellular oxidative stress and genotoxicity were noted at the highest exposure concentration (10 mM) of TiO2 (NRs, NSs, or NWs), as determined by the Comet assay and ROS analysis, respectively. A concentration-effect relationship was observed in hemocytes exposed to the NMs. Data demonstrated that selected forms of TiO2.-induced genotoxicity in D. melanogaster larvae hemocytes indicating this organism is susceptible for use as a model to examine in vivo NMs-mediated effects.
Subject(s)
DNA Damage , Nanostructures/toxicity , Oxidative Stress/drug effects , Titanium/toxicity , Animals , Biological Transport , Drosophila melanogaster , Hemocytes/drug effects , Hemocytes/metabolism , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Larva/drug effects , Larva/metabolism , Nanospheres/chemistry , Nanospheres/toxicity , Nanostructures/chemistry , Nanotubes/chemistry , Nanotubes/toxicity , Nanowires/chemistry , Nanowires/toxicity , Reactive Oxygen Species/metabolism , Titanium/chemistry , Titanium/metabolismABSTRACT
Cadmium oxide nanoparticles (CdO NPs) are among some of the most studied and industrially used metal oxide NPs. They have been widely used for industrial application, such as paint pigments and electronic devices, and medical therapeutics. With increasing use of CdO NPs and concerns for their potential adverse effects on the environment and public health, evaluation of the cytotoxicity and genotoxicity of CdO NPs becomes very important. To date, there is a limited understanding of the potential hazard brought by CdO NPs and a lack of information and research, particularly on the genotoxicity assessment of these NPs. In this study, 10 nm CdO core-PEG stabilized NPs were synthesized, characterized and used for evaluation of CdO NPs' cytotoxicity and genotoxicity. Release of cadmium ions (Cd+2) from the CdO NPs in cell culture medium, cellular uptake of the NPs, and the endotoxin content of the particles were measured prior to the toxicity assays. Cytotoxicity was evaluated using the MTS assay, ATP content detection assay, and LDH assay. Genotoxicity was assessed using the Ames test, Comet assay, micronucleus assay, and mouse lymphoma assay. The cytotoxicity of cadmium chloride (CdCl2) was also evaluated along with that of the CdO NPs. The results showed that endotoxin levels within the CdO NPs were below the limit of detection. CdO NPs induced concentration-dependent cytotoxicity in TK6 and HepG2 cells with the MTS, ATP and LDH assays. Although the genotoxicity of CdO NPs was negative in the Ames test, positive results were obtained with the micronucleus, Comet, and mouse lymphoma assays. The negative response of CdO NPs with the Ames test may be the result of unsuitability of the assay for measuring NPs, while the positive responses from other genotoxicity assays suggest that CdO NPs can induce chromosomal damage, single or double strand breaks in DNA, and mutations. The toxicity of the CdO NPs results from the NPs themselves and not from the released Cd+2, because the ions released from the NPs were minimal. These results demonstrate that CdO NPs are cytotoxic and genotoxic and provide new insights into risk assessment of CdO NPs for human exposure and environmental protection.
Subject(s)
Cadmium Compounds/toxicity , Metal Nanoparticles/toxicity , Mutagenicity Tests , Mutagens/toxicity , Oxides/toxicity , Animals , Cadmium Compounds/pharmacology , Cell Line , Cell Survival/drug effects , Comet Assay , DNA Damage/drug effects , Humans , Metal Nanoparticles/chemistry , Mice , Mutagens/pharmacology , Oxides/pharmacologyABSTRACT
Carbon-based nanomaterials are being increasingly used, demanding strong information to support their safety in terms of human health. As ingestion is one of the most important exposure routes in humans, we have determined their potential risk by using an in vitro model simulating the human intestinal barrier and evaluated the effects of both graphene oxide (GO) and graphene nanoplatelets (GNPs). A coculture of differentiated Caco-2/HT29 cells presenting inherent intestinal epithelium characteristics (i.e. mucus secretion, brush border, tight junctions, etc.) were treated with GO or GNPs for 24 h. Different endpoints such as viability, membrane integrity, NPs localization, cytokines secretion, and genotoxic damage were evaluated to have a wide view of their potentially harmful effects. No cytotoxic effects were observed in the cells that constitute the barrier model. In the same way, no adverse effects were detected neither in the integrity of the barrier (TEER) nor in its permeability (LY). Nevertheless, a different bio-adhesion and biodistribution behavior was observed for GO and GNPs by confocal microscopy analysis, with a more relevant uptake of GNPs. No oxidative damage induction was detected, either by the DCFH-DA assay or the FPG enzyme in the comet assay. Conversely, both GO and GNPs were able to induce DNA breaks, as observed in the comet assay. Finally, low levels of anti-inflammatory cytokines were detected, suggesting a weak anti-inflammatory response. Our results show the moderate/severe risk posed by GO/GNPs exposures, given the observed genotoxic effects, suggesting that more extensive genotoxic evaluations must be done to properly assess the genotoxic hazard of these nanomaterials.
Subject(s)
DNA Damage/drug effects , Graphite/pharmacology , Intestines/drug effects , Permeability/drug effects , Biological Transport/drug effects , Caco-2 Cells/drug effects , Cell Differentiation/drug effects , Cell Survival/drug effects , Graphite/chemistry , HT29 Cells , Humans , Intestinal Mucosa/drug effects , Nanoparticles/chemistry , Nanostructures/chemistry , Tight Junctions/drug effectsABSTRACT
It is common to find abundant genetic variation in host resistance and parasite infectivity within populations, with the outcome of infection frequently depending on genotype-specific interactions. Underlying these effects are complex immune defenses that are under the control of both host and parasite genes. We have found extensive variation in Drosophila melanogaster's immune response against the parasitoid wasp Leptopilina boulardi. Some aspects of the immune response, such as phenoloxidase activity, are predominantly affected by the host genotype. Some, such as upregulation of the complement-like protein Tep1, are controlled by the parasite genotype. Others, like the differentiation of immune cells called lamellocytes, depend on the specific combination of host and parasite genotypes. These observations illustrate how the outcome of infection depends on independent genetic effects on different aspects of host immunity. As parasite-killing results from the concerted action of different components of the immune response, these observations provide a physiological mechanism to generate phenomena like epistasis and genotype-interactions that underlie models of coevolution.