Genotoxic Effects Research Articles

Enhancing Selectivity and Inhibitory Effects of Chemotherapy Drugs Against Myelogenous Leukemia Cells with Lippia alba Essential Oil Enriched in Citral.

Acute myelogenous leukemia (AML) is one of the most lethal cancers, lacking a definitive curative therapy due to essential constraints related to the toxicity and efficacy of conventional treatments. This study explores the co-adjuvant potential of Lippia alba essential oils (EO) for enhancing the effectiveness and selectivity of two chemotherapy agents (cytarabine and clofarabine) against AML cells. EO derived from L. alba citral chemotype were produced using optimized and standardized environmental and extraction protocols. Rational fractionation techniques were employed to yield bioactive terpene-enriched fractions, guided by relative chemical composition and cytotoxic analysis. Pharmacological interactions were established between these fractions and cytarabine and clofarabine. The study comprehensively evaluated the cytotoxic, genotoxic, oxidative stress, and cell death phenotypes induced by therapies across AML (DA-3ER/GM/EVI1+) cells. The fraction rich in citral (F2) exhibited synergistic pharmacological interactions with the studied chemotherapies, intensifying their selective cytotoxic, genotoxic, and pro-oxidant effects. This shift favored transitioning from necrosis to a programmed cell death phenotype (apoptotic). The F2-clofarabine combination demonstrated remarkable synergistic anti-leukemic performance while preserving cell integrity in healthy cells. The observed selective antiproliferative effects may be attributed to the potential dual prooxidant/antioxidant behavior of citral in L. alba EO.

Anti-Inflammatory, Cytotoxic, and Genotoxic Effects of Soybean Oligopeptides Conjugated with Mannose.

Soy protein is considered to be a high-quality protein with a range of important biological functions. However, the applications of soy protein are limited due to its poor solubility and high level of allergenicity. Its peptides have been of interest because they exert the same biological functions as soy protein, but are easier to absorb, more stable and soluble, and have a lower allergenicity. Moreover, recent research found that an attachment of chemical moieties to peptides could improve their properties including their biodistribution, pharmacokinetic, and biological activities with lower toxicity. This study therefore aimed to acquire scientific evidence to support the further application and safe use of the soybean oligopeptide (OT) conjugated with allulose (OT-AL) or D-mannose (OT-Man). The anti-inflammation, cytotoxicity, and genotoxicity of OT, OT-AL, and OT-Man were investigated. The results showed that OT, AL, Man, OT-AL, and OT-Man at doses of up to 1000 µg/mL were not toxic to HepG2 (liver cancer cells), HEK293 (kidney cells), LX-2 (hepatic stellate cells), and pre- and mature-3T3-L1 (fibroblasts and adipocytes, respectively), while slightly delaying the proliferation of RAW 264.7 cells (macrophages) at high doses. In addition, the oligopeptides at up to 800 µg/mL were not toxic to isolated human peripheral blood mononuclear cells (PBMCs) and did not induce hemolysis in human red blood cells (RBCs). OT-Man (200 and 400 µg/mL), but not OT, AL, Man, and OT-AL, significantly reduced the production of NO and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) stimulated by lipopolysaccharide (LPS) in RAW 264.7 cells, suggesting that the mannose conjugation of soy peptide had an inhibitory effect against LPS-stimulated inflammation. In addition, the secretion of interleukin-6 (IL-6) stimulated by LPS was significantly reduced by OT-AL (200 and 400 µg/mL) and OT-Man (400 µg/mL). The tumor necrosis factor-α (TNF-α) level was significantly decreased by OT (400 µg/mL), AL (400 µg/mL), OT-AL (200 µg/mL), and OT-Man (200 and 400 µg/mL) in the LPS-stimulated cells. The conjugation of the peptides with either AL or Man is likely to be enhance the anti-inflammation ability to inhibit the secretion of cytokines. As OT-Man exhibited a high potential to inhibit LPS-induced inflammation in macrophages, its mutagenicity ability was then assessed in bacteria and Drosophila. These findings showed that OT-Man did not trigger DNA mutations and was genome-safe. This study provides possible insights into the health advantages and safe use of conjugated soybean peptides.

Study of genotoxic and neurotoxic effects of pesticides in rural workers and residents in the state of Rio de Janeiro/Brazil

Study of genotoxic and neurotoxic effects of pesticides in rural workers and residents in the state of Rio de Janeiro/Brazil

Impact of environmental concentrations of fipronil on DNA integrity and brain structure of Bombus atratus bumblebees

Fipronil (FP) is an insecticide used in the treatment and control of pests, but it also adversely affects bees. Currently, there is no data on the genotoxic effects of FP in the brain of bumblebees. Thus, through the comet assay and routine morphological analysis, we analyzed the morphological effects and potential genotoxicity of environmentally relevant concentrations of FP on the brain of Bombus atratus. Bumblebees were exposed at concentrations of 2.5 μg/g and 3.5 μg/g for 96 hours. After the exposure, the brains were removed for morphological and morphometric analysis, and the comet assay procedure - used to detect DNA damage in individual cells using electrophoresis. Our data showed that both concentrations (2.5 μg/g and 3.5 μg/g) caused DNA damage in brain cells. These results corroborate the morphological data. We observed signs of synapse loss in the calyx structure, intercellular spaces between compact inner and non-compact inner cells, and cell swelling. This study provides unprecedented evidence of the effects of FP on DNA and cellular structures in the brain of B. atratus and reinforces the need to elucidate its toxic effects on other species to allow future risk assessments and conservation projects.

Multiple-biomarker approach in the assessment of bisphenol A effect on the grooved carpet clam Ruditapes decussatus (Linnaeus, 1758)

BackgroundBisphenol A (BPA), a plastic additive monomer, is among the most highly produced chemicals worldwide, and is broadly used in many industries, such as food and beverage containers, milk bottles, and paper products. Previous studies demonstrated that BPA has potential toxicity to aquatic organisms, causing endocrine disturbance and behavioural disorders. The current work aimed to determine the toxic impacts of BPA on the edible marine clam Ruditapes decussatus considering a multi-biomarker approach (mortality, biochemical studies, DNA strand breaks using comet assay, and histopathological examinations with semi-quantitative and quantitative histopathological analyses). The clams were exposed under laboratory conditions to three concentrations of BPA (0 “control”, 1, and 5 µg/L) for a period of 21 days. After the exposure period, BPA impacts were assessed in the digestive gland as a versatile and environmentally relevant organ for ecotoxicological studies.ResultsIn BPA-treated clams, mortality (10%) occurred only at the highest BPA concentration (5 µg/L). Biochemical impairments were detected in a concentration-dependent manner as a consequence of BPA exposure. There were significant increases in malondialdehyde (MDA) and glutathione (GSH) levels, while catalase (CAT) activity was significantly reduced. Our results revealed that BPA induced neurotoxicity in R. decussatus, as evidenced by the inhibition of acetylcholinesterase (AChE) activity in a dose-dependent manner. Furthermore, DNA damage was strongly induced as BPA levels increased. Additionally, our results have been affirmed by alterations in digestive gland tissues at BPA treatments, which consequently can impair the clam’s ability for food absorption; these alterations included mainly atrophic and necrotic digestive tubules, epithelial cell vacuolization, hemocyte infiltration, and intertubular fibrosis. Based on the data obtained from the semi-quantitative and quantitative histopathological analyses, the exposure of the clam’s digestive gland to BPA with concentrations of 1 and 5 µg/L for 21 days showed significant histopathological alterations compared with the control clams.ConclusionThe multi-biomarker approach used in the current study proved to be a useful tool for assessing the impact of diphenylmethane compounds, such as BPA. Water-borne BPA causes oxidative stress, neurotoxicity, genotoxicity, and deleterious effects on the clam digestive gland; all of these could deteriorate clam performance and health, causing tissue dysfunction.

An evidence based comprehensive review on thiacloprid, a pesticide residue, induced toxicity: Unveiling hazard to human health

Thiacloprid, a hazardous neonicotinoid insecticide, prevalent in daily agricultural practices, raises concerns due to the harmful effects of its residues on food items, and on unintended organisms poses a significant threat to human health. Introduced in 1990, Thiacloprid have gained popularity for its perceived effectiveness and reduced risks to non-target animals. However, emerging research in recent years reports significant toxic effects of Thiacloprid on non-target species, spanning neurotoxicity, immunotoxicity, hepatotoxicity, nephrotoxicity, and reproductive issues. Mammalian studies, particularly involving rodents, reveal cognitive impairment, hippocampal damage, and hepatic abnormalities upon Thiacloprid exposure. Reproductive toxicity and DNA damage are imminent concerns, disrupting gestational epigenetic reprogramming and suggesting persistent effects on future generations. Genotoxic effects, Embryotoxic, and observed reproductive toxicity accentuate the need for caution in the utilization of Thiacloprid. This review highlights reported toxic effects produced by Thiacloprid in recent years, challenging the initial belief in its lower toxicity for vertebrates.

Investigation of genotoxicity induced by intermediate frequency magnetic field combined with ionizing radiation: In vitro study on human fibroblast cells

These days, exposure to electromagnetic fields has become omnipresent in modern society. Not only the extremely-low frequency and radiofrequency, but also intermediate frequency (IF) magnetic field (MF) might be absorbed in the human body resulting in an ever-growing concern about their possible health effects. Devices, such as induction cooktops, chargers, compact fluorescent lamps, touchscreens and electric vehicles emit a wide range of intermediate frequency fields. We investigated the effects of 22 kHz or 250 kHz intermediate frequency magnetic field exposure on the human skin cells. We also examined the adaptive response phenomenon; whether IF MF exposure could possibly reduce the harmful genotoxic effects of ionizing radiation. To get answers to these questions, in vitro studies were carried out on fibroblast cells to investigate the effects on oxidative stress, DNA damage and micronucleus formation. We found a decreased micronucleus formation due to the 22 kHz IF MF exposure and significantly increased oxidative stress in fibroblast cells, which were exposed only to 250 kHz IF MF. We were unable to detect the protective or co-genotoxic effects of intermediate frequency magnetic field exposure combined with ionizing radiation, thus we found no evidence for the adaptive response phenomena.

Human next-generation risk assessment of trichothecene toxicity

Trichothecenes are naturally occurring chemicals, produced by fungi, that can be found in contaminated crops. Trichothecenes have the potential to indirectly damage DNA and exacerbate genotoxic effects of genotoxicants. However, genotoxicity data for most trichothecenes are limited and data gaps remain. Here we use the γH2AX/pH3 assay to evaluate DNA damage in vitro of 13 trichothecenes. Three human cell lines (SH-SY5Y, ACHN, and HepG2) were exposed to each trichothecene (0.001–100 μM) to assess toxicity as models for the brain, kidney, and liver, respectively. Concentration-dependent induction of DNA damage, illustrated by γH2AX induction, was observed for all trichothecenes. In vitro-in vivo extrapolation (IVIVE) modeling was employed to support in vivo equivalent potency ranking and screen for risk potential. Diacetoxyscirpenol, T-2, and HT-2 had the highest genotoxic potency, notably in SH-SY5Y cells. Administered equivalent doses (AEDs) derived from IVIVE were compared against exposure data from French total diet studies to assess risk potential. AEDs derived for T-2 and HT-2 from the SH-SY5Y model were within 100-fold of exposure levels for infants aged one year or less. Overall, the potential for trichothecenes to damage DNA and higher exposures in infants highlights the need to investigate the cumulative effects across the broader trichothecene family.

Cyto- and genotoxicity evaluation of water samples collected from two rivers in the Kosovo.

River water in Kosovo is exposed to various discharges from industrial and agricultural activities as well as to urban wastewater. Rivers Sitnica and Drenica are among the most affected ones and water samples drawn from these rivers show the presence of various toxic substances. Genotoxic effects are seen in fish living in these rivers indicating a cytotoxic and mutagenic potential of the river water. Aiming at substantiating these observations, we assessed cyto- and genotoxic effects of water samples collected at different locations from Drenica and Sitnica river. Samples drawn from Lake Badovc served for comparison. To address seasonal effects, samples were collected at different seasons/time points during the period summer 2016 - spring 2018. The water samples were analyzed employing primary rat hepatocytes as reliable in vitro cell model for the assessment of cytotoxic effects (mitotic arrest and cell death) and DNA damage/genotoxicity (micronucleus assay, Comet assay). The results do not account for significant effects associated with specific locations but demonstrate seasonal differences of the genotoxic potential of the water samples collected along both rivers, which are accompanied by a limited cytotoxic potential. Our data provide substantial support to earlier observations and strongly warrant the need for continuous chemical as well as biological monitoring of the river water in Kosovo, focusing on an improved toxicant profiling of the river water and investigations addressing the observed seasonal variations.

Dietary oxyclozanide influences antioxidant enzyme activities and damages DNA in Galleria mellonella (Lepidoptera: Pyralidae).

Oxyclozanide (OXY) is an anthelmintic widely used in the treatment of flatworm infection and fasciolosis. It also has antiadenovirus, antibiofilm, antifungal, and antibacterial activities. Various chemicals have been suggested as alternative chemicals in insect pest management. Here, the oxidative and genotoxic effects of OXY on 7th instars, pupae and adults of the model organism Galleria mellonella (Linnaeus) (Lepidoptera: Pyralidae) were examined. First-instar larvae were reared on 0.003, 0.03, 0.3, and 1.5 g OXY per 100 g artificial diets. Compared with all tested OXY concentrations and controls without OXY, dietary OXY led to increased antioxidant capacity and genotoxic effects. Concentrations of malondialdehyde, an oxidative stress marker, were significantly increased in adults of larvae reared on OXY-charged diets at 0.3 and 1.5 g/100 g compared to the adult control group. We also recorded a significant increase in the genotoxic test data (Tail length, Tail DNA %, Tail moment) at the same stages and concentrations. We recorded significant increases in glutathione-S-transferase, superoxide dismutase (SOD) and glutathione peroxidase activities in larvae fed high OXY concentrations. SOD and catalase activities were also significantly increased at the concentration of 0.03 g/100 g of OXY in the pupal and adult stages. Cytochrome P450 monooxygenase activity was significantly increased at the highest concentration of OXY in the larval and pupal stages. Also, our regression analysis indicates a correlation between the markers of oxidative stress, antioxidant enzymes and comet parameters. These data indicate that OXY induces oxidative stress and antioxidative enzyme response.

Cytotoxic and genotoxic effects of tert-butylhydroquinone, butylated hydroxyanisole and propyl gallate as synthetic food antioxidants.

Synthetic food antioxidants such as tert-butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA), and propyl gallate (PG) have been extensively utilized in different food industries because of their high protectant activities to stop food spoilage and remove foodborne diseases in humans and animals. It would be emphasized that increasing the intake of antioxidants through intracellular may lead to cyto/genotoxicity, and their complex formation with biological molecules eventually accelerate the progress of various diseases like multiple sclerosis, diabetes, neurological disorders, cardiac vascular disease, cancer, etc. Therefore, their toxicity is one of the challenging subjects due to their extensive use in food-related industries. TBHQ, BHA, and PG antioxidants have cytotoxic, genotoxic, and carcinogenic effects if absorbed in high doses through the gastrointestinal tract. Thermodynamic parameters presented that the hydrophobic bind plays a key role in the complexation of the TBHQ, BHA, and PG with albumin. The molecular modeling results showed that subdomain IIA plays a vital role in the interaction of TBHQ and BHA with albumin. To comprehend the mechanisms of the cyto/genotoxicity effects of these food antioxidants and conformational alterations of albumin macromolecule, we aim to overview numerous types of research that evaluated the cyto/genotoxicity effects of these antioxidants using several procedures.

Allium cepa as a Toxicogenetic Investigational Tool for Plant Extracts: A Systematic Review.

Toxicological studies are important to investigate the genotoxic effects of various substances. Allium cepa can be used as test model for this purpose. This review summarizes the scope and applications for this A. cepa test model. For this, an up-to-date (April 2023) literature search was made in the Science Direct, PubMed, and Web of Science databases to find published evidence on studies performed using A. cepa as a test model. Out of 3,748 studies, 74 fit the inclusion criteria. The results showed that the use of the test model A. cepa contributed considerably to measuring the toxicological potential of plant extracts, proving the efficacy of the test as a potent bioindicator of toxic effects. In addition, 27 studies used more than one test system to verify the toxicological potential of extracts and fractions. Studies have shown that the A. cepa model has the potential to replace other test systems that make use of animals and cell cultures, besides having other advantages such as low cost, ease of execution, and good conditions for the observation of chromosomes. In conclusion, the A. cepa test can be considered one of the potential biomonitoring systems in toxicological studies of crude extracts.

Mechanistic insights into acetamiprid-induced genotoxicity on the myocardium and potential ameliorative role of resveratrol

The current study aimed to explore the genotoxic impacts of the insecticide acetamiprid (ACP) on the myocardium and assess the ameliorative role of resveratrol (RSV). Male rats (10/group) were treated via oral route for 90 days: control; ACP (25 mg/kg); RSV (20 mg/kg); ACP+RSV. Peripheral blood micronucleus test, oxidative stress analysis, comet assay, 8-hydroxydeoxyguanosine and gene expression assessment were performed. The findings revealed that ACP has myocardial genotoxic effects, as demonstrated by increased micronucleus and 8-hydroxydeoxyguanosine formation and increased all comet parameters. Oxidative stress analysis demonstrated that ACP elevated H2O2 and NO levels while decreasing catalase and GST activities. Acetamiprid dysregulated the expression of genes related to oxidative stress and DNA damage response. However, RSV co-treatment resulted in significant protection against these genotoxic impacts. Resveratrol reduced DNA damage and restored the oxidative balance in the myocardium. Moreover, RSV modulated the Nrf2/HO-1 and Atm/P53 pathways, potentiating antioxidant defense and DNA repair.

Direct and indirect toxicity mechanisms of the natural insecticide azadirachtin based on in-silico interactions with tubulin, topoisomerase and DNA

Natural pesticides, which attract attention with safe properties, pose a threat to many non-target organisms, so their toxic effects should be studied extensively. In this study, the toxic effects of Azadirachtin, a natural insecticide derived from Azadirachta indica, were investigated by in-vivo and in-silico methods. In-vivo toxic effects were determined using the Allium test and bulbs were treated with 5 mg/L (0.5x EC50), 10 mg/L (EC50), and 20 mg/L (2xEC50) Azadirachtin. In the groups treated with Azadirachtin, there was a decline in germination-related parameters and accordingly growth was delayed. This regression may be related to oxidative stress in the plant, and the increase in malondialdehyde and proline levels in Azadirachtin-applied groups confirms oxidative stress. Azadirachtin toxicity increased dose-dependently and the most significant toxic effect was observed in the group administered 20 mg/L Azadirachtin. In this group, the mitotic index decreased by 43.4% and sticky chromosomes, vagrant chromosomes and fragments were detected at rates of 83.1 ± 4.01, 72.7 ± 3.46 and 65.1 ± 3.51, respectively. By comet analysis, it was determined that Azadirachtin caused DNA fragmentation, and tail DNA, which was 0.10 ± 0.32% in the control group, increased to 34.5 ± 1.35% in the Azadirachtin -treated groups. These cytotoxic and genotoxic effects of Azadirachtin may be due to direct interaction with macromolecules as well as induced oxidative stress. Azadirachtin has been found to interact in-silico with alpha-tubulin, beta-tubulin, topoisomerase I and II, and various DNA sequences. Possible deteriorations in macromolecular structure and functions as a result of these interactions may cause cytotoxic and genotoxic effects. These results suggest that natural insecticides may also be unreliable for non-target organisms, and the toxic effects of compounds presented as “natural” should also be investigated.

Abstract Mo075: Cigarette smoking causes somatic mutations in cardiac endothelial cells

Cigarette smoking (CS) is a major contributor to cardiovascular diseases (CVDs), responsible for one in every four CVD-related deaths. Despite this, the precise mechanisms through which smoking induces CVDs remain elusive. The chemicals in cigarette smoke, particularly oxidants, are known to instigate oxidative stress and activate the vessel wall. Alongside the dysregulation of cellular functions, oxidative stress can lead to DNA damage. Accumulation of DNA damage and somatic mutations is a recognized hallmark of aging, a significant risk factor for various age-related diseases, including CVDs, neurodegenerative diseases, and cancer. Recent studies have indicated a substantial increase in somatic mutations, with mutational signatures reflective of oxidative stress, in bronchial epithelial cells from smokers. Given their proximity in the blood circulation, these pathophysiological findings could naturally extend to the coronary system. Therefore, we hypothesized that CS induces somatic mutations and injuries in cardiac endothelial cells (ECs), laying the mechanisms for cigarette smoking-induced CVDs. To test this hypothesis, we conducted single-cell whole-genome sequencing (scWGS) on 105 cardiac endothelial cells isolated from postmortem hearts of 6 normal individuals, 3 smokers, and 4 smokers with atherosclerotic cardiovascular disease (ASCVD). Our results revealed a significant increase in somatic single nucleotide variants (SNVs) and insertions and deletions (indels) in cardiac ECs from smokers and those with ASCVD. These excess somatic mutations exhibited Catalogue Of Somatic Mutations In Cancer (COSMIC) mutational signatures, including SBS4, SBS29, SBS40, SBS92, and ID3, indicative of DNA damage and mutagenesis associated with cigarette smoking, oxidative stress, and formaldehyde exposure. Further analysis of single-nucleus RNA sequencing (snRNA-seq) data from postmortem hearts of 3 normal individuals, 4 smokers, and 1 smoker with ASCVD demonstrated upregulated pathways involved in apoptosis, EC migration, and vascular development. In conclusion, our study demonstrates that chemicals in cigarette smoke exert direct genotoxic effects on cardiac ECs, mirroring their impact on bronchial epithelial cells. Cigarette smoking significantly accelerates the accumulation of somatic mutations in cardiac ECs, resulting in apoptosis and vascular damage. Consequently, this damage leads to a secondary activation of angiogenesis for vascular repair.

Toxicity of zinc oxide nanoparticles: Cellular and behavioural effects

Due to their extensive use, the release of zinc oxide nanoparticles (ZnO NP) into the environment is increasing and may lead to unintended risk to both human health and ecosystems. Access of ZnO NP to the brain has been demonstrated, so their potential toxicity on the nervous system is a matter of particular concern. Although evaluation of ZnO NP toxicity has been reported in several previous studies, the specific effects on the nervous system are not completely understood and, particularly, effects on genetic material and on organism behaviour are poorly addressed. We evaluated the potential toxic effects of ZnO NP in vitro and in vivo, and the role of zinc ions (Zn2+) in these effects. In vitro, the ability of ZnO NP to be internalized by A172 glial cells was verified, and the cytotoxic and genotoxic effects of ZnO NP or the released Zn2+ ions were addressed by means of vital dye exclusion and comet assay, respectively. In vivo, behavioural alterations were evaluated in zebrafish embryos using a total locomotion assay. ZnO NP induced decreases in viability of A172 cells after 24 h of exposure and genetic damage after 3 and 24 h. The involvement of the Zn2+ ions released from the NP in genotoxicity was confirmed. ZnO NP exposure also resulted in decreased locomotor activity of zebrafish embryos, with a clear role of released Zn2+ ions in this effect. These findings support the toxic potential of ZnO NP showing, for the first time, genetic effects on glial cells and proving the intervention of Zn2+ ions.

Genotoxic effects of copper nanoparticles on Vicia pannonica Crantz. root meristem cells

With the increasing use of metal nanoparticles, their access to the food chain has become the main concern for scientists. The present study sheds light on the copper nanoparticles (Cu NPs), which are widely used in many industries today. For this purpose, Vicia pannonica Crantz., a common fodder plant, was used and exposed to metal-based Cu NPs. To determine the genotoxic effects on root meristem cells, total of 3 different concentrations (50 ppm, 150 ppm, and 300 ppm) of Cu NPs and the control in deionized water solutions were prepared. The determination of the accumulation and elimination of Cu NPs in Vicia pannonica used in the study was carried out using with X-ray diffraction (XRD), scanning electron microscopy (SEM), SEM element mapping, and energy dispersive X-ray diffraction (EDS) characteristic spectrum analysis. All doses of Cu NPs caused significant decreases in the Mitotic index of V. pannonica meristem cells compared to the control. Multiple analyzes carried out in the study showed that Cu NPs caused abnormalities in cell division such as C-metaphase, polar aberration, deconstructed anaphase, chromosome breakage, loss of genetic material, failure to assemble in the metaphase plate, deconstructed metaphase, asynchronous division remaining chromosome in metaphase, adhesion, deconstructed prophase, advanced chromosomes, and chromosome bridges in anaphase. Results support that Cu NPs have a genotoxic effect on V. pannonica.

Biosynthesis and characterization of gold nanoparticles from citrullus colocynthis (L.) schrad pulp ethanolic extract: Their cytotoxic, genotoxic, apoptotic, and antioxidant activities

The age-old discipline of plant therapy has gained renewed importance through the utilization of plants for the synthesis of metal nanoparticles. However, toxicity testing and characterization of the recently synthesized nanomaterials are essential to evaluating their appropriate application. Citrullus colocynthis is a medicinal plant with several health benefits. Herein, we used its ethanolic pulp extract (PE) to manufacture gold nanoparticles (PE-AuNPs). Various approaches were employed to assess the MTT50 and NR50 values of PE and PE-AuNPs at different concentrations in the human hepatocarcinoma cell line (HepG2). The study aimed to assess the genotoxic effects and in vivo toxicity of PE and PE-AuNPs at MTT50 dosages. The quasi-spherical, cubic/triangular prisms, and nail-looking particles exhibited no antioxidant properties. They had an absorbance peak between 540 and 560 nm, diameters of less than 20 nm, hydrodynamic diameters of 177.9 nm, and a negative surface charge (−10.3 mV). The significant role of plant phytochemicals in the formation of metal nanoparticles is confirmed by the diminished antioxidant capacity of extract residues following PE-AuNP synthesis. PE-AuNPs exhibited in vivo and cytotoxic effects at relatively lower concentrations compared to PE. In contrast to PE, PE-AuNPs exhibited lower genotoxic at MTT50 dosages. Despite having MTT50 values of approximately 1.95 ± 0.06 and 0.89 ± 0.03 mg/ml, PE and PE-AuNPs can still be considered biocompatible. Nonetheless, our results suggest that the characteristics of recently produced nanoparticles can differ from those of the matching plant. Further investigation can provide a better understanding of the possible therapeutic and pharmacological impacts of PE-AuNPs.

Study of genotoxic and cytotoxic effects induced in human fibroblasts by exposure to pulsed and continuous 1.6 GHz radiofrequency.

The widespread use of radiofrequency (RF) sources, ranging from household appliances to telecommunications devices and military equipment, raises concerns among people and regulatory agencies about the potential health risks of RF exposure. Consequently, several in vitro and in vivo studies have been done to investigate the biological effects, in particular non-thermal, of this non-ionizing radiation. To date, this issue is still being debated due to the controversial results that have been reported. Furthermore, the impact of different RF signal modulations on biological systems remains poorly investigated. The present in vitro study aims to evaluate the cytotoxicity and genotoxicity of continuous or pulsed 1.6 GHz RF in human dermal fibroblasts (HDF). HDF cultures were exposed to continuous and pulsed 1.6 GHz RF, for 2 h, with Specific Absorption Rate (SAR) of 0.4 W/kg. The potential biological effects of 1.6 GHz RF on HDF were assessed with a multi-methodological approach, analyzing the effects on cell cycle, ultrastructure, protein expression, mitotic spindle, CREST stained micronuclei, chromosome segregation and γ-H2AX/53BP1 foci. 1.6 GHz RF exposure modified proteins expression and morphology of HDF. Specifically, the expression of different heat-shock proteins (HSP) (i.e., HSP-90, HSP-60, and HSP-25) and phospho-AKT were affected. In addition, both continuous and pulsed RF modified the cytoskeletal organization in HDF and increased the number of lysosomes, while the formation of autophagosomes was observed only after pulsed RF exposure. Mitotic spindle anomalies were also found after exposure. However, no significant effect was observed on cell cycle, chromosome segregation, CREST-stained micronuclei and γ-H2AX/53BP1 foci. The results of the present study show the absence of genotoxic damage in 1.6 GHz RF exposed HDF and, although mitotic spindle alterations were observed, they did not have an aneugenic effect. On the other hand, changes in some proteins expression and cell ultrastructure in exposed HDF suggest that RF can potentially induce cell alterations at the morphological and molecular levels.

Assessment of cytotoxic and genotoxic effects of glyphosate-based herbicide on glioblastoma cell lines: Role of p53 in cellular response and network analysis

Glyphosate, the world's most widely used herbicide, has a low toxicity rating despite substantial evidence of adverse health effects. Furthermore, glyphosate-based formulations (GBFs) contain several other chemicals, some of which are known to be harmful. Additionally, chronic, and acute exposure to GBFs among rural workers may lead to health impairments, such as neurodegenerative diseases and cancer. P53 is known as a tumor suppressor protein, acting as a key regulator of the cellular response to stress and DNA damage. Therefore, mutations in the TP53 gene, which encodes p53, are common genetic alterations found in various types of cancer. Therefore, this study aimed to evaluate the cytotoxicity and genotoxicity of GBF in two glioblastoma cell lines: U87MG (TP53-proficient) and U251MG (TP53-mutant). Additionally, the study aimed to identify the main proteins involved in the response to GBF exposure using Systems Biology in a network containing p53 and another network without p53. The MTT assay was used to study the toxicity of GBF in the cell lines, the clonogenic assay was used to investigate cell survival, and the Comet Assay was used for genotoxicity evaluation. For data analysis, bioinformatics tools such as String 12.0 and Stitch 5.0 were applied, serving as a basis for designing binary networks in the Cytoscape 3.10.1 program. From the in vitro test analyses, it was observed a decrease in cell viability at doses starting from 10 ppm. Comet Assay at concentrations of 10 ppm and 30 ppm for the U251MG and U87MG cell lines, respectively observed DNA damage. The network generated with systems biology showed that the presence of p53 is important for the regulation of biological processes involved in genetic stability and neurotoxicity, processes that did not appear in the TP53-mutant network.