Genotoxic Potential Research Articles

A Comprehensive Review on Preparation of Silver Nanoparticles from a Bacteriocin for the Natural Preservation of Food Products.

Food preservation aims to maintain safe and nutritious food for extended periods by inhibiting microbial growth that causes spoilage and poses health risks. Traditional chemical preservatives like sodium sulfite, sodium nitrite, sodium benzoate, tBHQ and BHA have raised concerns due to potential carcinogenicity, genotoxicity and allergies with long-term consumption. As a natural alternative, bacteriocins have emerged for food preservation. These ribosomally synthesised antimicrobial peptides are produced by various microorganisms, including bacteria, fungi and yeast, typically during their stationary growth phase. Bacteriocins are categorised into four classes based on structure and function, with molecular weights averaging between 30 and 80kDa. They exhibit antimicrobial activity against a range of bacteria, mediating complex interactions between bacterial species and enhancing competitiveness and survival of producer strains. Both gram-positive and gram-negative bacteria produce bacteriocins. Recent advancements have identified and optimized bacteriocins for applications in food technology, extending shelf life, managing foodborne illnesses and contributing to public health preservation. Their eco-friendly nature and safety profile make bacteriocins promising for future food preservation strategies without detrimental effects on humans or animals. The current review has mainly focused on the preservation of food products using bacteriocin.

AuNPs-based lateral flow strip genotoxicity biosensor by sensitive quantification of 8-oxodGuo

Development of rapid and sensitive methods for screening of large number of chemical pollutants with potential genotoxicity is in urgent demands. In this work, we reported a chemical genotoxicity sensor based on the lateral flow strip (LFS) quantification of the 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo). The proposed sensing strategy introduced human 8-oxoguanine DNA glycosylase (hOGG 1) and human apyrimidinic endonuclease (APE 1) to convert 8-oxodGuo to strand break. Then, the DNA conjugated gold nanoparticles (AuNPs) complexes could not be captured on test line (T-line), showing visible red color fading. Additionally, the mean grey value of the optical density in the T-line zone was analyzed by using a mobile phone camera and Image J software to quantify 8-oxodGuo. Under the optimized experimental conditions, the LFS DNA biosensor could detect the lowest concentration of 8-oxodGuo down to 0.2 pmol. To demonstrate its universal applications, in vitro generation of 8-oxodGuo by Rose Bengal under irradiation and Fe2+-mediated Fenton reagent were successfully measured. The detection limit of oxidative DNA damage induced by Rose Bengal or Fenton reagent could be down to 0.01 μM or 1 nM Fe2+/4 nM H2O2, respectively. The 10-fold higher sensitivity for Fenton reagent was attributed to much more severe damage than Rose Bengal, producing both DNA strand break and nucleobases conversion. The results demonstrated that the LFS DNA biosensor could detect oxidative DNA damage for the first time, showing its potential application for assessment of the genotoxicity of abundant chemical pollutants.

Designing of amiloride loaded citrate functionalized amorphous silica nanoparticles to investigate its genotoxic and cytotoxic potential

In the present work, silica-based nanocarrier for the anticancer drug, amiloride have been synthesized and characterized using various physicochemical techniques. The aim of this work emphasis on investigating the physicochemical properties and cytotoxic effects of citrate-functionalized amiloride loaded silica nanoparticles. Silica nanoparticles synthesis was carried out via condensation reaction, then coated by tris sodium citrate, followed by their functionalization using amiloride through EDC-NHS reaction. SEM and HR-XRD analysis indicated the formation of amorphous spherical silica nanoparticles. The existence of citrate coating was evident from FT-IR and TGA results, which were supported by DLS and zeta potential studies. The formation of amiloride conjugated citrate coated silica nanoparticles (SiNPs-Cit@Ami) was confirmed by the DLS, Zeta potential and UV-Visible spectroscopy. Size of SiNPs-Cit@Ami nanoparticles was found to be around 80nm using TEM. Additionally, these nanoparticles showed high loading efficiency and time-dependent release of amiloride. DNA binding studies were examined using UV–Visible, Fluorescence spectroscopic and Competitive fluorescence studies. The results indicate that SiNPs-Cit@Ami bind to Ct-DNA via minor groove binding mode. Furthermore, the cytotoxic effect of SiNPs-Cit@Ami on HepG2 cell lines was found to be higher than amiloride alone. Our findings suggest that SiNPs-Cit@Ami can be employed as a promising candidate for cancer mitigation.

In vitro cyto- and geno-toxicity of asbestiform erionite from New Zealand

This work is an in vitro toxicity study of two asbestiform erionites from Kaipara and Gawler Downs in New Zealand. This study is the first, to the knowledge of the authors, to investigate the mechanisms that trigger adverse effects leading to carcinogenicity from New Zealand erionites. The effects induced by the erionite fibres from New Zealand were compared with those produced by positive (crocidolite) and negative (wollastonite) standards, and other erionite fibres described in the literature. The cytotoxicity/genotoxicity/inflammatory potential was determined by: (i) analysis of the cytotoxic potential by MTT tests on human cell lines mimicking primary cells making direct contact with fibres in the lungs, combined with apoptosis tests and cell membrane damage by fluorescence microscopy analyses; (ii) analysis of the genotoxic potential by quantification of DNA damage measuring double strand break foci by γ-H2AX nuclear staining in confocal microscopy analyses; (iii) analyses of the acute (24–72h) and early-chronic (7d) inflammatory effect by gene expression analyses of several cytokines, as well as of fibrotic and Epithelial to Mesenchymal transition (EMT) markers. The intensity of cell responses to these erionites are comparable to that of standard carcinogenic crocidolite, indicating that the two erionite fibres exhibit a significant acute toxic potential, with a particular alarming effect from the Gawler Downs sample from South Island. Our results confirm that the investigated erionites from New Zealand may represent an environmental hazard. However, further investigation is required to determine potential environmental exposure pathways by which erionite may become airborne and assess any environmental risks that may arise.

Local QSAR based on quantum chemistry calculations for the stability of nitrenium ions to reduce false positive outcomes from standard QSAR systems for the mutagenicity of primary aromatic amines

BackgroundPrimary aromatic amines (PAAs) present significant challenges in the prediction of mutagenicity using current standard quantitative structure activity relationship (QSAR) systems, which are knowledge-based and statistics-based, because of their low positive prediction values (PPVs). Previous studies have suggested that PAAs are metabolized into genotoxic nitrenium ions. Moreover, ddE, a relative-energy based index derived from quantum chemistry calculations that measures the stability nitrenium ions, has been correlated with mutagenicity. This study aims to further examine the ability of the ddE-based approach in improving QSAR mutagenicity predictions for PAAs and to develop a refined method to decrease false positive predictions.ResultsInformation on 1,177 PAAs was collected, of which 420 were from public databases and 757 were from in-house databases across 16 laboratories. The total dataset included 465 Ames test-positive and 712 test-negative chemicals. For internal PAAs, detailed Ames test data were scrutinized and final decisions were made using common evaluation criteria. In this study, ddE calculations were performed using a convenient and consistent protocol. An optimal ddE cutoff value of -5 kcal/mol, combined with a molecular weight ≤ 500 and ortho substitution groups yielded well-balanced prediction scores: sensitivity of 72.0%, specificity of 75.9%, PPV of 65.6%, negative predictive value of 80.9% and a balanced accuracy of 74.0%. The PPV of the ddE-based approach was greatly reduced by the presence of two ortho substituent groups of ethyl or larger, as because almost all of them were negative in the Ames test regardless of their ddE values, probably due to steric hindrance affecting interactions between the PAA and metabolic enzymes. The great majority of the PAAs whose molecular weights were greater than 500 were also negative in Ames test, despite ddE predictions indicating positive mutagenicity.ConclusionsThis study proposes a refined approach to enhance the accuracy of QSAR mutagenicity predictions for PAAs by minimizing false positives. This integrative approach incorporating molecular weight, ortho substitution patterns, and ddE values, substantially can provide a more reliable basis for evaluating the genotoxic potential of PAAs.

Cytogenetic and photosynthetic responses of plants after exposure to water from a lake environment.

Plants are sensitive to environmental pollutants and are excellent organisms for genetic and physiological testing. Plant-based test systems are often used to study aquatic, aerial, and terrestrial pollution, especially Allium cepa, but studies with Tradescatia pallida specimens have gained prominence due to their sensitivity and applicability. Among the biomarkers, cytogenetic damage and chlorophyll levels are used in stress studies due to their responses to single or combined factors. The aim of this study was to evaluate cytogenetic and photosynthetic responses in T. pallida, and cytogenetic responses in A. cepa exposed to water from three sampling stations in the Juara lagoon (Municipality of Serra, ES, Brazil), collected in two sampling campaigns. The cytotoxic, genotoxic, and mutagenic potentials were analyzed using the T. pallida root tip mitosis assay and the Allium cepa test. Chloroplast pigment levels were measured in T. pallida leaves after chronic exposure to the lagoon water. The cytogenetic tests showed cytogenetic alterations at two sampling stations in at least one sampling campaign, suggesting the presence of potential pollutants, the effects of which were maximized during the rainy season. The study of photosynthetic metabolism in T. pallida showed a relationship between the levels of chloroplast pigments and the amount of nutrients present in the water.

Safety assessment and exploration of the mechanism of toxic effects of diallyl trisulfide: Based on acute and subacute toxicity and proteomics experiments

Ethnopharmacological relevanceGarlic (Allium sativum L.) is a widely consumed spice and condiment around the world, applied both as a food and as a traditional medicine, and is a natural strengthening agent for the body's circulatory and nervous systems. Diallyl trisulfide (DATS) is the major volatile organosulfur phytochemical found in garlic, with antithrombotic, anticoagulant, and antiplatelet activities as well as antioxidant, anti-infective, and other pharmacological effects. However, the safe dose and the underlying mechanisms of its toxic effects remain elusive. Aim of the studyDATS, an important pharmacologically active compound found in garlic, has garnered attention for its ability to fight cancer, antioxidant, anti-infective, and cardioprotective. The aim of this study was to evaluate the safety of DATS and to elucidate the potential mechanisms of its toxicity. Materials and methodsIn this study, ICR mice were selected for acute and subacute toxicity experiments according to OECD guidelines. The toxicity profile of DATS was analyzed by computer prediction software. Also, key differential proteins in spleen and serum were analyzed by proteomics. The binding stability of DAST to differential proteins was analyzed by molecular docking. Additionally, the regulatory relationship between DATS and differential proteins was verified by Western blot and ELISA experiments. ResultsThe results showed that the LD50 value of DATS in acute toxicity was 188.67 mg/kg. In subacute toxicity, water consumption and food intake were reduced in both male and female mice. In addition, the spleen and small intestinal organ coefficients were significantly elevated in male mice at the high dose of DATS; the blood biochemical indices ALB and TP were also significantly elevated. HE staining results showed significant damage to the spleen, liver, small intestine, and kidney of mice at high doses of DATS. Spleen and serum proteomics analyses showed that DATS significantly inhibited ZBP1 expression and upregulated TEC. ADMETlab 2.0 software predictions identified DATS as having potential genotoxicity, dermal sensitization, carcinogenicity, and respiratory and ocular toxicity. Docking results showed that the binding energies between DATS and TEC protein (PDB: 6F3F) and ZBP1 protein (PDB: 4KA4) were −3.7 kcal/mol, −2.4 kcal/mol, respectively. Western blot results showed that DATS-H significantly inhibited the expression of ZBP1 (only in male mice) and Bcl-2 proteins. ELISA results showed that DATS-H significantly increased the level of TEC protein both in male and female mice. ConclusionsLong-term administration of high-dose DATS may carry some risk of toxicity. Based on the amount of DATS in garlic, it is recommended that adults should not take more than 359 mg of DATS and 84.5 g of garlic per day. The mechanism of toxicity may be related to the fact that DATS significantly inhibits ZBP1 expression, upregulates TEC, and promotes apoptosis. This study provides valuable toxicological data for the effective evaluation of the long-term toxicity of DATS and offers an additional experimental basis for developing DATS as a healthy food or drug.

Nuclear abnormalities and DNA damage indicate different genotoxic stress responses of marsh frogs (Pelophylax ridibundus, Pallas 1771) to industrial and agricultural water pollution in South Bulgaria.

Amphibians are continuously exposed to pollutants and anthropogenic stressors in their natural habitats, representing a significant challenge to their survival. This study aimed to quantify the extent of DNA damage caused by chronic industrial and agrochemical surface water pollution in wild populations of the marsh frog (Pelophylax ridibundus). The observed genotoxic effects on the marsh frog DNA, manifesting as abnormalities in erythrocyte nuclei, micronuclei, and DNA strand breaks, demonstrate a clear cause-and-effect relationship with surface water parameters, heavy metals, metalloids, and pesticides. The most prevalent nuclear abnormalities observed were notched and blebbed nuclei and nuclear buds, indicative of chromosomal instability. The significant correlation between cadmium, lead, and copper contamination and the increased frequency of DNA breakage in the marsh frogs from the industrial site indicates that heavy metal contamination has a higher genotoxic potential than pesticide contamination. These findings underscore the vulnerability of amphibians inhabiting heavy metal-contaminated wetlands to genotoxic stress due to their lower tolerance to environmental genotoxins. Therefore, using in situ assays to detect erythrocyte nuclear abnormalities and DNA damage in P. ridibundus could serve as a reliable indicator of environmental quality and provide early detection of anthropogenic pollution.

Colibactin-driven colon cancer requires adhesin-mediated epithelial binding.

Various bacteria are suggested to contribute to colorectal cancer (CRC) development1-5, including pks+ Escherichia coli, which produces the genotoxin colibactin that induces characteristic mutational signatures in host epithelial cells6. However, it remains unclear how the highly unstable colibactin molecule is able to access host epithelial cells to cause harm. Here, using the microbiota-dependent ZEB2-transgenic mouse model of invasive CRC7, we demonstrate that the oncogenic potential of pks+ E. coli critically depends on bacterial adhesion to host epithelial cells, mediated by the type 1 pilus adhesin FimH and the F9 pilus adhesin FmlH. Blocking bacterial adhesion using a pharmacological FimH inhibitor attenuates colibactin-mediated genotoxicity and CRC exacerbation. We also show that allelic switching of FimH strongly influences the genotoxic potential of pks+ E. coli and can induce a genotoxic gain-of-function in the probiotic strain Nissle 1917. Adhesin-mediated epithelial binding subsequently allows the production of the genotoxin colibactin in close proximity to host epithelial cells, which promotes DNA damage and drives CRC development. These findings present promising therapeutic routes for the development of anti-adhesive therapies aimed at mitigating colibactin-induced DNA damage and inhibiting the initiation and progression of CRC, particularly in individuals at risk for developing CRC.

Novelties on tradescantia: Perspectives on water quality monitoring.

In the face of intense urban expansion, the assessment of water quality plays a crucial role in environmental preservation. Here, we evaluated aquatic genotoxicity in three locations with different degrees of urbanization using Tradescantia pallida var. purpurea and Daphnia magna as bioindicators. The objective was to investigate the influence of urbanization on water quality and the efficiency of the TRAD-MCN biological test in monitoring aquatic genotoxicity. Therefore, we established the genotoxic potential by evaluating micronucleus frequency in T. pallida and immobilization and DNA damage in the standard test with D. magna during two seasons of the year (dry and rainy). Our results showed that the frequency of micronuclei in T. pallida (TRAD-MCN) was significantly higher in the locations with a higher degree of urbanization, independently of the seasons. The tests with D. magna revealed a higher rate of immobilization and DNA damage in the location most impacted by residential and industrial effluents (especially mining activities). Additionally, the TRAD-MCN proved to be equivalent to the standard test for genotoxicity assessment, supporting its potential applicability in environmental monitoring. Finally, we observed that urbanization significantly influences water quality, and among the evaluated physicochemical parameters, dissolved oxygen was shown to be the most important driver of the water quality index (WQI). Our findings have significant implications for water resource management, underlining the need for policies that consider the specificities of different regions. This highlights the robustness, flexibility, and reliability of T. pallida as an environmental monitoring tool.

Genotoxic and Cytotoxic Activities of Cornhusk Extract of Zea mays and Leaf Extract of Sacharum officinarum

Zea mays husk and Saccharum officinarum have been used for years in ethnomedicine for their antimalarial, anti-inflammatory, antipyretic, antidiabetic, and antiphlogistic activities. The cytotoxic and genotoxic effects of Zea mays husk and Saccharum officinarum leaf extracts on the root meristem cells of Allium cepa were investigated. Onion bulbs were exposed to 2.5 mg/ml, 5mg/ml, and 10 mg/ml concentrations of the extracts for macroscopic and microscopic analysis. Tap water was used as a negative control and Methotrexate (0.1 mg/ml) was used as a positive control. There was statistically significant (p < 0.05) inhibition of root growth depending on concentration by the extracts when compared with the negative control group. All the tested extracts were observed to have cytotoxic effects on cell division in A. cepa. The extract induced chromosomal aberrations and micronuclei (MNC) formations in A. cepa root tip cells were significant (p<0.05) when compared with the control group. The extracts treatment further induced cell death, ghost cells, cells membrane damage, and binucleated cells. The Zea mays husk extract was found to exhibit higher cytotoxic and genotoxic potential than Saccharum officinarum leaf extract. These results suggest that Zea mays husk and Saccharum officinarum leaf extracts possess cytotoxic and genotoxic effects on A. cepa.

Evaluation of Genotoxic and Hemolytic Effects of Aphanizomenon flos-aquae and Microcystis aeruginosa Biomass Extracts on Human Blood Cells In Vitro.

This study explores the in vitro effects of cyanotoxins from the methanolic extract of the cyanobacteria Aphanizomenon flos-aquae and Microcystis aeruginosa on human blood cells, with samples drawn from the Gruža reservoir in Serbia. These cyanobacteria, which made up 98.5% of the reservoir's phytoplankton, reached densities of 4,656,450 cells mL-1, with A. flos aquae (3,105,120 cells mL-1) as the dominant species, followed by M. aeruginosa (1,480,130 cells mL-1). A cyanotoxin analysis of biomass detected anatoxin-a (3.56 µg g-1), cylindrospermopsin (6.86 µg g-1), microcystin LR (0.87 µg g-1), and microcystin RR (2.47 µg g-1). This study assessed the genotoxic potential of the methanolic extract of the cyanobacterial biomass by evaluating the DNA damage and the Genetic Damage Index (GDI) in peripheral blood lymphocytes (PBLs) from healthy donors. The results showed a dose-dependent increase in the DNA damage, from 35.67 ± 4.93% at 10 µg mL-1 to 95.67 ± 1.53% at 100 µg mL-1, with a corresponding rise in the GDI from 0.61 ± 0.02 to 2.39 ± 0.07. The extract also caused the concentration-dependent hemolysis of red blood cells, with 5.63% hemolysis at the highest concentration (200 µg mL-1). These findings underscore the significant genotoxic risks posed by cyanotoxins from biomass extracts of A. flos aquae and M. aeruginosa, particularly in water sources used for human consumption.

Study of acute and subacute toxicities and genotoxic and mutagenic potentials of the lyophilized extract of Campomanesia sessiliflora (O.Berg) mattos leaves in wistar rats

Campomanesia sessiliflora (O.Berg) Mattos is a Brazilian native plant species used in a popular medicinal tea for treating gastrointestinal, urinary, and dermatological pathologies. This study evaluated the toxicity of Campomanesia sessiliflora (O.Berg) Mattos via acute and subacute toxicity tests. It also analyzed mutagenic and genotoxic potentials by the micronucleus test, which detects genetic material damage indicating mutagenicity, and the comet assay, which assesses DNA damage levels as a genotoxicity indicator. The plant extract initially originated from the ultrasonic maceration of Campomanesia sessiliflora (O.Berg) Mattos leaves in a hydroethanolic solution. The involved animals were adult Wistar rats. Ten females were available to evaluate acute toxicity and estimate the LD50, receiving a dose of 2000 mg/kg. The subacute toxicity evaluation used 35 females and 35 males divided into seven groups: negative control (saline control – SC), positive control (cyclophosphamide control – CC), 125 mg/kg (125), 250 mg/kg (250), 500 mg/kg (500), 1000 mg/kg (1000), and the satellite group (ST). Genotoxicity and mutagenicity experiments applied bone marrow micronucleus and comet assays. Acute and subacute toxicity tests did not present behavioral, physical, and physiological changes (p≥0.05). Administering the Campomanesia sessiliflora (O.Berg) Mattos extract reduced spleen size in male and female animals, without histopathological changes. However, doses above 500 mg/kg showed significant genotoxic and mutagenic effects in the comet and micronucleus assays compared to the control group. The extract did not exhibit acute or subacute toxicity, but doses higher than 500 mg/kg indicated some level of genotoxicity and mutagenicity.

A toxicological assessment of Ganoderma lucidum and Cordyceps militaris mushroom powders.

Gonoderma lucidum (G. lucidum) and Cordyceps militaris (C. militaris) are among the many mushrooms known for their long history of use in traditional medicine. Wildcrafted sources of mushrooms including G. lucidum and C. militaris can be limited from a scarcity and quality perspective, but solid fermentation processes in cultivation settings can provide an efficient way to deliver whole mushroom preparations of a consistent composition. Despite the historical use of these mushrooms, few published reports have explored their potential subchronic oral toxicity or genotoxicity, either from specific components or whole mushroom preparations. The purpose of this study was to assess the potential for acute toxicity, subchronic toxicity, and genotoxicity of powders produced from G. lucidum mycelial biomass and fruiting body ("Organic Reishi M2-102-02 powder") cultured on oats, and C. militaris mycelial biomass, stroma, and fruiting body ("Organic Cordyceps M2-116-04 powder") cultured on oats. Results of the testing demonstrate that both Organic Reishi M2-102-02 powder and Organic Cordyceps M2-116-04 powder were not acutely toxic, did not exhibit subchronic oral toxicity in rats at doses up to the highest dose tested of 2,000mg/kgbw/day, and did not have genotoxic potential based on in vitro and in vivo genotoxicity assays.

Industrial Genotoxicology Group (IGG): 36th Annual Meeting Report.

The proceedings of the 36th annual meeting of the Industrial Genotoxicology Group (IGG) are shared here. The meeting held at Lhasa Limited, Leeds, UK on 28th November 2023, focussed two aspects; New Approach Methodologies (NAM's), including those for the assessment of non-standard modalities such as gas-vapour assessments and nanomaterials, and addressing the regulatory challenges associated with understanding the genotoxic and carcinogenic potential of N-nitrosamines and N-nitrosamine impurities. New approach methodologies, such as error-corrected sequencing and enhanced Ames tests that may help address these challenges were also discussed.

Immune Modulatory Profile of the Pateamines PatA and Des-Methyl Des-Amino PatA.

Pateamines act as inhibitors of the RNA helicase eIF4A and exhibit antiviral and anticancer properties. Recently, we observed that inhibition of eIF4A by rocaglates affects the immune response. To investigate whether the observed immunomodulatory effects are specific to rocaglates or the inhibition of eIF4A, a comprehensive study was conducted on the influence of pateamines that exhibit the same inhibitory mode of action as rocaglates on various immune cells. The effects of pateamine A (PatA) and des-methyl des-amino pateamine A (DMDA) on the expression of surface markers, release of cytokines, cell proliferation, inflammatory mediators and metabolic activity in primary human monocyte-derived macrophages (MdM), T cells and B cells were assessed. Additionally, safety and bioavailability profiles were determined. DMDA revealed almost no immunomodulatory effects within the tested concentration range of 0.5-5 nM. PatA reduced B cell activation, as shown by reduced immune globulin release and decreased chemokine release from macrophages, while T cell function remained unaffected. Both DMDA and PatA showed low permeability in Caco-2 and Calu-3 cell barrier assays and no mutagenic potential. However, 10 nM PatA exhibited genotoxic potential, as shown by the micronucleus assay. In conclusion, DMDA had a good safety profile but exhibited low permeability, whereas PatA had a poor safety profile and also low permeability. The observed immunomodulatory effects of elF4A inhibitors on B cells appear to be target-specific.

Pentacyclic triterpenoids from the leaves of Cecropia longipes

The genus Cecropia (Urticaceae) comprises 61 tree species primarily found in tropical rainforests from Mexico to South America, including Argentina, Brazil, Paraguay, and Panama. These species are under-researched, with most studies focusing on phenolic derivatives from leaf extracts. Traditionally, Cecropia species are used to treat ailments such as asthma, bronchitis, and diabetes. This study focuses on the underexplored species C. longipes from Panama, aiming to analyze triterpene derivatives in its leaves. Through a series of chromatographic separations and purifications, three pentacyclic triterpenoids were isolated. Using 1D and 2D NMR experiments and HRESI-MS analysis, the following compounds were identified: 19α hydroxyasiatic acid, 1α,3β,23-trihydroxyolean-12-en-28-oic acid, and rosamultic acid. These compounds were isolated for the first time from C. longipes and the genus Cecropia. Genotoxicity tests using S. cerevisiae revealed that two compounds exhibited genotoxic activity at all concentrations. For 19α hydroxyasiatic acid, genotoxic potential was observed at higher concentrations, unrelated to oxidative stress, suggesting other mechanisms.

Effect of CAT gene polymorphism on sensitivity of human lymphocytes to genotoxic effect of organochlorine pesticide in vitro

Introduction. Over recent decades, toxicogenetic studies have focused on the issues of genome instability under the action of genotoxicants, taking into account biomarkers of sensitivity. The question about the genotoxic potential of chlorpyrifos remains open, since both positive and negative effects have been revealed in various tests. The aim of the study is the investigation of sensitivity of donor peripheral blood lymphocytes to chlorpyrifos in vitro and evaluation of the contribution of polymorphism of antioxidant defense system genes (CAT (rs1001179), SOD2 (rs4880)) to the response of human cells to the action of genotoxicant. Materials and methods. The DNA damaging effect of chlorpyrifos was assessed on lymphocytes from fifty two donors using DNA-comet assay with metabolic activation (+S9) and without it (–S9). The study of cytotoxic effects of chlorpyrifos on human lymphocytes was carried out using an automatic fluorescent cell analyzer ADAMII LS. Results. Chlorpyrifos had a pronounced cytotoxic effect on lymphocytes in most donors in the absence of metabolic activation system. With increasing concentration of the pesticide in the medium and time of cultivation, the viability of lymphocytes decreased, and the proportion of cells in late apoptosis and necrosis increased. Positive genotoxic effects were found on the cells of 33 donors (-S9). In the presence of the S9, mild but statistically significant effects were detected only on cells from 2 donors. % DNA values in the comet tail after exposure to the pesticide varied for cells from different donors. In the absence of metabolic activation, a statistically significant increase in the level of DNA damage was found in cells of individuals with genotype AA (homozygote for the minor allele) for the CAT G262A catalase gene (rs1001179), compared with homozygote for the dominant GG allele. Limitations. The genotoxicity of chlorpyryfos was studied in vitro. Conclusion. The results of the study shown cytotoxic and genotoxic effects of chlorpyrifos. The sensitivity of lymphocytes from different donors to the pesticide was found to be significantly different. The association of the level of DNA damage under exposure of chlorpyrifos in vitro with the G262A polymorphism of the catalase gene was found. The research also confirms the possibility of using a model test-system with peripheral blood lymphocytes to assess the potential genetic risk for humans and to study the contribution of gene polymorphism to individual sensitivity to the action of genotoxicants.

Analysis of potential genotoxicity of deicing material in the test for induction of dominant lethal mutations in germ cells of male Drosophila

Introduction. Long-term use of deicing materials (DM) is one of the significant factors causing the active distribution of various chemical compounds that are part of multicomponent deicing mixtures in the environment. In this regard, the expansion of methodological approaches to assessing their biological hazard remains important. Materials and methods. The DM used for research based on a mixture of urea with magnesium and ammonium nitrates. The DM was tested in the form of an aqueous solution and added to the soil to obtain an aqueous extract. The analysis includes test for induced dominant lethal mutations in Drosophila male germ cells. Results. All samples tested significantly reduced the fertility of Drosophila males. The frequencies of early dominant lethal mutations (EDLM) significantly exceeded the levels of the controls, and the effects of the soil extract appeared at the lowest concentration – 5 g/L and of the DM solution – 10 g/L. The trend in the rate of late dominant lethal mutations (LDLM) indicates to the death of sperm or a decrease in mating potency. Limitations. The method of inducing dominant lethal mutations in Drosophila melanogaster and the genotoxic effects assessment of DM in the germ cells of male flies within the study has no restrictions. Conclusion. The conducted test is so far the only one in the field of research into the genetic safety of multicomponent DMs using a method for induced dominant lethal mutations in Drosophila male germ cells. The results prove the high informative rate of the methodological approach which involves analyzing soil extracts to identify and assess a genotoxicity of DM component composition when it enters the soil which can become as a transit layer for migration of DM components and their products transformation into groundwater.

Genotoxicity and safety profile of Eleview®: A submucosal injectable composition for endoscopic mucosal resection and endoscopic submucosal dissection

Background and Objectives: Eleview® submucosal injectable composition with methylene blue (MB), is intended for use in gastrointestinal endoscopic procedures. Given the recognised in vitro mutagenicity of MB, Eleview® mutagenic and genotoxic potentials and its safety profile in acute and subacute toxicity settings were assessed. Methods: Acute and subacute systemic toxicity were tested in rats and dogs, respectively. Ames test and chromosome aberration test in Chinese Hamster V79 cells, were performed. The ratio of polychromatic to normochromatic erythrocytes was assessed in rat bone marrow at the rat MTD. Results: Eleview® oral or intraperitoneal at 20 mL/kg or 50 mL/kg did not induce any acute toxic effects in rats. In dogs, Eleview® (15 mL) did not cause any relevant in-life observations or any histopathological changes in any organs/tissues or injection sites. Ames test demonstrated no concentration-related and reproducible increases in revertant colony numbers. No significant increase of chromosomally aberrant cells was noted in Chinese Hamster cells. Lastly, Eleview® did not elicit significant increase in micronucleated polychromatic erythrocyte frequency. Conclusion: No death or abnormal findings in the acute and subacute studies were observed for Eleview® administration. Eleview® is not genotoxic, nor mutagenic, proving to be a safe medical device to use in clinical practice.