Genotoxicity Profiles Research Articles

Modulating effect of green tea and vitamin C in the management of "Alzheimer's Disease": oxidative stress, cell-based anti-inflammatory and genotoxic profiles.

Modulating effect of green tea and vitamin C in the management of "Alzheimer's Disease": oxidative stress, cell-based anti-inflammatory and genotoxic profiles.

Mutagenic and genotoxic in silico QSAR prediction of dimer impurity of gliflozins; canagliflozin, dapaglifozin, and emphagliflozin and in vitro evaluation by Ames and micronucleus test

Canagliflozin, Dapagliflozin, and Empagliflozin, glucagon-like peptide-1 receptor agonists, are indicated for managing type II diabetes. Although the genotoxicity profiles of these drugs are well-explored, limited information exists regarding the genotoxic potential of their impurities. In this investigation, the dimer impurities of Canagliflozin, Dapagliflozin, and Empagliflozin underwent both in silico and in vitro assessments for mutagenic potential. Tester strains of Salmonella typhimurium and Escherichia coli were subjected to the Ames test, utilizing concentrations of up to 1 µg per plate, with and without the presence of metabolic activation. Evaluation of micronucleus induction in TK6 cells was conducted through a micronucleus test, exploring concentrations up to 500 µg/mL, with or without the presence of exogenous metabolic activation. Under the specific test conditions, the dimer impurities of Canagliflozin, Dapagliflozin, and Empagliflozin showed no evidence of mutagenicity or clastrogenicity, establishing their in vitro classification as nonmutagenic. These findings align with negative in silico predictions from quantitative structure–activity relationship (QSAR) analyses for mutagenicity and genotoxicity of the dimer impurities. Collectively, these studies contribute clinically relevant safety information by confirming that the dimer impurities of Canagliflozin, Dapagliflozin, and Empagliflozin are nonmutagenic and nongenotoxic, emphasizing the consistency between in silico and in vitro data.

Genotoxicity, acute and sub-acute toxicity profiles of methanolic Cordyceps militaris (L.) Fr. extract in Swiss Albino Mice

Ethnopharmacological relevanceCordyceps militaris, a traditional medicinal fungus, parasitizes the intestines of lepidopteron pupae or larvae, predominantly during the winter, and undergoes fruiting in the summer or autumn. Compounds extracted from C. militaris have demonstrated a broad spectrum of pharmacological effects, including antioxidant, anti-tumor, anti-metastatic, anti-inflammatory, antiviral, anti-diabetic, and various others. Aim of the studyHerein, our study aimed at elucidating the acute, sub-acute toxicity, and genotoxicity profiles of C. militaris methanolic extract following oral administration in Swiss albino mice, representing the inaugural comprehensive exploration of the toxicological and safety profiles of C. militaris. Materials and methodsPrior studies have predominantly focused on its biological activities rather than its toxicity. Acute oral toxicity study was conducted at 500, 1000, and 2000 mg/Kg B.W. doses of C. militaris over a 14-day period. For sub-acute toxicity study, three groups of mice were administered 100, 300, and 600 mg/Kg B.W. of C. militaris extract for 28 consecutive days; one group served as a control. Mice were monitored for their body weight and behavioural changes once daily. Hematological, serum biochemical, histopathological, histomorphometric, seminal parameters, and mutagenic investigations were performed post-treatment period. ResultsAcute oral toxicity study at 2000 mg/Kg revealed no signs of toxicity, with an LD50 value surpassing 2000 mg/Kg. No occurrences of mortality observed, and no significant changes were noted in body weight, organ weight, or behaviour. Hematological analysis illustrated a marked upsurge in RBC, Hb, HCT, PLT, MPV, and PCT, alongside minor variations in differential leucocyte count post 28-day treatment. Liver enzyme tests indicated slight elevation in ALP, while renal enzyme tests showed alterations in CRE and BUN levels. Genotoxicity profile and histopathological assessments of the liver, spleen, testis, and ovary manifested no remarkable irregularities, except for mild renal toxicity. Seminal parameters including sperm concentration, motility and testosterone levels demonstrated a noteworthy increase. ConclusionsThe study sheds light on the potential risks and safety considerations associated with C. militaris-based medicinal products. These findings establish a foundation for further investigations and the refinement of dosage optimization in the application of C. militaris, with the aim of mitigating any potential adverse effects.

Urinary mutagenicity and bladder cancer risk in northern New England.

The etiology of bladder cancer among never smokers without occupational or environmental exposure to established urothelial carcinogens remains unclear. Urinary mutagenicity is an integrative measure that reflects recent exposure to genotoxic agents. Here, we investigated its potential association with bladder cancer in rural northern New England. We analyzed 156 bladder cancer cases and 247 cancer-free controls from a large population-based case-control study conducted in Maine, New Hampshire, and Vermont. Overnight urine samples were deconjugated enzymatically and the extracted organics were assessed for mutagenicity using the plate-incorporation Ames assay with the Salmonella frameshift strain YG1041 + S9. Logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) of bladder cancer in relation to having mutagenic versus nonmutagenic urine, adjusted for age, sex, and state, and stratified by smoking status (never, former, and current). We found evidence for an association between having mutagenic urine and increased bladder cancer risk among never smokers (OR = 3.8, 95% CI: 1.3-11.2) but not among former or current smokers. Risk could not be estimated among current smokers because nearly all cases and controls had mutagenic urine. Urinary mutagenicity among never-smoking controls could not be explained by recent exposure to established occupational and environmental mutagenic bladder carcinogens evaluated in our study. Our findings suggest that among never smokers, urinary mutagenicity potentially reflects genotoxic exposure profiles relevant to bladder carcinogenesis. Future studies are needed to replicate our findings and identify compounds and their sources that influence bladder cancer risk.

Both Nitro Groups Are Essential for High Antitubercular Activity of 3,5-Dinitrobenzylsulfanyl Tetrazoles and 1,3,4-Oxadiazoles through the Deazaflavin-Dependent Nitroreductase Activation Pathway.

3,5-Dinitrobenzylsulfanyl tetrazoles and 1,3,4-oxadiazoles, previously identified as having high in vitro activities against both replicating and nonreplicating mycobacteria and favorable cytotoxicity and genotoxicity profiles were investigated. First we demonstrated that these compounds act in a deazaflavin-dependent nitroreduction pathway and thus require a nitro group for their activity. Second, we confirmed the necessity of both nitro groups for antimycobacterial activity through extensive structure-activity relationship studies using 32 structural types of analogues, each in a five-membered series. Only the analogues with shifted nitro groups, namely, 2,5-dinitrobenzylsulfanyl oxadiazoles and tetrazoles, maintained high antimycobacterial activity but in this case mainly as a result of DprE1 inhibition. However, these analogues also showed increased toxicity to the mammalian cell line. Thus, both nitro groups in 3,5-dinitrobenzylsulfanyl-containing antimycobacterial agents remain essential for their high efficacy, and further efforts should be directed at finding ways to address the possible toxicity and solubility issues, for example, by targeted delivery.

Cytotoxic and genotoxic profiles of the pyrethroid insecticide lambda-cyhalothrin and its microformulation Karate® in CHO-K1 cells.

Lambda-cyhalothrin (LCT) and its microformulation Karate® (25 % a.i.) were analysed for its genotoxicity and cytotoxicity on Chinese hamster ovary (CHO-K1) cells. Cytokinesis-block micronucleus cytome (CBMN-cyt) and alkaline single-cell gel electrophoresis (SCGE) bioassays were selected to test genotoxicity. Neutral red uptake (NRU), succinic dehydrogenase activity (MTT) and apoptogenic induction were employed for estimating cytotoxicity. Both compounds were analysed within a concentration range of 0.1-100µg/mL. Only LCT produced a significant augment in the frequency of micronuclei (MNs) when the cultures were exposed to highest concentrations of 10 and 100µg LCT/mL. A noticeable decrease in NDI was observed for cultures treated with LCT at 10 and 100µg/mL. Karate® induced the inhibition of both the proportion of viable cells and succinic dehydrogenase activity and triggered apoptosis 24h of exposition. Whilst an increased GDI in CHO-K1 cells was observed in the treatments with 1-100µg Karate®/mL, the GDI was not modified in the treatments employing LCT at equivalent doses. SCGE showed that Karate® was more prone to induce genotoxic effects than LCT. Only 50µg/mL of Karate® was able to increase apoptosis. Our results demonstrate the genomic instability and cytotoxic effects induced by this pyrethroid insecticide, confirming that LCT exposure can result in a severe drawback for the ecological equilibrium of the environment.

The synthetic dye malachite green found in food induces cytotoxicity and genotoxicity in four different mammalian cell lines from distinct tissuesw.

Malachite green (MG) is a synthetic dye that uses ranges from its application as a tissue dye to that as an antiparasitic in aquaculture. Several studies have reported the presence of this compound in food dyes and in the meat of fish raised in captivity for human consumption, suggesting risks both for the end user and for as those who handle these products because of MG toxic properties described in the literature. Here we evaluated the cytotoxic and genotoxic profiles of MG in four different cell lines (ACP02, L929, MNP01, and MRC-5). Two of these cell lines are stomach cells (normal and cancer lineages) and the potential ingestion of MG makes this a relevant cell type. Cells were treated with MG at concentrations ranging from 0.1μM to 100μM, and tested by MTT assay, a differential apoptosis/necrosis assay (EB/OA), the micronucleus test (MN), and the comet assay. MG exhibits dose-dependent cytotoxicity toward all of the tested cell types; higher concentrations of MG cause cell necrosis, while lower concentrations induce apoptosis. MG has a genotoxic profile increasing the rates of micronuclei, nucleoplasmic bridges, nuclear buds, and DNA fragmentation; L929 and MRC-5 showed more sensibility than ACP02 and MNP01.

In Vitro and In Vivo Anticancer and Genotoxicity Profiles of Green Synthesized and Chemically Synthesized Silver Nanoparticles.

Silver nanoparticles were green synthesized (Ag-PTs) employing the crude extract of Padina tetrastromatica, a marine alga, and their anticancer and safety profile were compared with those of chemically synthesized silver nanoparticles (Ag-NPs) by in vitro and in vivo models. Ag-PT exhibited potent cytotoxicity against B16-F10 (IC50 = 3.29), MCF-7 (IC50 = 4.36), HEPG2 (IC50 =3.89), and HeLa (IC50 = 4.97) cancer cell lines, whereas they exhibited lower toxicity on normal CHO-K1 cells (IC50 = 5.16). The potent anticancer activity of Ag-PTs on cancer cells is due to the liberation of ions from the nanoparticles. Increased ion internalization to the cells promotes reactive oxygen species (ROS) production and ultimately leads to cell death. The in vitro anticancer results and in vivo melanoma tumor regression study showed significant inhibition of melanoma tumor growth due to Ag-PT treatment. Ag-PT is involved in the upregulation of the p53 protein and downregulation of Sox-2 along with the Ki-67 protein. The antitumor effects of Ag-PTs may be due to the additional release of ions at a lower pH of the tumor microenvironment than that of the normal tissue. The results of safety investigations of Ag-PT by studying mitotic chromosome aberrations (CAs), micronucleus (MN) induction, and mitotic index (MI) demonstrated Ag-PT to be less genotoxic compared to Ag-NP. The bioefficacy and toxicology outcomes together demonstrated that the green synthesized silver nanoparticles (Ag-PTs) could be explored to develop a biocompatible, therapeutic agent and a vehicle of drug delivery for various biomedical applications.

In vitro toxicogenomic activity of an MTA/salicylate-based endodontic sealer

This study was designed to investigate whether mineral trioxide aggregate (MTA) Fillapex®, an MTA/salicylate-based endodontic sealer, exerts cytotoxic and toxicogenomic effects on human gingival fibroblasts (HGFs). HGFs were exposed in vitro to MTA Fillapex® at concentrations of 5%, 10%, 20%, and 40% for 24 h. Cytotoxicity, cell survival (5 days), cell cycle kinetics (flow cytometry), genotoxicity (comet assay), and gene (TP53, BAX, and BCL2) expression profiles were evaluated using reverse-transcriptase quantitative polymerase chain reaction. MTA Fillapex® was cytotoxic to HGFs at the two highest concentrations (20% and 40%), and cell survival decreased after 5 days treatment only with 40% concentration. After MTA Fillapex® treatment, there was an increase in the expression of apoptosis-related genes BAX, BCL2, and TP53, but no increase in DNA damage. Cement also induced changes in cell cycle kinetics, apoptosis, and necrosis rates. The data show the ability of MTA Fillapex® endodontic sealer to induce cellular and genetic alterations in HGFs. Our findings suggest that this compound should be used with caution to avoid health-related risks to the buccal tissue.

Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: the special case of molnupiravir

This review considers antiviral nucleoside analog drugs, including ribavirin, favipiravir, and molnupiravir, which induce genome error catastrophe in SARS-CoV or SARS-CoV-2 via lethal mutagenesis as a mode of action. In vitro data indicate that molnupiravir may be 100 times more potent as an antiviral agent than ribavirin or favipiravir. Molnupiravir has recently demonstrated efficacy in a phase 3 clinical trial. Because of its anticipated global use, its relative potency, and the reported in vitro "host" cell mutagenicity of its active principle, β-d-N4-hydroxycytidine, we have reviewed the development of molnupiravir and its genotoxicity safety evaluation, as well as the genotoxicity profiles of three congeners, that is, ribavirin, favipiravir, and 5-(2-chloroethyl)-2'-deoxyuridine. We consider the potential genetic risks of molnupiravir on the basis of all available information and focus on the need for additional human genotoxicity data and follow-up in patients treated with molnupiravir and similar drugs. Such human data are especially relevant for antiviral NAs that have the potential of permanently modifying the genomes of treated patients and/or causing human teratogenicity or embryotoxicity. We conclude that the results of preclinical genotoxicity studies and phase 1 human clinical safety, tolerability, and pharmacokinetics are critical components of drug safety assessments and sentinels of unanticipated adverse health effects. We provide our rationale for performing more thorough genotoxicity testing prior to and within phase 1 clinical trials, including human PIG-A and error corrected next generation sequencing (duplex sequencing) studies in DNA and mitochondrial DNA of patients treated with antiviral NAs that induce genome error catastrophe via lethal mutagenesis.

In vitro cytotoxic and genotoxic effects of Cissus verticillata and Sphagneticola trilobata used for treatment of Diabetes Mellitus in Brazilian folk medicine

Cissus verticillata and Sphagneticola trilobata have been used in Brazilian folk medicine for Diabetes Mellitus treatment, although their pharmacological and toxicological profile has not been clearly established. Thus, the aim of this study was to evaluate the preclinical toxicity of the aqueous extracts of C. verticillata and S. trilobata. The main groups of secondary metabolites were investigated, and the species differed by the presence of coumarins in C. verticillata and by tannins in S. trilobata extracts. The highest contents of phenolic compounds and flavonoids were quantified in C. verticillata infusion with 2.594 ± 0.04 mg equivalents of gallic acid g-1 of extract and 1.301 ± 0.015 mg equivalents of catechin g-1 of extract, respectively. While the extract of S. trilobata showed minimum values of these compounds, with 0.002 ± 0.001 mg equivalents of gallic acid g-1 extract and 0.005 ± 0.0004 mg equivalents of catechin g-1 of extract, respectively. These differences implied the results of in vitro antioxidant activity evaluated using ferric reducing antioxidant power (FRAP), in which the sample of C. verticillata at 5 mg mL-1 showed a value of 122 µM ferrous sulfate equivalents (FSE), while S. trilobata showed 0.93 µM FSE at the same concentration. With respect to cytotoxic assay with murine fibroblast cell line (3T3) only S. trilobata exhibited cytotoxic effects measured by MTT and Sulforhodamine B assays, evidenced by the cell viability value of approximately 16%, in both tests after 24 and 72 hours of exposure of the cells to 5 mg mL-1 of the extract. Comparatively, at 5 mg mL-1 the C. verticillata extract showed cell viability of 142% and 95%, respectively, after 24 hours of cell exposure. On the other hand, both species showed genotoxic profiles evidenced by chromosomal aberrations by Allium cepa bioassay, observed by the higher percentage values of chromosome bridges, chromosome loss, and disturbed anaphase for all concentrations of both extracts than those of the negative control. The results support the characterization of the toxicological profile for both species and create an alert regarding the use of S. trilobata, which should be avoided.

In vitro estrogenic, cytotoxic, and genotoxic profiles of the xenoestrogens 8-prenylnaringenine, genistein and tartrazine

Phytoestrogens have been widely praised for their health-promoting effects, whereas synthetic environmental estrogens are considered a toxicological risk to human health. The aim of this study was therefore to compare in vitro the estrogenic, cytotoxic, and genotoxic profiles of three common estrogen-like endocrine-disrupting chemicals: the phytoestrogens 8-prenylnaringenine (8-PN) and genistein and the synthetic xenoestrogen tartrazine. As assessed by a yeast bioreporter assay and estrogen-dependent proliferative response in human mammary gland adenocarcinoma cell line (MCF-7), 8-PN showed the highest estrogen-like activity of the three compounds, followed by tartrazine and genistein. After 24-h incubation on MCF-7 cells, all three compounds exhibited low cytotoxicity in the lactate dehydrogenase assay and no genotoxicity in the micronucleus assay. These results demonstrate that 8-PN, genistein and tartrazine possess variable estrogenic activity but display little cellular toxicity in short-term tests in vitro. No difference between phytoestrogens and a synthetic xenoestrogen could be established.

In vitro and in vivo genotoxicity assessment of ferric ferrocyanide and potassium-cobalt ferrocyanide

Ferric hexacyanoferrate(II) (Fe4[Fe(CN)6]3), i.e. Prussian blue (PB) has been used for many years to remove from the body the two toxic isotopes of cesium and thallium following irradiation.Recently, potassium cobalt hexacyanoferrate(II) (K2COFe(CN)6), which has shown a better efficacy for decontamination, is also being considered for use to enhance the elimination of cesium isotopes. In view to its preclinical and clinical development, in vitro and in vivo GLP-compliant genotoxicity studies were carried out on this product as well as on PB for comparison. Several tests dissecting the main events leading to genotoxicity, i.e. mutagenicity and chromosomal aberrations, both structural and quantitative were implemented.In vitro, no mutagenic effect was observed in the Ames test but both compounds were positive in the mouse lymphoma assay on TK locus and induced clastogenic effects in the in vitro chromosomal aberrations test on human lymphocytes, either in absence or in presence of metabolic activation.K-Co-ferrocyanide was also assayed in vivo in the mouse bone marrow micronucleus assay and PB was assessed for DNA fragmentation in the rodent Comet assay in both glandular stomach and colon. In the in vivo micronucleus mouse bone marrow, K-Co-ferrocyanide did not display any genotoxic activity up to 2000 mg/kg/d (x2) by oral route. In opposite, PB induced a significant increase in DNA fragmentation both in the glandular stomach and in the colon of rat treated 3 times with intake ranging from 2000 to 500 mg/kg. PB should be considered as an in vivo mutagen as well as Potassium cobalt hexacyanoferrate(II) since the in vitro genotoxicity profiles of both ferrocyanides are quite similar.Their use as cesium/ thallium decontamination agents in human should be assessed following a benefit/risk approach to enable a robust decision-making.

Similar polycyclic aromatic hydrocarbon and genotoxicity profiles of atmospheric particulate matter from cities on three different continents.

The extractable organic material (EOM) from atmospheric total suspended particles (TSP) contains several organic compounds including non-substituted polycyclic aromatic hydrocarbons (PAHs), alkyl-PAHs, and nitro-PAHs. These chemicals seem to be among the key drivers of TSP genotoxicity. We have shown previously that the mutagenic potencies of the EOM from Limeira, Stockholm, and Kyoto, cities with markedly different meteorological conditions and pollution sources are similar. Here we compare the profiles of non-substituted PAHs (27 congeners), alkyl-PAHs (15 congeners), and nitro-PAHs (7 congeners) from the same EOM samples from these cities. We also compared the genotoxicity profiles using comet and micronucleus assays in human bronchial epithelial cells. The profiles of PAHs, as well as the cytotoxic and genotoxic potencies when expressed in EOM, were quite similar among the studied cities. It seems that despite the differences in meteorological conditions and pollution sources of the cities, removal, mixing, and different atmospheric transformation processes may be contributing to the similarity of the PAHs composition and genotoxicity profiles. More studies are required to verify if this would be a general rule applicable to other cities. Although these profiles were similar for all three cities, the EOM concentration in the atmospheres is markedly different. Thus, the population of Limeira (∼10-fold more EOM/m3 than Stockholm and ∼6-fold more than Kyoto) is exposed to higher concentrations of genotoxic pollutants, and Kyoto's population is 1.5-fold more exposed than Stockholm's. Therefore, to reduce the risk of human exposure to TSP genotoxins, the volume of emissions needs to be reduced.

DNA repair and metabolic gene polymorphisms affect genetic damage due to diesel engine exhaust exposure.

Diesel engine exhaust (DEE) is a complex mixture of toxic gases, halogenated aromatic hydrocarbons, alkyl polycyclic aromatic hydrocarbons, polycyclic aromatic hydrocarbons, benzene derivatives, metals and diesel exhaust particles (DEPs) generated from the incomplete combustion of diesel fuel. Many of the compounds in this mixture can cause oxidative damage to DNA and are considered carcinogenic for humans. Further, chronic DEE exposure increases risks of cardiovascular and pulmonary diseases. Despite these pervasive health risks, there is limited and inconsistent information regarding genetic factors conferring susceptibility or resistance to DEE genotoxicity. The present study evaluated the effects of polymorphisms in two base excision repair (BER) genes (OGG1 Ser326Cys and XRCC1 Arg280His), one homologous recombination (HRR) gene (XRCC3 Thr241Met) and two xenobiotic metabolism genes (GSTM1 and GSTT1) on the genotoxicity profiles among 123 mechanics exposed to workplace DEE. Polymorphisms were determined by PCR-RFLP. In comet assay, individuals with the GSTT1 null genotype demonstrated significantly greater % tail DNA in lymphocytes than those with non-null genotype. In contrast, these null individuals exhibited significantly lower frequencies of binucleated (BN) cells and nuclear buds (NBUDs) in buccal cells than non-null individuals. Heterozygous hOGG1 326 individuals (hOGG1 326 Ser/Cys) exhibited higher buccal cell NBUD frequency than hOGG1 326 Ser/Ser individuals. Individuals carrying the XRCC3 241 Met/Met polymorphism also showed significantly higher buccal cell NBUD frequencies than those carrying the XRCC3 241 Thr/Thr polymorphism. We found a high flow of particulate matter with a diameter of < 2.5μm (PM2.5) in the workplace. The most abundant metals in DEPs were iron, copper, silicon and manganese as detected by transmission electron microscopy-energy-dispersive X-ray spectroscopy (TEM-EDX). Scanning electron microscopy (SEM-EDS) revealed particles with diameters smaller than PM2.5, including nanoparticles forming aggregates and agglomerates. Our results demonstrate the genotoxic effects of DEE and the critical influence of genetic susceptibility conferred by DNA repair and metabolic gene polymorphisms that shed light into the understanding of underlying mechanisms.

Development of an integrated assay in human TK6 cells to permit comprehensive genotoxicity analysis in vitro

In vitro genetic toxicology assays are used to assess the genotoxic potential of chemicals or mixtures. They measure chromosome damage (e.g., micronucleus [MN] formation) or gene mutation, and different combinations of data generated from such assays are evaluated in concert in order to identify genotoxic hazards. Mode-of-action (MoA) information is also fundamental to understanding any apparent genotoxic response. In view of the importance of these types of data for full characterization of genotoxic potential, we leveraged relevant endpoints already established in the human TK6 cell line to develop a single integrated assay that measures MN formation, gene mutation (at the thymidine kinase locus), and MoA (DNA damage response biomarkers). Several prototypical direct-acting genotoxins (methyl methanesulfonate, mitomycin C, and 4-nitroquinoline 1-oxide), pro-genotoxins (benzo[a]pyrene and cyclophosphamide monohydrate), and one non-DNA reactive genotoxin (vinblastine sulfate) were assessed in the approach and found to elicit genotoxic profiles that were generally consistent with their MoA. In contrast, the non-genotoxic agents D-mannitol and (2-chloroethyl) trimethyl-ammonium chloride induced negligible effects on all endpoints up to a top concentration of 10 mM. Sodium diclofenac, presumed to be non-genotoxic, provoked an induction in the phosphoserine10-H3-positive cell population within a small window of concentrations (0.157–0.314 mM), as well as increases in γH2AX, nuclear p53, and MN at higher concentrations, although it had no effect on the mutation frequency endpoint. G2M cell cycle arrest was also largely observed in cells that exhibited genotoxicity in the in vitro MN assay. The TK6 cell-based integrated assay represents an in vitro approach that permits comprehensive genotoxicity analysis in a human-relevant test system. Moreover, its vis-à-vis nature may facilitate further comprehension of the range of effects that can manifest in human cells in response to DNA-damaging agents.

Antiaflatoxigenic Thiosemicarbazones as Crop-Protective Agents: A Cytotoxic and Genotoxic Study.

Aflatoxins are secondary fungal metabolites that can contaminate feed and food. They are a cause of growing concern worldwide, because they are potent carcinogenic agents. Thiosemicarbazones are molecules that possess interesting antiaflatoxigenic properties, but in order to use them as crop-protective agents, their cytotoxic and genotoxic profiles must first be assessed. In this paper, a group of thiosemicarbazones and a copper complex are reported as compounds able to antagonize aflatoxin biosynthesis, fungal growth, and sclerotia biogenesis in Aspergillus flavus. The two most interesting thiosemicarbazones found were noncytotoxic on several cell lines (CRL1790, Hs27, HFL1, and U937), and therefore, they were submitted to additional analysis of mutagenicity and genotoxicity on bacteria, plants, and human cells. No mutagenic activity was observed in bacteria, whereas genotoxic activity was revealed by the Alkaline Comet Assay on U937 cells and by the test of chromosomal aberrations in Allium cepa.

Genotoxic Profile and Morphological Variation of the Amanita rubescens Complex: Traditional Knowledge for Safe Consumption in Mexico

Wild mushrooms are important to the nutritional health and economic subsistence of rural populations in Mexico, but inaccurate identification of mushrooms has led to reported cases of poisoning. The aim of this study is to establish genotoxic profiles of mushrooms of the putative Amanita rubescens complex and to link those profiles with morphological attributes that suggest a correct identification of mushrooms, in order to prevent poisoning. Several combinations of amplification products (AMA, PHA, POP1, and POP2 genes) were identified in A. rubescens fungi sold in traditional markets; these genes are related to the presence of toxic polypeptides and its enzymatic regulators. The sequences correspond to a previously reported toxic gene family (MSDIM). All samples with the complete toxic gene profile presented reddish to dark-brown sporomes; this is the only attribute that visually distinguishes samples with toxic potential. Our results suggest that the mushrooms sold in traditional Mexican markets do not correspond to the A. rubescens complex. We conclude that morphological variability allows for identification of edible and inedible mushrooms.

Phytochemical screening and evaluation of neuroprotective, anti-mutagenic and anti-genotoxic effects of Turkish endemic Glaucium acutidentatum

Glaucium species (Papaveraceae) are the medicinal plant that has been used traditionally to have been used for centuries to treat memory impairment. The aim of this study is to investigate the G. acutidentatum methanol and water extracts' phytochemicals and neuroprotective, anti-inflammatory, anti-mutagenic and anti-genotoxic potentials.Chemical composition was screened by using capillary gas chromatography–mass spectrometry (GC–MS). Neuroprotective effect was analyzed on nerve growth factor (NGF) differentiated-PC12 (dPC12) cells from neuroinflammation and neurodegeneration. Also, these extracts were screened for the mutagenic and anti-mutagenic activity by the Salmonella/microsome test system. In addition, genotoxic profiles and anti-genotoxic effects of these extracts were also analyzed by Comet technique.Extracts of G. acutidentatum had strong neuroprotective effects against hydrogen peroxide (H2O2)-induced damage. Also, neurite length was dose-dependently increased in extracts exposed groups compared with the H2O2-treated group. The anti-inflammatory effect of these extracts was parallel to neuroprotective effect. However, these extracts showed strong anti-mutagenicity (72.9–75.0%) and anti-genotoxic properties. Any genotoxic effect was observed of these extracts in lymphocyte cells, analyzed by the Comet assay.These results suggest that methanol and water extracts of G. acutidentatum had neuroprotective and anti-mutagenic effects and contained protective substances that decreasing damage to genetic material.

Bridging a Gap between Cr(VI)-Induced Oxidative Stress and Genotoxicity in Lettuce Organs after a Long-Term Exposure

Chromium (Cr) contamination in arable soils and irrigating water remains a priority, particularly due to the challenges posed to crop production and food safety. Long-term Cr(VI) effects remain less addressed than short-term ones, particularly regarding organ-specific genotoxic profiles. Here we used the crop Lactuca sativa growing in a protected horticultural system and irrigated for 21 days with Cr(VI) (up to 200 mg/L). Besides the oxidative stress, the genotoxicity was evaluated. Shoots and roots showed distinctive oxidative stress status and genotoxic effects, in a dose-dependent manner. While 50 mg/L stimulated antioxidant activities and no major genotoxic effects were found, plants exposed to ≥150 showed an increase of oxidative disorders, together with cytostatic and DNA damage effects, and some mitotic impairment. Leaves showed less oxidative signs at 50 mg/L, while at 150/200 mg/L the antioxidant battery was stimulated. In Cr treated plants, the highest dose increased the DNA damage, reinforcing the idea that DNA breaks were related to mitotic disorders in higher doses. In conclusion, long-term exposure data show a highly responsive root, with a quadratic response meaning higher defenses at lower Cr doses, and higher oxidative and DNA damage and cytostatic effect at a higher dose.