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The toxicity and associated health risks of typical contaminated groundwater were evaluated using bioassays, the SOS/umu test and the micronucleus assay, with a comparison of identified risks based on bioassay and chemical methods. An analysis of 15 water extracts showed that a lifetime cancer risk (LCR) value of 10−6 was recorded for 47% of water extracts. These results indicated that some water extracts did not exhibit toxicity when analysed using one type of bioassay, yet they indicated high toxicity when analysed using another method. Our results also demonstrated that the LCR values from bioassays were generally greater (2.4-foldmax) than those derived from chemical analysis, a finding indicating that risks can be underestimated or false-negative results can be obtained when only chemical-based methods or even just one bioassay is used. This study suggests that the use of multiple bioassays should be considered to be an efficient method and a comprehensive method should be established for risk assessment. Our findings also suggest that groundwater and freshwater in the studied area might pose significant health risks and exhibit toxicity.

Background and Objective: Herniarin is a simple coumarin that is found naturally in some plant species. In this study, we aimed to evaluate the protective effect of herniarin against ionizing radiation-induced genotoxicity and cytotoxicity in human peripheral blood lymphocytes. Methods: Herniarin was added to human lymphocytes before irradiation with a dose of 2 Gy of Xrays. The antagonistic potential of herniarin against radiation was measured by MTT [3-(4,5- dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide] assay, micronucleus assay, flow cytometry, and reactive oxygen species (ROS) level analysis. Results: The maximum survival of lymphocytes against radiation was observed at a concentration of 50 μM of herniarin and a treatment time of 1 h. Pretreatment with 50 μM herniarin significantly decreased the micronuclei frequency, the percentage of apoptotic lymphocytes, and the ROS level in irradiated human lymphocytes. Moreover, 50 μM herniarin significantly increased the cytokinesis blocked proliferation index in irradiated lymphocytes. Conclusion: Herniarin could reduce radiation-induced cytotoxicity and genotoxicity in human lymphocytes. To complete the results of this study, it is suggested that in the future, more preclinical studies with larger samples or animal models be performed on herniarin.

The gut commensal Anaerobutyricum soehngenii is an anaerobe that can produce both propionate and butyrate, metabolites that have been shown to have a positive effect on gut and overall health. Murine and human dose finding studies have shown that oral intake of A. soehngenii has a positive influence on peripheral insulin resistance, thereby reducing the risk of type 2 diabetes. A recent human intervention provided support for the mode of action of A. soehngenii as it affected gene expression in the duodenum, stimulated the secretion of GLP-1 and improved insulin sensitivity. For these reasons A. soehngenii has been proposed as a food ingredient. Before introducing this bacterium to the food chain, however, it must be established that oral intake of live A. soehngenii bacteria does not pose any health risk. As part of the safety analysis of A. soehngenii strain CH106, we performed genotoxicity assays to determine its mutagenic potential (bacterial reverse mutation and in vitro mammalian cell micronucleus tests) and a 90-day subchronic toxicity study in rats to determine overall toxicity potential. The results of both genotoxicity studies were negative, showing no genotoxic effects. For the 90-day subchronic toxicity study, no adverse events were registered that could be attributed to the feeding with A. soehngenii strain CH106. Even at the highest dose, which exceeds the expected daily human intake more than 100-fold, no adverse events were observed. These result support the conclusion that the use of A. soehngenii strain CH106 as a food ingredient is safe.

For many centuries human populations have been suffering and trying to fight with disease-bearing mosquitoes. Emerging and reemerging diseases such as Dengue, Zika, and Chikungunya affect billions of people around the world and recently has been appealing to control with chemical pesticides. Malathion (MT) is one of the main pesticides used against mosquitoes, the vectors of these diseases. This study aimed to assess cytotoxicity and mutagenicity of the malathion for the bioindicator Allium cepa L. using a multivariate and integrative approach. Moreover, an appendix table was compiled with all available literature of insecticides assessed by the Allium cepa system to support our discussion. Exposures during 48h to 0.5 mg mL-1 and 1.0 mg mL-1 MT were compared to the negative control (distilled water) and positive control (MMS solution at 10 mg L-1). The presence of chromosomal aberrations, micronuclei frequency, and mitotic index abnormalities was evaluated. Anaphase bridges were the alterations with higher incidence and presented a significantly elevated rate in the concentration of 0.5 mg mL-1, including when compared to the positive control. The integrative discriminant analysis summarizes that MT in assessed concentrations presented effects like the positive control, corroborating its potential of toxicity to DNA. Therefore, it is concluded that MT in its pure composition and in realistic concentrations used, has genotoxic potential in the biological assessment of A. cepa cells. The multivariate integrative analysis was fundamental to show a whole response of all data, providing a global view of the effect of MT on DNA. Resumo Por muitos séculos, as populações humanas sofrem e tentam combater os mosquitos transmissores de doenças. Doenças emergentes e reemergentes como Dengue, Zika e Chikungunya afetam bilhões de pessoas em todo o mundo e, recentemente, vem apelando ao controle com pesticidas químicos. O Malation (MT) é um dos principais pesticidas usados contra mosquitos, vetores dessas doenças. O objetivo deste estudo foi avaliar a citotoxicidade e a mutagenicidade do MT para o bioindicador Allium cepa L. usando uma abordagem multivariada e integrativa. Além disso, uma tabela suplementar foi compilada com toda a literatura disponível de inseticidas avaliada pelo sistema Allium cepa para apoiar nossa discussão. Exposições ao MT durante 48h a 0,5 mg mL-1 e 1,0 mg mL-1 foram comparadas a um controle negativo (água destilada) e um controle positivo (10 mg L-1 de MMS). Foram avaliadas a presença de aberrações cromossômicas, frequência de micronúcleos e anormalidades no índice mitótico. As pontes anafásicas foram as alterações com maior incidência e apresentaram uma taxa significativamente elevada na concentração de 0,5 mg mL-1, inclusive quando comparadas ao controle positivo. A análise discriminante integrativa resume que o MT nas concentrações avaliadas apresentou efeitos semelhantes ao controle positivo, corroborando seu potencial de toxicidade para o DNA. Portanto, conclui-se que o MT, em sua composição pura e nas concentrações realistas utilizadas, possui potencial genotóxico na avaliação biológica de células de A. cepa. A análise integrativa multivariada foi fundamental para mostrar uma resposta completa de todos os dados, fornecendo uma visão global do efeito da MT no DNA.

H2 receptor antagonists are the medication given for treating stomach ulcers, but lately, reports have shown their role in healing several malignant ulcers. The present work entails the interaction of H2 blocker nizatidine with calf thymus (ct)-DNA for determining the binding mode and energetics of the interaction. Multi-spectroscopic, calorimetric, viscometric and bioinformatic analysis revealed that nizatidine interacted with ct-DNA via groove-binding mode and is characterised by exothermic reaction. Moreover, assessment of genotoxic potential of nizatidine in vitro was carried out in peripheral human lymphocytes by alkaline comet assay. DNA damage occurred at high concentrations of nizatidine. Genotoxicity of nizatidine was also evaluated in vivo by assessing cytogenetic biomarkers viz. micronuclei formation and chromosomal aberration test. Nizatidine was able to induce micronuclei formation and chromosomal damage at high dose. Additionally, cytotoxic activity of nizatidine was determined in cancer cell lines, namely HeLa and HCT-116 and compared with the normal human cell line HEK-293 employing MTT assay. It was observed that nizatidine was more toxic towards HeLa and HCT-116 than HEK-293. Cell morphology analysis by compound inverted microscopy further strengthens the finding obtained through MTT assay.

Relevance. The consumption of caffeine-containing food in the modern world must necessarily be safe for humans, including should not affect the hereditary material of the body. Objective: to determine the possible effect of caffeine at the cytogenetic level by the micronucleus method on erythrocytes. Materials and Methods. The objects for the study were non-linear mice, which were divided into 6 groups - one control group and 5 experimental groups. The first experimental group and the second in the experiment received caffeine in doses of 40 mg/kg and 100 mg/kg.The control group received saline. Caffeine was administered orally. The mutagen (dioxidine) was injected intraperitoneally. On the 5th day of the experimental study, we performed blood sampling for cytogenetic analysis. Results and Discussion. Our study of the caffeine preparation made it possible to determine the following patterns. Firstly, when administered within 5 days, caffeine at a dose of 40 and 100 mg/kg did not cause an increase in the number of micronuclei in erythrocytes in mice. Secondly, the combined use of caffeine (both at a dose of 40mg/kgand at a dose of 100 mg / kg) and dioxidine significantly increased the level of micronuclei in comparison with the control group. Thirdly, caffeine at a dose of 40mg/kgdid not increase the mutagenic activity of dioxidine, but a dose of caffeine of 100mg/kgwhen combined with a mutagen led to a significant increase in the level of cytogenetic damage. Conclusion. According to our data, caffeine in the experimental study was not a mutagen, but at a dose of 100 mg/kg it represented a comutagenic effect.

In order to evaluate the utility of the 3D reconstructed skin micronucleus assay (3DRSMN) to assess clastogenic/aneugenic potential of the fragrance chemicals, a set of 22 fragrance materials were evaluated in 3DRSMN assay. These materials evaluated were also evaluated in an in vitro as well as in vivo micronucleus assay, conducted as per Organisation for Economic Co-operation and Development guidelines. The results of the RSMN assay were in 100% agreement with the in vivo micronucleus assay results. From this dataset, 18 materials were positive in an in vitro micronucleus assay but were negative in an in vivo micronucleus assay. All these 18 materials were also concluded to be negative in 3DRSMN assay, stressing the importance of the assay to help minimize misleading positive outcomes from the in vitro assay. Since the highest exposure for fragrances is through the dermal route, the RSMN assay fits the applicability domain for testing. Thus, RSMN assay is an important alternative to animal testing for characterization of the genotoxicity potential of fragrance materials.

For genotoxicity study simultaneous phytotoxicity and mutagenicity assay with Vicia sativa L. var. Klára was used. For phytotoxicity the following rank orders of growth inhibition can be arranged: for roots: Ni(II) > Cr(VI) > Cr(III); for shoots: Ni(II) > Cr(VI) ≥ Cr (III). For mutagenicity assay root tips of V. sativa were used and chromosome aberrations were determined at least in 500-anatelophases. All tested metals exerted in V. sativa a significant increase of chromosomal aberration rate in applied concentrations. Maximum of aberrations invoked Cr(VI) and the rank order of aberrations fall was: Cr(VI) > Ni(II) > Cr(III). Genotoxic effects of metals were determined by analysis of micronuclei frequency in the pollen tetrads of Tradescantia plants. None of tested metal significantly stimulated micronuclei frequency and genotoxic effect was decreased in order: Cr(VI) ≥ Ni(II) > Cr(III).

Obese subjects have a high baseline of genotoxic stress, but the underlying mechanism is poorly understood. Given that obesity is associated with high bile acids (BA) and low folate, we aimed to determine the interactive effect of folate deficient or supplementation to the genotoxicity and cytotoxicity of BA in human colon and liver cells. NCM460 and L-02 cells were cultured in folate-deficient (22.6 nM) and replete (2260 nM) Roswell Park Memorial Institute (RPMI)-1640 medium with or without 50 μM deoxycholic acid (DCA) or lithocholic acid (LCA) for 7 days. Moreover, these cells were cultured in folate supplemented (5.65, 11.3 and 22.6 μM) and standard (2.26 μM) medium with 200 μM DCA or LCA for 7 days. Genotoxicity and cytotoxicity were measured using the cytokinesis-block micronucleus cytome assay. Our results showed that under folate-replete condition, 50 μM DCA or LCA significantly increased the rate of micronuclei (MN) in NCM460 and L-02 cells. Significantly, the MN-inducing effect of 50 μM DCA or LCA was further enhanced by folate deficiency. Interestingly, folate supplementation exerted a dose-dependent manner to significantly decrease the rates of MN, nucleoplasmic bridges, nuclear buds, apoptosis, and necrosis induced by 200 μM DCA or LCA in NCM460 and L-02 cells. In conclusion, the genotoxicity of moderate BA (50 μM) was exacerbated by folate deficiency and folate supplementation could efficiently protect cells against the genotoxicity and cytotoxicity of high BA (200 μM).

Introduction: Oral cytopathology is able to detect incipient cellular alterations, but it is not routinely applied to this purpose. We aimed to establish a model to screen individuals with no oral lesion exposed to smoking/alcohol, by means of the nuclear area, cell proliferation rate, and analysis of genetic damage. Methods: In this cross-sectional pilot study, 90 patients were allocated into 3 groups: oral cancer group (patients with oral squamous cell carcinoma), tobacco/alcohol group (patients without oral lesions and exposed to these risk factors), and control group (individuals with no lesion and not exposed to tobacco and alcohol). The cytological smears performed in these individuals were stained with Papanicolaou, a silver-staining and a Feulgen reaction. The nuclei of cells were measured, and AgNORs/nucleus and micronuclei (MN) were quantified. The cutoff values were stipulated evaluating the healthy mucosa (control group) and the cancerization field mucosa (oral cancer group). Results: Cutoff values for the screening of individuals exposed to carcinogens were ≥8% of nuclei larger than 100 μm2, ≥3.38 AgNOR/nucleus, and ≥3 MN per 1,000 cells. Conclusions: Nuclear area measurement and AgNORs/nucleus and MN quantification identified the incipient phase of oral carcinogenesis. A screening model for individuals without oral lesion exposed to smoking/alcohol was proposed.

Background. Belonging to the family of Combretaceae, the roots of Anogeissus leiocarpus are traditionally used to treat diabetes, wounds, infections, pain, and gastrointestinal diseases. To our knowledge, no genotoxicity assessment of the plant was reported. Hence, this study was designed to evaluate the potential genotoxic and protective effects of extract of Anogeissus leiocarpus roots using the micronucleus test on mice bone marrow cells in vivo. Methods. Three different concentrations (250, 500, and 1000 mg·kg−1) of hydroalcoholic extract of roots of A. leiocarpus were administered daily for 7 days per os to mice, and the genotoxicity was induced by the administration ip of cyclophosphamide. Genotoxicity and cytotoxicity were evaluated by counting, respectively, the number of micronucleated polychromatic erythrocytes and polychromatic erythrocytes to total erythrocytes in the bone marrow of mice. Results. The administration of A. leiocarpus did neither increase the ratio of the polychromatic erythrocyte (PCE) nor the frequency of micronucleated PCE (MNPCE) significantly in the bone marrow cells of the mice, compared to the vehicle control animals. However, a significant increase in the incidence of MNPCE in the bone marrow cell of the cyclophosphamide-treated mice was found. Moreover, in the groups treated with the total extract of A. leiocarpus at different doses plus cyclophosphamide, there was a significant decrease p < 0.0001 in MNPCEs compared to the positive controls, in a dose-dependent manner. Conclusion. This first finding reports that the extract of A. leiocarpus was neither genotoxic nor cytotoxic. However, it shows a protective effect against the genotoxicity and cytotoxicity induced by cyclophosphamide.

Genotoxicity is described as the property of the agent to cause changes in the genetic material leading to damage in the genetic information, such agents are called as genotoxins. This property is much seen in drugs that are used in the treatment of cancer. Cyclophosphamide is an anticancer drug that lead to gene toxicity through formation of its metabolites and generation of reactive oxygen species and free radicals that damage the genetic material. The main objectives of this research is to evaluate the effect of Momordica cymbalaria (10mg/kg and 50mg/ kg) on cyclophosphamide induced genotoxicity and also to study the genotoxic effect of Momordica cymbalaria (50mg/kg) without Cyclophosphamide treatment. The dose selection was made based on previous acute toxicity report. Animals were treated with Momordica cymbalaria and bone marrow cells were been isolated to observe the effect of drugs on the chromosomes and cellular division through chromosomal aberration assay and micronuclei assay respectively. Effect of drugs on the anti-oxidant enzymes such as glutathione and cellular lipid peroxidation was studied using the liver homogenate. The test drug Momordica cymbalaria showed significant genoprotective effect in dose dependent manner against the chromosomal aberrations and micronuclei formation induced by Cyclophosphamide. And also there was significant inhibition of lipid peroxidation and rise in GSH levels indicating the anti-oxidant property of the test drugs. The drugs Momordica cymbalaria has significant gene protecting effect in cells from Cyclophosphamide induced genotoxicity

The present study explored the effects of combination of Tinospora cordifolia and Arabinogalactan on surface membrane dynamics and programmed cell deaths in rat model of lung cancer. The rats were divided into different groups namely normal control, benzo(a)pyrene (BP) treated, BP + Tinospora cordifolia (TC)-treated, BP + Arabinogalactan (A)-treated and BP + TC + A-treated groups. Significant changes were observed in the membrane dynamics of rats treated with BP. The carcinogen treatment demonstrated a marked decrease in membrane microviscosity. Also, excimer/monomer ratio and fluidity parameters of BP treated rats showed significant rise. On the other hand, combination of Tinospora cordifolia and Arabinogalactan improvised surface membrane dynamics. Moreover, micronuclei formation along with protein expression of bcl-2 showed significant increase in the lungs of BP treated rats. The combined treatment of Tinospora cordifolia and Arabinogalactan moderated the micronuclei formation in BP treated rats. Also, the combined treatment regulated the protein expressions of bcl-2 in BP-treated rats. As a result, marked improvement was noticed in apoptosis of BP treated cells treated with combination treatment. This study concludes that the Tinospora cordifolia and Arabinogalactan in combination improve the surface membrane dynamics and apoptosis in BP-treated rats.

According to the literature genotoxic properties of about a half of hypoglycemic drugs have not been investigated in accordance with the recommended methodology, and studies of the mutagen-modifying activity of antidiabetic drugs are sporadic. Based on the available published data, it is impossible to conclude about either presence or absence of genotoxic / antigenotoxic potential of antidiabetic drugs. There is evidence of the antimutagenic activity of metformin; in relation to other drugs, studies of mutagen-modifying activity have not been carried out or are represented only by a few articles. Further study of the genotoxic properties of hypoglycemic drugs is required in accordance with modern approaches and requirements, as well as an assessment of their mutagen-modifying activity.

Advanced glycation end products (AGEs) are formed via non-enzymatic reactions between amino groups of proteins and the carbonyl groups of reducing sugars. Previous studies have shown that highly glycated albumin prepared using a glucose-bovine serum albumin (Glu-BSA) model system incubated at 60°C for 6 weeks induces genotoxicity in WIL2-NS cells at 9 days of exposure measured by the cytokinesis-block micronucleus cytome (CBMNcyt) assay. However, this AGE model system is not physiologically relevant as normal body temperature is 37°C and the degree of glycation may exceed the extent of albumin modification in vivo. We hypothesised that the incubation temperature and purification method used in these studies may cause changes to the chemical profile of the glycated albumin and may influence the extent of genotoxicity observed at 3, 6 and 9 days of exposure. We prepared AGEs generated using Glu-BSA model systems incubated at 60°C or 37°C purified using trichloroacetic acid (TCA) precipitation or ultrafiltration (UF) and compared their chemical profile (glycation, oxidation, and aggregation) and genotoxicity in WIL2-NS cells using the CBMNcyt assay after 3, 6 and 9 days of exposure. The number of micronuclei (MNi) was significantly higher for cells treated with Glu-BSA incubated at 60°C and purified via TCA (12 ± 1 MNi/1000 binucleated cells) compared to Glu-BSA incubated at 37°C and purified using UF (6 ± 1 MNi/1000 binucleated cells) after 9 days (P < 0.0001). The increase in genotoxicity observed could be explained by a higher level of protein glycation, oxidation, and aggregation of the Glu-BSA model system incubated at 60°C relative to 37°C. This study highlighted that the incubation temperature, purification method and cell exposure time are important variables to consider when generating AGEs in vitro and will enable future studies to better reflect in vivo situations of albumin glycation.

Aim and objective To define the genotoxic potential of tobacco and alcohol in the oral mucosa through a micronuclei (MN) test. Materials and methods Samples of exfoliative cells from oral mucosa were collected using superficial scraping of the right- and left-cheek mucosa of 83 patients divided into four groups, namely: (G1) 24 individuals abstaining from tobacco and alcoholic beverages; (G2) 23 individuals who smoke and abstain from alcoholic beverages; (G3) 24 smokers and alcoholics; and (G4) 12 individuals who consume alcohol and abstain from tobacco. The samples were stained with Giemsa-Wright, and the frequencies of MN, binucleated cells, and metanuclear changes were recorded in the samples of each group (1,000 cells per patient). Results Analysis of variance (ANOVA) showed a difference between groups for changes concerning karyorrhexis (p = 0), pycnosis (p = 0.002), karyolysis (p = 0.003), and binucleated cells (p = 0.046). As for the total number of changes, G3, G2, and G4, respectively, were significantly higher than G1. Conclusion It is suggested that the influence of smoking and drinking on exfoliating cells of oral mucosa may cause metanuclear changes due to genetic changes that these products cause, and the MN test is effective in detecting and monitoring such changes. Clinical significance MN test may work for constantly monitoring the oral mucosa of smokers and/or alcoholic patients, so that early cell changes may be diagnosed, preventing the genesis of oral cancer.

Introduction. Combination antiretroviral therapy is currently the main component of treatment for human immunodeficiency virus (HIV) infected patients. At the same time, the high mutational potential of the virus and the frequency of side effects of existing drugs dictate the need for the development and preclinical study of new, more effective and safer compounds. The aim of the study is to evaluate the specific types of toxicity of a new non-nucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RNA-dependent DNA revertase) (NNRTI) based on the substance 1-[2-(2-benzoylphenoxy)ethyl]-6-methyluracil, a benzophenone derivative. Material and methods. The study investigated reproductive toxicity, embryotoxicity, immunotoxicity, genotoxic (in micronucleus test in and comet assay) and allergenic properties of the test itemcompound. It was tested on three species of animals in two doses: the estimated therapeutic dose (1 TD) and its tenfold equivalent (10 TD). Taking into account the metabolic coefficients, the doses for rats (Rattus) were 9 and 90 mg/kg, for mice (Mus musculus), 21 and 210 mg/kg, and for guinea pigs (Cavia porcellus), 8 and 80 mg/kg, respectively. Results and discussion. According to the obtained results, a favorable safety profile of the tested compound was established. Negative effects on the immune system, reproductive function, the body of pregnant animals and the fetus were not observed, as well as the compound did not have genotoxic and allergenic properties. Conclusion. These data allows to consider the studied compound as a promising therapeutic candidate for the treatment of HIV-1 infection.

Aim The aim of this review was to evaluate the scientific literature regarding the cytogenetic damage in oral exfoliated cells of adult patients submitted to panoramic X-ray. Materials and methods An extensive search of the literature was conducted on PubMed, Scopus and Web of Science databases for all studies published until April 2021 using combinations of the following keywords: "panoramic X-ray," "DNA damage," "genetic damage", "genotoxicity", "mutagenicity", cytotoxicity", "buccal cells", "oral mucosa", "tongue", "gingiva", "micronucleus assay", according to the PRISMA guidelines. All clinical studies in English language were included in the study. A total of 10 studies were identified. Results As expected, the results regarding the cytogenetic damage induced by panoramic X-ray are conflicting. Some authors have demonstrated that panoramic X-ray induces mutagenesis in oral cells, whereas others did not. After reviewing the 10 studies, two were classified as strong, four were considered moderate, and four were considered weak, according to the quality assessment components of the Effective Public Health Practice Project (EPHPP). Meta-analysis data revealed a negative response related to mutagenicity in oral cells by panoramic X-ray. Conclusion Taken together, this review failed to demonstrate the association between micronucleus frequency and panoramic X-ray.

Corrosion of metal orthodontic appliances caused by professional fluoride products has been recently concerned. Therefore, the objective of this study was to evaluate the cytotoxic and genotoxic effect of these products on buccal mucosal cells from patients wearing fixed orthodontic appliances.A total of 44 patients, aged 12 to 35 years, who began orthodontic treatment with fixed appliances were included in this single-center, prospective, randomized clinical trial. Patients were randomly allocated into 4 parallel groups according to the type of professional fluoride treatment applied after placing the appliances: acidulated phosphate fluoride gel (APF); neutral fluoride gel (NGel); fluoride varnish (FVa); and without fluoride treatment (control). Buccal cells were collected before treatment (T1) and 3 months after appliance placement (T2). The cells were assayed for cell viability and underwent Papanicolaou staining. Cells with micronuclei and degenerative nuclear alterations were scored using a light microscope. Cell metal content was quantified by inductively coupled plasma-mass spectrometry. The data were analyzed with the Kruskal-Wallis test.The intracellular nickel content in the APF group significantly increased (P0.05), whereas that of the control, NGel, and FVa groups did not. The changes in chromium concentration in all groups were not significantly different compared with control. Use of APF resulted in a significantly higher decrease in cell viability and increase in morphologic signs of cell death compared with control (P0.05). The change in frequency of micronucleated cells was not significantly different from that in the control group.Applying APF gel on fixed orthodontic appliances increased the cell metal content and decreased cell viability; however, genotoxic effects were absent. FVa and NGel are suggested as the products of choice to use during orthodontic treatment.

The diversity of natural phytochemicals represents an unlimited source for discovery and development of new drugs. Ochradenus arabicus, (family: Resedaceae) a notable medicinal plant displays a high content of flavonoid glycosides. This study investigates a possible preventative role of zinc nanoparticles biosynthesized by O. arabicus leaf extracts (OAZnO NPs) in limiting genotoxicity and cytotoxicity caused by indole acetic acid (IAA) in laboratory mice. ZnO NPs were synthesized using O. arabicus leaf extracts and characterized with UV–visible spectroscopy, scanning electron microscopy (SEM) and X-Ray diffraction (XRD). The mice were randomly distributed into the following six groups: control, OAZnO NPs treated (10 mg/kg BW), IAA treated (50 mg/kg BW); simultaneous treatment, pre-treatment, and post-treatment. Reactive oxygen species (ROS), DNA damage, chromosome aberration, and apoptosis were analyzed as toxicity endpoints. IAA exposure significantly induced production of ROS, DNA damage, apoptosis, chromosome aberrations, and micronuclei. Pre-, post-, and simultaneous treatment with OAZnO NPs ameliorated the damage caused by IAA exposure. Exposure to OAZnO NPs alone caused no toxicity for any endpoint based on comparison to controls. This study demonstrated that IAA-induced cytotoxic damage in mice could be ameliorated by treatment with OAZnO NPs. These findings require additional verification in mechanistic and in vitro studies.

A validation exercise of the hen’s egg test for micronucleus induction was finalised with a very good predictivity based on the analysis of micronuclei in peripheral erythrocytes of fertilised chicken eggs (Reisinger et al. The hen’s egg test for micronucleus-induction (HET-MN): validation data set. Mutagenesis, this issue). For transparency reasons this complementary publication provides further details on the assay especially as it was the first validation study in the field of genotoxicity testing involving the use of chicken eggs. Thus, the experimental protocol is described in detail and is complemented by a scoring atlas for microscopic analysis in blood cells. In addition, general characteristics of the test system, which is able to mirror the systemic availability of test compounds, are delineated: the test compound passes the egg membrane and is taken up by the blood vessels of the underlying chorioallantoic membrane. Subsequently, it is distributed by the circulating blood, metabolised by the developing liver and the yolk sac membrane and finally excreted into the allantois, a bladder equivalent. In specific, the suitability of the test system for genotoxicity testing is shown by, inter alia, a low background DNA damage in a comprehensive historical control database. In addition, the state-of-the-art statistical method used to evaluate obtained data is delineated. It combines laboratory-specific effect threshold with the Umbrella–Williams test, a statistical model also of interest for other genotoxicity test methods.

The ecotoxic state of technologically modified edaphotopes by waste of refinery was investigated with the Allium -test method. Material for the investigations was samples of edaphotopes which were selected at a depth of 15–20 cm from seven research areas of different locations. The last ones were 10–200 m away in relation to the surface storages of oil sludge and other waste of refinery. It has been detected in Allium- test that edaphotopes of the research areas located at a distance of 10–50 m relative to the storages of waste are toxic. Particularly, their aqueous extracts cause a medium and high level of phyto-, cyto- and genotoxic effects on the growing and proliferative activity of Allium cepa Stuttgarter Riesen variety meristem. Test extracts of edaphotopes in growing Allium -test caused darkening of rootlets and blackening of their tips (contrary to the light rootlets with light tips in control). In addition to it the growing activity of A. сepa bulb roots that were grown on the aqueous extracts of edaphotopes was decreased in 1.71–3.5 times depending on the location and measure of remoteness of the research area from the storage of waste of the refinery. Phytotoxicity of aqueous extracts of those edaphotopes regarding to A. сepa is above average and higher levels, and tolerance of onion rootlets to the test extracts decreases up to 29–52 % comparing to control . The mitotic activity of apical meristem of rootlets also decreased. Particularly, mitotic indexes diminished to 51.05–63.57 % (in control – 82.34 %) and cytotoxicity ones were in the range of 22.8–48.0 % that confirms the medial level of cytotoxicity of the investigated edaphotopes. Ana-telophase method and micronucleus test have shown that the chromosome aberrations frequency and appearance of micronuclei in the cells of the apical meristem of the test object A. cepa is higher in 3.34–5.20 times comparing to control. It indicates the average and the high level of genotoxicity of the investigated edaphotopes. The edaphotopes, which are located at the distance of 100–200 m in relation to the surface storages of waste of refinery have a slight phyto-, cyto- and genotoxic effects which are close to the background level.

Aim: Fermotein is an innovative single-cell protein obtained from fermentation of the filamentous fungus Rhizomucor pusillus. Like other filamentous fungi, a lack of information on this species exists to assess its safety for human consumption. The capability to induce gene mutations or structural and numerical chromosomal aberrations of this fungus and derived products has never been studied before. The objective of the current study was to investigate the genotoxic effects of Fermotein using a bacterial reverse mutation test and an in vitro mammalian cell micronucleus test. Methodology: The bacterial reverse mutation test and in vitro mammalian cell micronucleus test were performed in accordance with GLP and concurrent OECD guidelines. Dose-range finding tests were used to select appropriate doses of Fermotein Dry. The highest doses in the genotoxicity experiments were determined by the solubility of the mycoprotein. Results: The bacterial reverse mutation test and in vitro mammalian cell micronucleus test were performed in accordance with GLP and concurrent OECD guidelines. Dose-range finding tests were used to select appropriate doses of Fermotein Dry. The highest doses in the genotoxicity experiments were determined by the solubility of the mycoprotein. Conclusion: No safety concerns regarding genotoxicity were identified for Fermotein and no further in vivo genotoxicity testing is required. Information from the current study contributes to the body of evidence for a novel food authorisation of Fermotein in the EU and a GRAS notification in the US.

Consequences of waterborne silicon di oxide nanoparticles (SiO2 NPs) on snake headed fish, Channa punctatus were investigated and analyzed for oxidative stress and genotoxicity in a long-term assay. Fish were divided into three groups: Group I (control), Group II and III considered as treated groups. Fish were exposed to 25% and 50% of LC50 value (60 and 120 mg/l of SiO2 NPs) at day 7,15,21,28 and 35. Fish exposed to higher concentrations of SiO2 NPs showed major alterations in oxidative stress markers. Significant alterations were noted in SOD, CAT, GST, GSH, GPx and GR in the gills, liver and kidney of fish of both treated groups. A significant increase of SOD, CAT, GST, GPx and GR in the gill, liver and kidney of fish was observed, whereas GSH showed significant decrease in all treated groups in all tissues. LPO was also estimated in gills, liver and kidney and elevation was noted. By standard genotoxicity test such as micronucleus test and comet assay, genetic damage (cytoplasmic, nuclear and DNA damage) was recorded which indicates significant toxicity of SiO2 NPs at higher concentrations. Significant changes in all parameters studied thus reflected an adverse influence of SiO2 Nps exposure on oxidative stress as well as genotoxicity of the fish. SiO2 Nps toxicity appeared to be dose and duration dependent. The presence of SiO2 Nps leads to an activation of the antioxidant defense system and the occurrence of lipid and genetic damage if antioxidant enzymes were unable to overcome oxidative stress.

The release of contaminants as herbicides, fungicides and insecticides into the environment has been listed as one of the six major contributors to the global decline of reptiles. Although reptiles may face severe risk from contaminants due to their ecology and physiology, they are currently less studied than other vertebrate groups. In the present work, we investigated if and how different types of field treatment (conventional and organic) affected the health status of Italian wall lizard (Podarcis siculus) individuals in central Italy. We chose a multi-biomarker approach that evaluated the biological responses of lizards to the treatment by means of AChE activity in the nervous system, biotransformation enzymes activities and oxidative stress in the liver, micronuclei frequency measured in the erythrocytes, and rate of intestinal parasitic infection. Our findings showed evidence of effects of treatment in conventional areas and between sexes with significant oxidative stress due to hydroxyl radicals, that caused DNA damage. No difference of intestinal parasite infections was found among treatments. Podarcis siculus seems to be a good bioindicator in ecotoxicological studies and potentially in risk assessment of pesticides, although further analyses in laboratory and in the field are needed to achieve more accurate quantification of specific pesticide effects in relation to known exposure history and to understand if other mechanisms were involved in the toxicity and detoxification process of pesticides for this species.

At any moment, the continuous usage of medications can accompanied by DNA damage and the accumulation of such damages can cause serious consequences. Antidepressants are long-term used drugs and the incidence of their genotoxic impacts cannot be excluded. Therefore, this work was designed to investigate the possible genotoxic effects of the commonly used antidepressants (fluoxetine and amitriptyline) in adult male rats. Detection of DNA damage in individual cells was assessed by comet and micronucleus assays in three different cell populations i.e. liver, testis and bone marrow tissues of 24 swiss albino adult male rats. The animals were randomly allocated into three groups of 8 rats each: Group I - rats orally-administered distilled water via gavage tube for four weeks as a negative control. Group II - rats orally-treated with fluoxetine hydrochloride solution (7.2mg/kg/day) via gavage tube for four weeks. Group III - rats orally-treated with amitriptyline hydrochloride solution (27mg/kg/day) via gavage tube for four weeks. The results showed that both drugs (Group II and Group III) induced the same extent of DNA damage, as evidenced by a significantly higher DNA fragmentation in liver and testis tissues with increased frequencies of micronuclei formation in bone marrow tissues as compared with the negative control (Group I). These findings indicates that both Fluoxetine and Amitriptyline have genotoxic potentials and can induce the same extent of cytogenetic damage in rats. Special precautions and medical supervision should be taken in consideration with their uses.

This study aimed at determining in animal model the health effects of in situ exposure to landfill chemicals. We evaluated metal concentrations in tissues and cytogenetic and clinico-biochemical effects in Wistar rats (Rattus norvegicus) exposed in situ at Olusosun landfill in Lagos, Nigeria. Male rats (n = 30/point) were exposed at three different points to ambient air and underground water (via drinking) at the landfill for 4-, 8-, 12-, 16-, 20- and 24-week periods. Rats concurrently sited at a residential area, 17.3 km from the landfill site served as control. There was significantly (p

Micronuclei are small membrane-bounded compartments with a DNA content encapsulated by a nuclear envelope and spatially separated from the primary nucleus. Micronuclei have long been linked to chromosome instability, genome rearrangements, and mutagenesis. They are frequently found in cancers, during senescence, and after genotoxic stress. Compromised integrity of the micronuclear envelope delays or disrupts DNA replication, inhibits DNA repair, and exposes micronuclear DNA directly to cytoplasm. Micronuclei play a central role in tumorigenesis, with micronuclear DNA being a source of complex genome rearrangements (including chromothripsis) and promoting a cyclic GMP–AMP synthase (cGAS)-mediated cellular immune response that may contribute to cancer metastasis. Here, we discuss recent findings on how micronuclei are generated, what the consequences are, and what cellular mechanisms can be applied to protect against micronucleation.

Apoptosis or programmed cell death is a highly regulated process, which eliminates unwanted and damaged cells. Inhibition of apoptosis is a hallmark of cancer cells. BCL2 family proteins are known to play a vital role in the regulation of apoptosis. Overexpression of BCL2, an antiapoptotic protein, provides the advantage of prolonged survival to cancer cells. Over the years, several BCL2 inhibitors have been investigated extensively for their anticancer potential. However, most of them were abolished before clinical use due to their side effects. Previously, we had identified and characterized a novel BCL2 inhibitor, Disarib, with the potential to eliminate tumor cells in a BCL2 specific manner leading to reduction in tumor burden in multiple mouse models. Notably, a head-to-head comparison of Disarib to ABT199, the only FDA approved BCL2 inhibitor revealed that Disarib is as potent as ABT199. Recent studies using mice revealed that Disarib did not invoke significant side effects in mice. In the present study, we have investigated the acute toxicity of Disarib in Wistar rats. The bioavailability studies following exposure of Disarib in Wistar rats revealed its maximum availability in serum at 24 h following oral administration. Acute toxicity analysis revealed that even a dose as high as 2000 mg/kg of Disarib did not cause significant toxicity in rats. There was no significant variation in blood parameters or kidney and liver functions following administration of Disarib. Histological analysis of different tissues from Disarib treated groups revealed standard architecture with no observable cellular damage. Importantly, exposure to Diasrib did not result in genotoxicity as determined by micronucleus assay. Further, solubility assays revealed that besides DMSO, Disarib is also soluble in alcohol. While the high acidic condition can increase the solubility of Disarib, even a lower percentage of alcohol with acidic conditions can improve its solubility. Thus, the toxicological profile in the current study revealed no significant side effects when Disarib was administered orally to rats.

Background: The search for novel metallic chemical compounds with toxicogenic effects has been of great importance for more efficient cancer treatment. Objective: The study evaluated the cytotoxic, genotoxic and mutagenic activity of organoteluran RF07 in the S-180 cell line. Methods: The bioassays used were cell viability with 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, evaluation of apoptosis and necrosis using fluorescence and flow cytometry, cytokinesisblock micronucleus test and comet assay. The compound was tested at 1; 2.5 and 5μM. Results: The results showed the cytotoxicity of RF07 at concentrations of 2.5, 5, 10 and 20μM when compared to the negative control. For genotoxicity tests, RF07 showed effects in all concentrations assessed by increased index and frequencies of damage and mutagenic alterations. The compound was also cytotoxic due to the significant decrease in the nuclear division index, with significant values of apoptosis and necrosis. The results of fluorescence and flow cytometry showed apoptosis as the main type of cell death caused by RF07 at 5μM, which is thought to avoid an aggressive immune response of the organism. Conclusion: In addition to cytotoxic and genotoxic effects, RF07 creates good perspectives for future antitumor formulations.

Among the parabens, methylparaben (MeP) is the most commonly found in personal care products. Due to the continuous use of MeP and low removal efficiency by wastewater treatment plants (WWTPs), it reaches aquatic environments, where it is incorporated by organisms inhabiting these waters. The present study aimed to evaluate the effects of MeP on the zebrafish Danio rerio larvae and adults through toxicity tests and physiological and biochemical biomarkers in order to assess possible harmful effects of MeP. For biomarker measurements, fish were exposed to the environmental concentration of 30 μg/L of MeP and the non-effect concentration (NOEC) estimated for larvae (60 mg/L) and adult (50 mg/L) in toxicity tests. The median lethal concentration (LC50) of MeP was 105.09 mg/L for adults and 211.12 mg/L for larvae. These values unexpectedly indicated that adults were more sensitive to MeP compared to larvae. In adult fish, exposure to 50 mg/L MeP induced a significant decrease in phase 1 biotransformation (ethoxyresorufin O-deethylase activity) and an increase in lipoperoxidation (LPO) in gills, as well as an increase in frequency of micronuclei in erythrocytes of these fish. Biomarkers results were integrated (integrated biomarker response [IBR] index), and it observed lower IBR scores in tissues of fish exposed to MeP, suggesting a suppression of biological responses. In addition, LPO contributed mostly to the IBR score estimated for gills of fish exposed to 50 mg/L MeP. Based on LPO quantity, sublethal exposure of MeP (30 μg/L and 60 mg/L) did not cause toxicity to larvae. Hence, we investigated whether the difference in sensitivity between adults and larvae could be associated with the antimicrobial action of MeP that could affect the intestinal microbiota of adults. We only found an increase in the number of carbon sources consumed by them without effects on diversity and abundance. This outcome can be considered an adaptation to environmental stress, but not a negative effect. However, the LPO and genotoxicity caused by MeP to zebrafish adults call direct attention to the importance of regulating the presence of this compound in the environment and improve cleaning processes adopted by WWTP.

The aim of this study was to evaluate cytogenotoxicity in mammalian cells induced by ingestion of superficial water from SESS. For this purpose, surface water was collected from two points of SESS: Sao Vicente Channel (SVC) and Piacaguera Channel (PIC). Four groups (n = 5) of adult male Wistar (8 weeks old) received for 5 days: (a) filtered tap water (water control), (b) tap water with 2.4% of NaCl (saline control), (c) estuarine water from PIC and (d) estuarine water from SVC. Results demonstrated that Ki67 immunoexpression was higher in hepatocytes exposed to both sampling site, while caspase-3 demonstrated downregulation in rat liver exposed to estuarine water. There was also significant increase in micronuclei frequency in bone marrow cells and hepatocytes, and DNA damage in blood and liver of rats exposed to estuarine water from SVC and PIC. In summary, studies with complex mixtures, such as contaminated estuarine water are important since this work confirmed by experiments using in vivo mammalian cells of rats that SESS water are genotoxic, mutagenic and cytotoxic, denoting concern for environmental health.

Black cohosh extract (BCE) is marketed to women as an alternative to hormone replacement therapy for alleviating menopausal symptoms. Previous studies by the National Toxicology Program revealed that BCE induced micronuclei (MN) and a nonregenerative macrocytic anemia in rats and mice, likely caused by disruption of the folate metabolism pathway. Additional work using TK6 cells showed that BCE induced aneugenicity by destabilizing microtubules. In the present study, BCE-induced MN were confirmed in TK6 and HepG2 cells. We then evaluated BCE-induced DNA damage using the comet assay at multiple time points (0.5–24 h). Following a 0.5-h exposure, BCE induced significant, concentration-dependent increases in %tail DNA in TK6 cells only. Although DNA damage decreased in TK6 cells over time, likely due to repair, small but statistically significant levels of DNA damage were observed after 2 and 4 h exposures to 250 µg/ml BCE. A G1/S arrest in TK6 cells exposed to 125 µg/ml BCE (24 h) was accompanied by apoptosis and increased expression of γH2A.X, p-Chk1, p-Chk2, p53, and p21. Conditioning TK6 cells to physiological levels of folic acid (120 nM) did not increase the sensitivity of cells to BCE-induced DNA damage. BCE did not alter global DNA methylation in TK6 and HepG2 cells cultured in standard medium. Our results suggest that BCE induces acute DNA strand breaks which are quickly repaired in TK6 cells, whereas DNA damage seen at 4 and 24 h may reflect apoptosis. The present study supports that BCE is genotoxic mainly by inducing MN with an aneugenic mode of action.

INTRODUCTION: Immunosuppressant drugs are increasingly being used in the reproductive years. Theoretically, such medications could affect fetal health either through changes in the sperm DNA or through fetal exposure caused by a presence in the seminal fluid. This systematic overview summarizes existing literature on the spermatotoxic and genotoxic potentials of methotrexate (MTX), a drug widely used to treat rheumatic and dermatologic diseases, and mycophenolate mofetil (MMF), which alone or supplemented with ganciclovir (GCV) may be crucial for the survival of organ transplants.MATERIAL AND METHODS: The systematic overview was performed in accordance with the PRISMA guidelines: A systematic literature search of the MEDLINE and Embase databases was done using a combination of relevant terms to search for studies on spermatotoxic or genotoxic changes related to treatment with MTX, GCV or MMF. The search was restricted to English language literature, and to in vivo animal studies (mammalian species) and clinical human studies.RESULTS: A total of 102 studies were identified, hereof 25 human and 77 animal studies. For MTX, human studies of immunosuppressive dosages show transient effect on sperm quality parameters, which return to reference values within 3 months. No human studies have investigated the sperm DNA damaging effect of MTX, but in other organs the genotoxic effects of immunosuppressive doses of MTX are fluctuating. In animals, immunosuppressive and cytotoxic doses of MTX adversely affect sperm quality parameters and show widespread genotoxic damages in various organs. Cytotoxic doses transiently change the DNA material in all cell stages of spermatogenesis in rodents. For GCV and MMF, data are limited and the results are indeterminate, for which reason spermatotoxic and genotoxic potentials cannot be excluded.CONCLUSIONS: Data from human and animal studies indicate transient spermatotoxic and genotoxic potentials of immunosuppressive and cytotoxic doses of MTX. There are a limited number of studies investigating GCV and MMF.

Made available in DSpace on 2021-06-25T11:11:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-01 Objective: The aim of this study was to investigate cytogenetic and cytotoxic damage through the evaluation of micronuclei (MN) and metanuclear anomalies in the oral mucosa of electronic cigarette (e-cig) users. Study Design: The patients were recruited into 4 groups: e-cig users, smokers, former smokers, and nonsmokers (control). The samples were collected by means of exfoliative cytology of the lateral region of the tongue and the floor of the mouth. The smears obtained were fixed and stained by the Feulgen method for investigation of MN and metanuclear anomalies. Results: A significant difference was observed for MN frequency only between the smoker and control groups. As for metanuclear anomalies, significant differences were observed: karyolysis between: smokers and control, e-cig and control, as well as former smokers; karyorrhexis: between smoker and control; binucleation: between e-cig and former smoker, as well as control; broken eggs: between e-cig and all other groups; nuclear bud: between e-cig and former smokers, as well as control. Conclusions: E-cig and alcohol users presented genotoxicity and cytotoxicity in the oral mucosa cells. The use of e-cigs and alcohol by former smokers can cause more damage to the cells of the oral mucosa compared to those who have not used e-cigs. Department of Biosciences and Diagnosis Institute of Science and Technology São Paulo State University (Unesp) School of Dentistry Universidade Mogi das Cruzes School of Medicine Universidade Anhembi Morumbi Outpatient Smoking Treatment Program of the Heart Institute (Incor) Faculty of Medicine University of São Paulo (FMUSP) Department of Biosciences and Diagnosis Institute of Science and Technology São Paulo State University (Unesp)

Objective: Nanotechnology is an emerging technology which has wide applications in many fields. Prime concern of research in nanotechnology is the synthesis of nano-material with the controlled size and shape. Recently, biosynthesis of metallic nano-particles has gained popularity owing to its eco-friendliness. The increasing use of Copper nanoparticles (CuNPs) in medicine and industry demands an understanding of their potential toxicities. Methods: Genotoxicity of Copper nanoparticles was assessed using the in vitro micronucleus assay which is standard genotoxicity assay. In this study, Copper nanoparticle was tested in the absence and presence of the metabolic activation (2% v/v S9 mix). Human peripheral blood lymphocyte cultures were exposed to Copper nanoparticle, at 5 dose-levels between 0.125 to 2 µL/mL of culture medium in absence and presence of the metabolic activation system. Results: Required level of cytotoxicity (55 ± 5% reduction in replicative index, i.e., cytostasis) was observed in absence of the metabolic activation at the test concentration of 2 µL/mL. Therefore dose levels selected for scoring of binucleated cells containing micronuclei were: 0.5, 1, and 2 µL/mL. From the obtained data of MNBN cells (Binucleated cells with micronuclei) for all three selected test concentration was found in the range of negative and vehicle control. Conclusion: Our results concluded that, Copper nanoparticle did not induce statistically significant or biologically relevant increase in number of binucleated cells with micronuclei in absence and presence of the metabolic activation.

Leptolyngbya sp. KIOST-1 (LK1) is a newly isolated cyanobacterium that shows no obvious cytotoxicity and contains high protein content for both human and animal diets. However, only limited information is available on its toxic effects. The purpose of this study was to validate the safety of LK1 powder. Following Organisation for Economic Co-operation and Development (OECD) guidelines, a single-dose oral toxicity test in Sprague Dawley rats was performed. Genotoxicity was assessed using a bacterial reverse mutation test with Salmonella typhimurium (strains TA98, TA100, TA1535, and TA1537) and Escherichia coli WP2 uvrA, an in vitro mammalian chromosome aberration test using Chinese hamster lung cells, and an in vivo mammalian erythrocyte micronucleus test using Hsd:ICR (CD-1) SPF mouse bone marrow. After LK1 administration (2,500 mg/kg), there were no LK1-related body weight changes or necropsy findings. The reverse mutation test showed no increased reverse mutation upon exposure to 5,000 μg/plate of the LK1 powder, the maximum tested amount. The chromosome aberration test and micronucleus assay demonstrated no chromosomal abnormalities and genotoxicity, respectively, in the presence of the LK1 powder. The absence of physiological findings and genetic abnormalities suggests that LK1 powder is appropriate as a candidate biomass to be used as a safe food ingredient.

The cyanotoxin cylindrospermopsin (CYN) is the second biggest cause of poisoning worldwide, both in humans and animals. Although CYN primarily affects the aquatic environments and can be absorbed in fishes by multiple routes, data reporting its toxicity and mechanism of action are still scarce in this group. Using P. reticulata as model species, it was evaluated whether CYN promotes mutagenic and genotoxic effects in different fish target tissues. Adult females were exposed in a static way to 0 (control), 0.5, 1.0, and 1.5 μg L-1 of pure CYN for 24 and 96 hours. For the first time, DNA damage was detected in fish brain after CYN exposition. In brain cells, a concentration-response DNA damage was observed for both exposure times, suggesting a direct or indirect action of CYN in neurotoxicity. For the liver cells, 96 hours caused an increase in DNA damage, as well the highest percentage of DNA in the tail was reached when used 1.5 μg L-1 of CYN. In peripheral blood cells, an increase in DNA damage was observed for all tested concentrations after 96 hours. In erythrocytes, micronuclei frequency was higher at 1.5 μg L-1 treatment while the erythrocyte nuclear abnormalities (ENA) frequency was significantly higher even at the lowest CYN concentration. Such data demonstrated that acute exposition to CYN promotes genotoxicity in the brain, liver, and blood cells of P. reticulata, as well mutagenicity in erythrocytes. It rises an alert regarding to the toxic effects of CYN for aquatic organisms as well as for human health.

Most women with breast cancer can become pregnant and give birth while undergoing radiation therapy and breastfeeding is generally not contraindicated. The induction of long-lived reactive species in proteins, such as casein by X-ray radiation and DNA damage to unexposed organisms, has been shown when ingesting irradiated cheese. To determine whether exposing lactating rats to X-rays increases the number of micronucleated erythrocytes (MNEs) in peripheral blood of their unexposed or breastfeeding rat pups, 15 female Wistar rats were divided into three groups: Negative control; Experimental group exposed to X-rays, and group exposed to X-rays plus vitamin C. The mothers of groups 2 and 3 were irradiated for three consecutive days after giving birth, returning them to their respective cages each time to continue lactation. A blood sample was taken from the mothers and pups at 0, 24, and 48 hr. Blood smears were stained with acridine orange to analyze MNEs. In mother rats, the frequency of micronucleated polychromatic erythrocytes (MNPCEs) increased significantly at 24 and 48 hr in both study groups exposed to radiation. Likewise, in rat pups the MNPCE and MNE frequencies increased in both groups with radiation and radiation plus vitamin C at 24 and 48 hr, and a protection from vitamin C was observed. In conclusion, the genotoxic damage produced in rat pups that were lactated by mothers irradiated with X-rays is possibly due to the effect of long-lived reactive species that were formed in the breast milk of female Wistar rats during the irradiation process.

Fipronil (FPN) is a wide-ranging effective N-phenylpyrazole insecticide that is commonly used in agriculture and public health for a long time but until now no adequate data available concerning its side effect. The present study was to evaluate the oxidative stress, cytotoxicity, and mutagenic effect of FPN subchronic exposure. Twenty male Albino rats (120g±10%) were randomly assigned into four groups each has five animals, a control group, two FPN treated groups with doses of 3.9, and 2.3 mg kg-1 b.w. per day for 90 days and the fourth group is a positive control group. Superoxide Dismutase (SOD), Catalase (CAT), and Malondialdehyde level (MDA) were used as oxidative stress biomarkers. The cytotoxicity was estimated by micronucleus assay, while the mutagenic effect was studied on the P53 tumor suppressor gene using the single-strand conformation polymorphism (SSCP) technique. The results showed that SOD significantly decreased in the high and low doses treatments and insignificant changes in CAT compared to control. MDA was significantly elevated in the high dose group and remained insignificant in the low dose. The high dose of FPN was showed an increased number of micronuclei in the Normochromatic Erythrocytes (NCE) in the bone marrow. PCR-SSCP analysis by acrylamide gel didn’t show mutations in the P53 gene. This study demonstrated that FPN induces oxidative stress and micronuclei but did not show alternation of the P53 gene. The study indicated the relative safeness of fipronil to be used in the public health field with taking all use precautions.

Tobacco use may initiate the process of oral carcinogenesis with clinically undetectable changes. Smoking cessation may prevent its progression. The objective of this study was to evaluate the association between DNA ploidy and micronucleus (MN) frequency in chronic smokers. Three groups were evaluated: Smoker Group, Former Smoker Group and Control Group. Exfoliative cytology was performed on the lateral border of the tongue and mouth floor. MN and DNA ploidy analyses were performed, as well as the correlation between the variables. The data showed a difference between the groups for the total MN (p = 0.0227), and the Smoker group had the highest mean (4.22 ± 4.12). The three groups did not differ statistically from each other on ploidy evaluation (p-value > 0.05). There was also an association between aneuploidy and increased MN frequency in the Former Smoker group (p = 0.0036). In conclusion, these results point out that there is a relationship between the frequency of MN and aneuploidy in former smokers. Moreover, smoking cessation, even for a short period of time, may promote the decrease of MN frequency caused by tobacco use.

The use of irrigation water containing cyanobacterial toxins can cause significant impacts in agricultural and consequently environmental health. The purpose of this study is to evaluate the effects of cyanotoxins (microcystin-LR and saxitoxin) on germination, growth and micronuclei formation in lettuce (Lettuce sativa) and coriander (Coriandrum sativum). Seeds of lettuce and coriander were exposed during 7-9 days to environmentally relevant concentrations of microcystin-LR (MC-LR1= 0.4 µg/L; MC-LR2= 1.0 µg/L; MC-LR3= 5.0 µg/L) and saxitoxin (SX1= 0.02 µg/L; SX2= 0.1 µg/L; SX3= 0.4 µg/L). In germination test, differential responses were observed being lettuce the most affected in the presence of saxitoxin, and coriander to microcystin-LR treatments. Cyanotoxins inhibit seedlings development to both plants species and promote formation of micronuclei in root cells. Cyanotoxins inhibit seed germination, growth and cause DNA damages, but the intensity depends on both the nature of the toxin and plant species. Key words: Cyanobacterial toxin, microcystin-LR, saxitoxin, micronuclei, lettuce, coriander.

The present study aimed to evaluate the effect of the manool diterpene on genomic integrity. For this purpose, we evaluated the influence of manool on genotoxicity induced by mutagens with different mechanisms of action, as well as on colon carcinogenesis. The results showed that manool (0.5 and 1.0 µg/ml) significantly reduced the frequency of micronuclei induced by doxorubicin (DXR) and hydrogen peroxide in V79 cells but did not influence genotoxicity induced by etoposide. Mice receiving manool (1.25 mg/kg) exhibited a significant reduction (79.5%) in DXR-induced chromosomal damage. The higher doses of manool (5.0 and 20 mg/kg) did not influence the genotoxicity induced by DXR. The anticarcinogenic effect of manool (0.3125, 1.25 and 5.0 mg/kg) was also observed against preneoplastic lesions chemically induced in rat colon. A gradual increase in manool doses did not cause a proportional reduction of preneoplastic lesions, thus demonstrating the absence of a dose–response relationship. The analysis of serum biochemical indicators revealed the absence of hepatotoxicity and nephrotoxicity of treatments. To explore the chemopreventive mechanisms of manool via anti-inflammatory pathways, we evaluated its effect on nitric oxide (NO) production and on the expression of the NF-kB gene. At the highest concentration tested (4 μg/ml), manool significantly increased NO production when compared to the negative control. On the other hand, in the prophylactic treatment model, manool (0.5 and 1.0 μg/ml) was able to significantly reduce NO levels produced by macrophages stimulated with lipopolysaccharide. Analysis of NF-kB in hepatic and renal tissues of mice treated with manool and DXR revealed that the mutagen was unable to stimulate expression of the gene. In conclusion, manool possesses antigenotoxic and anticarcinogenic effects and its anti-inflammatory potential might be related, at least in part, to its chemopreventive activity.

Chlorfenapyr is a new formulated insecticide targeted against insecticide resistant species. Its application in targeting harmful aquatic insects may potentially contaminate aquatic environment. This study is to evaluate its genotoxic effects on non-targeted aquatic biota. The study assessed the genotoxic potentials of chlorfenapyr in African catfish (Clarias gariepinus) using the micronucleus (MN) test. Juvenile stage of C. gariepinus were exposed to different concentrations; 5.00 – 15.00 mgL-1 of chlorfenapyr for 96 hours, peripheral blood was collected through the caudal vein and examined for micronucleus induction in the erythrocytes. The tested concentrations of chlorfenapyr did not elicit significant [F (5, 18) = 0.167, p 0.971] increase in MN formation and other nuclear abnormalities in the peripheral erythrocytes of C. gariepinus. The outcome of this study gives credence to the view that chlorfenapyr is not clastogenic and or aneugenic to non-targeted aquatic vertebrate with reference to fish (C. gariepinus).

Omeprazole (OME), a most frequently used proton pump inhibitor in gastric acidosis, is evident to show many adverse effects, including genetic instability. This study evaluated toxicogenic effects of OME in Mus musculus. For this study, 40 male Swiss mice were divided into 8 groups (n = 5) and treated with OME at doses of 10, 20, and 40 mg/kg and/or treated with the antioxidants retinol palmitate (100 IU/kg) and ascorbic acid (2.0 μM/kg). Cyclophosphamide 50 mg/kg, (cytotoxic agent) and the vehicle were served as positive and negative control group, respectively. After 14 days of treatment, the stomach cells along with the bone marrow and peripheral blood lymphocytes were collected and submitted to the comet assay (alkaline version) and micronucleus test. Additionally, hematological and biochemical parameters of the animals were also determined inspect of vehicle group. The results suggest that OME at all doses induced genotoxicity and mutagenicity in the treated cells. However, in association with the antioxidants, these effects were modulated and/or inhibited along with a DNA repair capacity. Taken together, antioxidants (such as retinol palmitate and ascorbic acid) may be one of the best options to counteract OME-induced cytogenetic instability.

Heavy metals cadmium has been used as a yellow pigment due to its bright and lasting color. Considering the toxicity of cadmium, yellow iron oxide has been suggested as a substitute due to its cost-effectiveness. However, cellular and molecular safety information of yellow iron oxide is not fully understood. Metal-mediated cellular stress indicated by metallothionein 1 expression were measured by western blotting and qRT-PCR in cadmium- or iron oxide-treated HepG2 cells. Genotoxicity were detected using comet assay and micronuclei assay in HepG2 cells and rat liver tissue. Observed toxicological effects were quantified and scored on a scale bar for integrated analysis. Yellow iron oxide showed significantly low metallothionein 1 expression and genotoxicity in all results. This result indicates high potential of iron oxide as an alternative to cadmium. We demonstrated the comparative toxicity of the cadmium and yellow iron oxide in terms of stress-responsive biomarker expression and genotoxicity in HepG2 cells and rat liver tissue. Our study with the integrated strategy suggests usefulness of the yellow iron oxide as a substitute material in cadmium-containing products and reports useful tool to comprehensively assess the toxicity of suspected toxicants or newly developed materials.

Dioscorea Rhizome is commonly used in traditional herbal medicines for the treatment of diabetes, hyperthyroidism, liver damage, neuropathy, and asthma. Here, we investigated the genotoxicity potential of D. Rhizome water extract (DRWE) using three standard battery systems in accordance with the test guidelines of the Organisation for Economic Cooperation and Development and Ministry of Food and Drug Safety as well as the principles of Good Laboratory Practice. A bacterial reverse mutation test (Ames test) was performed using the direct plate incorporation method in the presence or absence of a metabolic activation system (S9 mixture). The tester strains used included four histidine auxotrophic strains of Salmonella typhimurium, TA100, TA1535, TA98, and TA1537, along with a tryptophan auxotrophic strain of Escherichia coli, WP2 uvrA. An in vitro chromosome aberration test was performed using CHL/IU cells originally derived from the lung of a female Chinese hamster in the presence or absence of the S9 mixture. An in vivo mouse bone marrow micronucleus test was performed using male ICR mice. The micronucleus was confirmed after observation of the micro-nucleated polychromatic. The Ames test showed that DRWE did not induce gene mutations at any dose level in any of the tested strains. Additionally, DRWE did not result in any chromosomal aberrations specified in the in vitro chromosomal aberration and in vivo micronucleus tests. These results showed that DRWE exhibited neither mutagenic nor clastogenic potential in either the in vitro or in vivo test systems.

OBJECTIVE The aim: of this work was to experimentally study the modifying role of toxic substances (phenol) in the manifestation of genotoxic and immunological changes in the body when exposed to a carcinogen (benzo[a]pyrene). PATIENTS AND METHODS Materials and methods: Investigations were carried out in the chronic experiment on white random-bred male mice. Genotoxic (micronucleus test), immunologic and pathomorphological methods were used. RESULTS Results: As a result of the experiment on white outbred mice during the isolated peroral administration of benzo[a]pyrene (a single dose of 0.1 mg) and in combination with phenol (single doses of 0.1 mg; 0.002 mg) a carcinogenic effect (forestomach papillomas) has been established as well as general patterns of the manifestation of genotoxic and immunological changes regarding carcinogenesis and their dependence on the dose and duration of the administration of the substances in the early stages of the experiment. The established patterns involved parallelism of development and unidirectionality of the genotoxic effect (increasing of micronucleus incidence) and suppression of the T-cell immunity by the end of the month as well as reliable negative correlation between them. CONCLUSION Conclusions: It has been established that phenol has a modifying effect on carcinogenesis, which was shown as an increase in the micronuclei frequency, intensification of immunosuppression in the early stages and an increase in the multiplicity factor of the development of forestomach tumors.

Introduction: Oral cancer is one of the ten most common causes of mortality in developing countries like India. A micronucleus (MN) is a small extra nucleus separated from the main one, generated during cellular division by late chromosomes or by chromosome fragments. Micronucleus is a potential biomarker for malignancy. Aim and Objectives: The study attempts to analyze micronuclei in buccal smear from patients with tobacco and related habits; and to determine its reliability as a biomarker for carcinogenesis. Study Design: A total of 400 consisting of normal subjects, patients with potentially malignant lesions and patients with malignant lesions were included in the study. Oral exfoliated cells were collected by scrapings of buccal mucosa of both control and study groups with a tooth brush. The scrapings collected from right and left buccal mucosa of each subject were studied under two separate slides. A total of 500 cells were examined from each slide. All the micronucleus cells located on each slide were examined again under the 100X magnification. Results: The P value for intergroup difference in average number of micronuclei in cells of buccal mucosa among all groups was