Genotoxic Damage Research Articles

Influences of l-ascorbic acid on cytotoxic, biochemical, and genotoxic damages caused by copper II oxide nanoparticles in the rainbow trout gonad cells-2

In parallel with the raising use of copper oxide nanoparticles (CuO NPs) in various industrial and commercial practices, scientific reports on their release to the environment and toxicity are increasing. The toxicity of CuO NPs is mostly based on their oxidative stress. Therefore, it is necessary to investigate the efficacy of well-known therapeutic agents as antioxidants against CuO NPs damage. This study aimed to investigate the mechanism of this damage and to display whether l-ascorbic acid could preserve against the cell toxicities induced by CuO NPs in the rainbow trout gonad cells-2 (RTG-2). While CuO NPs treatment significantly diminished cell viability, the l-ascorbic acid supplement reversed this. l-ascorbic acid treatment reversed the changes in expressions of sod1, sod2, gpx1a, and gpx4b genes while playing a supportive role in the changes in the expression of the cat gene induced by CuO NPs treatment. Moreover, CuO NPs treatment caused an upregulation in the expressions of growth-related genes (gh1, igf1, and igf2) and l-ascorbic acid treatment further increased these effects. CuO NPs treatment significantly up-regulated the expression of the gapdh gene (glycolytic enzyme gene) compared to the control group, and l-ascorbic acid treatment significantly down-regulated the expression of the gapdh gene compared to CuO NPs treatment. The genotoxicity test demonstrated that l-ascorbic acid treatment increased the genotoxic effect caused by CuO NPs by acting as a co-mutagen. Based on the findings, l-ascorbic acid has the potential to be sometimes inhibitory and sometimes supportive of cellular mechanisms caused by CuO NPs.

Characterization of the external exposome and its contribution to the clinical respiratory and early biological effects in children: The PROMESA cohort study protocol.

Air pollution contains a mixture of different pollutants from multiple sources. However, the interaction of these pollutants with other environmental exposures, as well as their harmful effects on children under five in tropical countries, is not well known. This study aims to characterize the external exposome (ambient and indoor exposures) and its contribution to clinical respiratory and early biological effects in children. A cohort study will be conducted on children under five (n = 500) with a one-year follow-up. Enrolled children will be followed monthly (phone call) and at months 6 and 12 (in person) post-enrolment with upper and lower Acute Respiratory Infections (ARI) examinations, asthma development, asthma control, and genotoxic damage. The asthma diagnosis will be pediatric pulmonologist-based and a standardized protocol will be used. Exposure, effect, and susceptibility biomarkers will be measured on buccal cells samples. For environmental exposures PM2.5 will be sampled, and questionnaires, geographic information, dispersion models and Land Use Regression models for PM2.5 and NO2 will be used. Different statistical methods that include Bayesian and machine learning techniques will be used for the ambient and indoor exposures-and outcomes. This study was approved by the ethics committee at Universidad Pontificia Bolivariana. To estimate i) The toxic effect of particulate matter transcending the approach based on pollutant concentration levels; ii) The risk of developing an upper and lower ARI, based on different exposure windows; iii) A baseline of early biological damage in children under five, and describe its progression after a one-year follow-up; and iv) How physical and chemical PM2.5 characteristics influence toxicity and children's health.

The Road to Malignant Cell Transformation after Particulate Matter Exposure: From Oxidative Stress to Genotoxicity.

In cells, oxidative stress is an imbalance between the production/accumulation of oxidants and the ability of the antioxidant system to detoxify these reactive products. Reactive oxygen species (ROS), cause multiple cellular damages through their interaction with biomolecules such as lipids, proteins, and DNA. Genotoxic damage caused by oxidative stress has become relevant since it can lead to mutation and play a central role in malignant transformation. The evidence describes chronic oxidative stress as an important factor implicated in all stages of the multistep carcinogenic process: initiation, promotion, and progression. In recent years, ambient air pollution by particulate matter (PM) has been cataloged as a cancer risk factor, increasing the incidence of different types of tumors. Epidemiological and toxicological evidence shows how PM-induced oxidative stress could mediate multiple events oriented to carcinogenesis, such as proliferative signaling, evasion of growth suppressors, resistance to cell death, induction of angiogenesis, and activation of invasion/metastasis pathways. In this review, we summarize the findings regarding the involvement of oxidative and genotoxic mechanisms generated by PM in malignant cell transformation. We also discuss the importance of new approaches oriented to studying the development of tumors associated with PM with more accuracy, pursuing the goal of weighing the impact of oxidative stress and genotoxicity as one of the main mechanisms associated with its carcinogenic potential.

Cytogenetic effects of [formula omitted]-particles in Allium cepa cells used as a biological indicator for radiation damages

Analysis of cytogenetics effects of ionizing radiation for flora and fauna is essential to determine the impact on these communities and may produce an efficient warning system to avoid harm to human health. Onion (Allium cepa) is a well-established in vivo standard model, and it is widely used in cytogenetics studies for different environmental pollutants. In this work, onion roots were exposed to 0.04–1.44 Gy of β-particles from a 90Sr/90Y source. We investigated the capacity of brief external exposures to β-particles on inducing cytogenetic damages in root meristematic cells of onion aiming to verify if onion can be used as a radiation-sensitive cytogenetic bioindicator. A nonlinear increase in the frequencies of chromosomal aberrations and cells with micronuclei was observed. Onion roots exposed to doses 0.13 Gy or higher of β-particles showed a significant difference (p<0.05) in these frequencies when compared to the unirradiated group. The frequencies of these endpoints showed to be suitable to assess the difference in the dose of beta radiation received from 0.36 Gy. Our research shows the potential of using cytogenetic effects in Allium cepa cells as a biological indicator for a first screening of genotoxic damages induced by brief external exposures to β-particles.

Assessment of genotoxicity induced by subchronic exposure to graphene in HaCaT human skin cell line

The applications of graphene-based materials (GBMs) and their processing involve prolonged contact with cellular barriers such as human skin. Even though the potential cytotoxicity of graphene has been studied in recent years, the impact of long-term graphene exposure has rarely been explored. We tested in the HaCaT epithelial cells, in vitro, the effect of subchronic treatments with sublethal doses of four different, well-characterized GBMs, two commercial graphene oxides (GO) and two few-layer graphenes (FLG). Cells were exposed weekly to low doses of the GBMs for 14 days, 30 days, 3 months, and 6 months. GBMs-cells uptake was assessed by confocal microscopy. Cell death and cell cycle were determined by fluorescence microscopy and cytometry. DNA damage was measured by comet assay and γ-H2AX staining, followed by the determination of p-p53 and p-ATR by immunolabeling. Subchronic exposure to different GBMs at noncytotoxic doses has potential genotoxic effects on HaCaT epithelial cells that can be recovered depending on the GBM and exposure time. Specifically, GO-induced genotoxicity can be detected after 14 and 30 days from treatment. At this time, FLG appears less genotoxic than GO, and cells can recover more quickly when genotoxic pressure disappears after some days of removal of the GBM. Long-term exposure, 3 and 6 months, to different GBMs induces permanent, nonreversible, genotoxic damage comparable to the exerted by arsenite. This should be considered for the production and future applications of GBMs in scenarios where low concentrations of the material interact chronically with epithelial barriers.

Genotoxic effects of oxyclozanide on hemocytes of Galleria mellonella (Lepidoptera: Pyralidae) larvae

Oxyclozanide is a salicylanilide derivative anthelmintic drug with a well-known effect on parasites that cause infections in humans and animals. In this study, the effect of oxyclozanide on DNA damage in hemocytes of Galleria mellonella (L.) (Lepidoptera: Pyralidae) larvae, which has been used as a model organism in many fields, was investigated. Hemolymph was collected from the last instar larvae (7th instar) reared on artificial diets containing oxyclozanide at different concentrations (0.003%, 0.03%, 0.3%, and 1.5%) under laboratory conditions and then hemocytes suspension was prepared. Genotoxic damage in hemocytes was determined by the comet assay which enables microscopically detecting DNA damage and is a very sensitive assay in chemical genotoxicity. When compared to the control group, tail length, tail DNA percent, and tail moment values were significantly increased parallel with increasing oxyclozanide concentrations. While the tail length was determined as 5.11 ± 0.46 μm in the control group, it was significantly increased in all tested groups to 13.17 ± 0.53, 27.98 ± 1.08, 98.44 ± 0.77, and 137.67 ± 0.74 μm, respectively. Similarly to tail length, tail DNA percentage and tail moment levels were also significantly increased from 12.86 ± 0.74 to 91.96 ± 0.31 at the highest concentration of oxyclozanide. These results showed that oxyclozanide caused DNA damage in the hemocytes of G. mellonella. It is also known that hemocytes are an important bioindicator in determining the genotoxicity of anthelmintics to be used as insecticides within environmentally friendly limits. It is thought that our results will contribute to the studies in this field.

Toxicological effects of cigarette butts for marine organisms

Cigarette butts (CBs), one of the most common litter items found on beaches, represent a still unexplored environmental hazard. This study aimed at a multidisciplinary characterization of their toxicological risks on marine organisms integrating chemical analyses of released compounds with a wide panel of biological responses, such as ecotoxicological bioassays on species of different trophic positions, molecular responses in an ex vivo model (Precision-Cut Tissue Slices, PCTS of mussels digestive glands), bioavailability and cellular biomarkers in mussels exposed to CBs in laboratory experiments. Trace metals, aliphatic and polycyclic aromatic hydrocarbons, nicotine and cotinine were released in artificial seawater after 24 h which determined a significant inhibition of bacterial bioluminescence, oyster embryo development and growth in different algal species. Modulation of peroxisomal proliferation and antioxidant gene expression was observed in mussels PCTS, while the in vivo exposure determined accumulation of chemicals and significant alterations of immune system, antioxidant and neurotoxic responses, peroxisomal proliferation and genotoxic damage. Using a quantitative Weight of Evidence model, the risks of CBs to the marine environment were summarized, highlighting the importance of integrating chemical analyses, batteries of ecotoxicological bioassays, molecular and cellular biomarkers to assess the impact of these hazardous materials on marine environment.

Systematization of research on the incidence of pesticides in people, use of biomarkers

Currently the use of pesticides in agriculture has expanded in the search for greater productivity. These products can harm people's health in various ways. These effects can be captured through the use of genotoxicity biomarkers. The objective of this research is to systematize studies on biomarkers of genotoxicity of people exposed to pesticides in South America. The PRISMA method was applied to determine the studies to be analyzed. 15 documents met the inclusion criteria. Among the adverse health effects perceived in studies are neurological, respiratory, dermatological and endocrine disorders, as well as an increased risk of cancer. The main biomarkers identified are the comet assay, the cytokinesis blockade micronucleus assay, and the buccal cytoma micronucleus assay. Polymerase chain reaction, chromosomal aberrations, flow cytometry, and fluorescence in situ hybridization were also taken into account. Limitations were determined by biomarker. The usefulness of using multiple biomarkers is highlighted for a more complete and precise evaluation of pesticide exposure and genotoxic damage in agricultural workers in South America. The establishment of protective measures for workers against the use of pesticides and opting for the use of pesticides of biological origin will contribute to the preservation of people's health

Chemical mechanisms of DNA damage by carcinogenic chromium(VI).

Hexavalent chromium is a firmly established human carcinogen with documented exposures in many professional groups. Environmental exposure to Cr(VI) is also a significant public health concern. Cr(VI) exists in aqueous solutions as chromate anion that is unreactive with DNA and requires reductive activation inside the cells to produce genotoxic and mutagenic effects. Reduction of Cr(VI) in cells is nonenzymatic and in vivo principally driven by ascorbate with a secondary contribution from nonprotein thiols glutathione and cysteine. In addition to its much faster rate of reduction, ascorbate-driven metabolism avoids the formation of Cr(V) which is the first intermediate in Cr(VI) reduction by thiols. The end-product of Cr(VI) reduction is Cr(III) which forms several types of Cr-DNA adducts that are collectively responsible for all mutagenic and genotoxic effects in Cr(VI) reactions with ascorbate and thiols. Some Cr(V) forms can react with H2O2 to produce DNA-oxidizing peroxo species although this genotoxic pathway is suppressed in cells with physiological levels of ascorbate. Chemical reactions of Cr(VI) with ascorbate or thiols lack directly DNA-oxidizing metabolites. The formation of oxidative DNA breaks in early studies of these reactions was caused by iron contamination. Production of Cr(III)-DNA adducts in cells showed linear dose-dependence irrespective of the predominant reduction pathway and their processing by mismatch repair generated more toxic secondary genetic lesions in euchromatin. Overall, Cr(III)-DNA adduction is the dominant pathway for the formation of genotoxic and mutagenic DNA damage by carcinogenic Cr(VI).

Fluoxetine induces oxidative stress-dependent DNA damage in human hepatoma cells

&lt;abstract&gt; &lt;p&gt;Fluoxetine is a selective serotonin reuptake inhibitor that is a commonly used drug for the treatment of depression and obsessive-compulsive disorders. Despite the positive effects of this drug, it seems to be associated with various side effects. Genotoxicity or DNA damage is an important side effect of some kinds of drugs. To date, the genotoxicity and cytotoxicity of fluoxetine are partially unknown. In the present study, some oxidative stress methods were used, such as ROS, MDA and GSH evaluation methods in HepG2 cells treated with fluoxetine (1–10 µM). A comet assay was used to evaluate the genotoxic effects of fluoxetine, and flow cytometry was used for apoptosis detection in these hepatic cells. Our data have shown that fluoxetine increased MDA and intracellular concentration of ROS significantly (P &amp;lt; 0.001), while the amount of GSH was reduced significantly (P &amp;lt; 0.001). Our results also indicated that fluoxetine increased the DNA damage of HepG2 cells. The tail percentage of DNA for control cells was 4%, but this percentage was 19%, 28% and 32% for 1, 5 and 10 µM of fluoxetine concentration, respectively (P &amp;lt; 0.01 and P &amp;lt; 0.001). The flow cytometry results have also shown increases in early and late apoptosis for fluoxetine (13.31% and 9.54%, respectively). In conclusion, the present study has shown that fluoxetine is able to induce oxidative stress-dependent DNA damage. Anyway, more studies are needed to accurately explore the molecular and cellular aspects of fluoxetine.&lt;/p&gt; &lt;/abstract&gt;

Assessment of Cytogenetic Damage in Flexographic Workers: Micronucleus Assay in Exfoliated Buccal Epithelial Cells.

Literature review revealed that chemicals used in the printing industry show an association between genotoxicity and occupational exposure. Flexography is one type of printing technique recently becoming popular because of its fast, cost-efficient, and high-quality label printing. The micronucleus (MN) is considered to be a reliable marker for genotoxic damage, and it has a close association with cancer incidences by determining the presence and the extent of the chromosomal damage. Because there are no studies on flexographic workers (FWs), this study was intended to analyze and evaluate the effect of occupational exposure on the MN frequency of buccal epithelial cells. The study comprised 100 FWs and 100 age-matched healthy controls with and without smoking habits. Buccal epithelial cells were collected from all subjects by using a cytobrush, followed by staining with Feulgen fast green. The MN frequency was recorded for each individual using the Tolbert et al. criteria. Data was statistically analyzed by using one-way analysis of variance and the posthoc test. FWs with smoking habits showed a significant increase in MN frequency (1.86 ± 1.77) than workers without the habit (1.02 ± 1.08) and controls (with the habit 1.26 ± 1.33 and without the habit 0.62 ± 0.92). However, there was no significant increase of MN in FWs without the habit when compared with controls. This study observed the cytogenetic damage in FWs and concludes that these workers are at greater risk for genotoxicity, and the MN assay can serve as a useful biomarker.

Evaluation of Clastogenic/Aneugenic Damage Using the FISH Micronucleus Assay in Mice Exposed to Chromium (VI).

Exposure to chromium (VI) [Cr(VI)] has been postulated to be associated with the induction of cancer. In vivo studies utilizing biomarkers of genotoxic damage could aid in elucidating the mechanisms underlying the genotoxic effects of Cr(VI) and their relationship with carcinogenesis. In this study, the origin (clastogenic and/or aneugenic damage) and kinetics of micronuclei (MN) induced by Cr(VI) were investigated. Hsd:ICR female mice were divided into groups of five individuals each. MN kinetics were measured in groups treated with 20 or 25 mg/kg CrO3 intraperitoneally using acridine orange-coated slides in peripheral blood obtained from the caudal vein 0, 12, 24, 36, 48, 60, and 72 h after treatment. Whereas identification of MN with centromeric DNA (MNK+) was measured at the dose of 20 mg/kg of CrO3, using fluorescence in situ hybridization (FISH) with a centromere-specific probe in peripheral blood obtained at 0, 12, and 48 h after treatment. Control groups were administered vehicle only. Total MN were quantified and the clastogenic/aneugenic effects of Cr(VI) were evaluated based on the proportion of MNK+ versus micronuclei without centromeric DNA (MNK-). There was a significant increase in MN frequencies beginning at 12 h in the Cr(VI)-treated groups demonstrating its genotoxicity. When calculating the MNK+ as a percentage of the total MN, the increase was significant beginning 12 h after treatment. The fact that the MNK+ and MNK- were observed at both evaluation times corroborates Cr(VI) as a genotoxic agent and demonstrates that both clastogenic and aneugenic damages are involved in the formation of MN.

Evaluation of Genotoxicity induced by Cobalt to Freshwater Fish, Cirrhina mrigala using Micronuclei Assay

Due to industrial advancement, a variety of toxic chemicals including metals are released into the aquatic environment which not only disturbs the physico-chemical properties of the water bodies but also influences the aquatic food chain to cause physiological and cytogenetic alternations in the aquatic animals. Metals have the ability to produce reactive oxygen species (ROS) that would cause the oxidative of nucleic acid. Micronucleus test has been commonly used for the estimation of biological impacts of water pollutants on genotoxic damage in fish. Therefore, the present research work was designed to check the genotoxic potential of cobalt for fish Cirrhinus mrigala by using a micronuclei assay. Fish were exposed to the various sub-lethal concentrations of cobalt metal such as 2/3rd, 1/3rd, 1/4th, and 1/5th of LC50 concentration for one month and sampling was done after 10 days intervals. Blood sample from the caudal vein of fish was collected to see the micronuclei and binucleated nuclei. Results showed that all test concentrations induced micronuclei and binucleated nuclei in peripheral erythrocytes of C. mrigala. Maximum nuclear abnormalities in peripheral erythrocytes of C. mrigala were observed in 2/3rd concentration followed by the orders: 1/3rd 1/4th 1/5th.Due to industrial advancement, a variety of toxic chemicals including metals are released into the aquatic environment which not only disturbs the physico-chemical properties of the water bodies but also influences the aquatic food chain to cause physiological and cytogenetic alternations in the aquatic animals. Metals have the ability to produce reactive oxygen species (ROS) that would cause the oxidative of nucleic acid. Micronucleus test has been commonly used for the estimation of biological impacts of water pollutants on genotoxic damage in fish. Therefore, the present research work was designed to check the genotoxic potential of cobalt for fish Cirrhinus mrigala by using a micronuclei assay. Fish were exposed to the various sub-lethal concentrations of cobalt metal such as 2/3rd, 1/3rd, 1/4th, and 1/5th of LC50 concentration for one month and sampling was done after 10 days intervals. Blood sample from the caudal vein of fish was collected to see the micronuclei and binucleated nuclei. Results showed that all test concentrations induced micronuclei and binucleated nuclei in peripheral erythrocytes of C. mrigala. Maximum nuclear abnormalities in peripheral erythrocytes of C. mrigala were observed in 2/3rd concentration followed by the orders: 1/3rd 1/4th 1/5th.

Fate of micronuclei and micronucleated cells after treatment of HeLa cells with different genotoxic agents

Although micronuclei are well-known biomarkers of genotoxic damage, the biological consequences of micronucleus induction are only poorly understood. To further elucidate these consequences, HeLa cells stably expressing histone 2B coupled with green fluorescent protein were used for long-term live cell imaging to investigate the fate of micronuclei and micronucleated cells after treatment of cells with various genotoxic agents (doxorubicin (20, 30 and nM), tert-butyl hydroperoxide (tBHP, 50, 100 and 150 µM), radiation (0.5, 1 and 2 Gy), methyl methanesulfonate (MMS, 20, 25 and 30 µg/ml) and vinblastine (1, 2 and 3 nM)). Most micronuclei persist for multiple cell cycles or reincorporate while micronucleated cells were more prone to cell death, senescence and fatal mitotic errors compared to non-micronucleated cells, which is consistent with previous studies using etoposide. No clear substance-related effects on the fate of micronuclei and micronucleated cells were observed. To further investigate the fate of micronuclei, extrusion of micronuclei was studied with treatments reported as inducing the extrusion of micronuclei. Since extrusion was not observed in HeLa cells, the relevance of extrusion of micronuclei remains unclear. In addition, degradation of micronuclei was analysed via immunostaining of γH2AX, which demonstrated a high level of DNA damage in micronuclei compared to the main nuclei. Furthermore, transduction with two reporter genes (LC3B-dsRed and LaminB1-dsRed) was conducted followed by long-term live cell imaging. While autophagy marker LC3B was not associated with micronuclei, Lamin B1 was found in approximately 50% of all micronuclei. While degradation of micronuclei was not observed to be a frequent fate of micronuclei, the results show impaired stability of DNA and micronuclear envelope indicating rupture of micronuclei as a pre-step to chromothripsis.

Genotoxicity and Reproductive Risk in Workers Exposed to Pesticides in Rural Areas of Curicó, Chile: A Pilot Study

Significant risks to human health have been associated with chronic exposure to low doses of pesticides, a situation which may be frequent among agricultural workers. In this context, and regarding the agricultural-based economy of central Chile, we aimed to explore the genotoxic damage in agricultural workers and reproductive risk among women in rural and urban areas of Curicó, a traditional agricultural district in Chile. Hence, we sampled a group of rural agricultural workers associated with pesticide management (n = 30) and an urban unexposed group (n = 30). Our results showed that the agricultural workers had higher micronuclei frequencies (MN: β = 13.27; 95% CI low = 11.08, CI high = 15.47) and women had a 40-fold higher risk of reproductive problems (OR = 40.32; 95% CI low = 2.60, CI high = 624.31) than the unexposed group. The factor analysis of mixed data (FAMD) showed that neither the sex nor smoking habits appear to define the ordination of the data. Nevertheless, the exposure level did segregate them in the multidimensional space (explained variance: 35.38% dim-1; 18.63% dim-2). This pilot study highlights the higher risks of biological conditions negatively associated with the health of agricultural workers.

Cisplatin-induced cell death increases the degradation of the MRE11-RAD50-NBS1 complex through the autophagy/lysosomal pathway

Cisplatin and other platinum-based anticancer agents are among the most widely used chemotherapy drugs in the treatment of different types of cancer. However, it is common to find patients who respond well to treatment at first but later relapse due to the appearance of resistance to cisplatin. Among the mechanisms responsible for this phenomenon is the increase in DNA damage repair. Here, we elucidate the effect of cisplatin on the MRN (MRE11-RAD50-NBS1) DNA damage sensor complex. We found that the tumor suppressor FBXW7 is a key factor in controlling the turnover of the MRN complex by inducing its degradation through lysosomes. Inhibition of lysosomal enzymes allowed the detection of the association of FBXW7-dependent ubiquitylated MRN with LC3 and the autophagy adaptor p62/SQSTM1 and the localization of MRN in lysosomes. Furthermore, cisplatin-induced cell death increased MRN degradation, suggesting that this complex is one of the targets that favor cell death. These findings open the possibility of using the induction of the degradation of the MRN complex after genotoxic damage as a potential therapeutic strategy to eliminate tumor cells.

An endophytic Schizophyllum commune possessing antioxidant activity exhibits genoprotective and organprotective effects in fresh water fish Channa punctatus exposed to bisphenol A

BackgroundOxidative stress is responsible for the onset of several chronic and degenerative diseases. Exogenous supply of antioxidants is reported to neutralize the effects of oxidative stress. Several synthetic antioxidants suffer from various side effects which necessitates the exploration of antioxidant compounds from natural sources. Endophytic fungi residing in the plants are gaining the attention of researchers as a source of novel antioxidants. Majority of the research conducted so far on endophytic fungi has been restricted to the members of phylum ascomycota. Basidiomycota, inspite of their immense bioactive potential remain relatively unexploited. This study aimed to assess the ameliorative effects of an endophytic Schizophyllum commune (basidiomycetous fungus) against oxidative stress associated altered antioxidant levels, genotoxicity and cellular damage to different organs in bisphenol A exposed fresh water fish Channa punctatus.ResultsGood antioxidant and genoprotective potential was exhibited by S. commune extract in in vitro studies conducted using different antioxidant, DNA damage protection, and cytokinesis blocked micronuclei assays. In vivo studies were performed in fresh water fish Channa punctatus exposed to bisphenol A. A significant decrease in the considered parameters for DNA damage (% micronuclei and comet assay) were recorded in fish treated with S. commune extract on comparison with untreated bisphenol A exposed group. The S. commune extract treated fish also exhibited an increase in the level of antioxidant enzymes viz. catalase, superoxide dismutase and glutathione reductase as well as histoprotective effect on various organs. GC-MS analysis revealed the presence of 3-n-propyl-2,4-pentanedione, n-heptadecanol-1, trans-geranylgeraniol, 3-ethyl-2-pentadecanone, 1-heneicosanol and squalene as some of the compounds in S. commune extract.ConclusionThe study highlights the significance of an endophytic basidiomycetous fungus S. commune as a source of antioxidant compounds with possible therapeutic potential.

Toxicity of Glycyl-l-Prolyl-l-Glutamate Pseudotripeptides: Cytotoxic, Oxidative, Genotoxic, and Embryotoxic Perspectives.

The tripeptide H-Gly-Pro-Glu-OH (GPE) and its analogs began to take much interest from scientists for developing effective novel molecules in the treatment of several disorders including Alzheimer's disease, Parkinson's disease, and stroke. The peptidomimetics of GPEs exerted significant biological properties involving anti-inflammatory, antiapoptotic, and anticancer properties. The assessments of their hematological toxicity potentials are critically required for their possible usage in further preclinical and clinical trials against a wide range of pathological conditions. However, there is so limited information on the safety profiling of GPE and its analogs on human blood tissue from cytotoxic, oxidative, and genotoxic perspectives. And, their embryotoxicity potentials were not investigated yet. Therefore, in this study, measurements of mitochondrial viability (using MTT assay) and lactate dehydrogenase (LDH) release as well as total antioxidant capacity (TAC) assays were performed on cultured human whole blood cells after treatment with GPE and its three novel peptidomimetics for 72 h. Sister chromatid exchange (SCE), micronucleus (MN), and 8-oxo-2-deoxyguanosine (8-OH-dG) assays were performed for determining the genotoxic damage potentials. In addition, the nuclear division index (NDI) was figured out for revealing their cytostatic potentials. Embryotoxicity assessments were performed on cultured human pluripotent NT2 embryonal carcinoma cells by MTT and LDH assays. The present results from cytotoxicity, oxidative, genotoxicity, and embryotoxicity testing clearly propounded that GPEs had good biosafety profiles and were trouble-free from the toxicological point of view. Noncytotoxic, antioxidative, nongenotoxic, noncytostatic, and nonembryotoxic features of GPE analogs are worthwhile exploring further and may exert high potentials for improving the development of novel disease-modifying agents.

Study of micronuclei as a potent biomarker in breast cytology aspirates

: Micronuclei scoring can be used as a bio-marker of genotoxic and chromosomal damage. Fine needle aspiration cytology (FNAC) is applied as the primary tool for diagnosis in breast masses because of its ease and rapidity. Micronucleus (MN) scoring is carried out in benign (fibroadenoma) and malignant (infiltrating ductal carcinoma) breast lesions to evaluate the role of Micronuclei as a biomarker in breast carcinomas.: To study Micronuclei (MN) scores as a biomarker on breast cytology aspirated smears. This was a prospective study done for duration of two years in the Department of Pathology, A.C.S Medical College and Hospital, Chennai. The features of micronuclei in 60 breast aspirate smears were studied and compared in benign conditions, proliferative and malignant conditions.The most common diagnosis was of fibroadenoma seen in 38 (63.3%) cases. Adenosis was seen in 10 (16.6%) cases. Usual ductal hyperplasia in 6.6% cases and Invasive ductal carcinomas in 6 (10%) cases. The Average Micronucleus score/1000 cells and the range of micronucleus score was higher in malignancy as compared to benign conditions. : Micronuclei can be used as a biomarker on fine needle aspiration cytology smears of breast lesions. An increase in micronuclei is usually seen in malignant conditions as compared to benign tumours. Attention to features of micronuclei can give a clue to the presence of malignancy.

Genotoxic damage and apoptosis in rat glioma (F98) cell line following exposure to bromuconazole

Bromuconazole, a fungicide from the triazole family, is widely used to protect the crop from various fungal contaminations to increase product quality and productivity. Although the massive use of bromuconazole poses a serious risk to human health, the exact mechanism of bromuconazole toxicity, especially on brain support cells, called glia cells, remains unclear so far. This study aimed to determine the mechanism of cytotoxicity and genotoxicity of bromuconazole via inspection of apoptotic death in rat glioma (F98) cells. We observed that bromuconazole treatment caused concentration-dependent cell death with an IC50 of 60 µM, and disruption of the cytoskeleton was observed via immunocytochemical analysis. Further, bromuconazole inhibits cell proliferation, it arrests the cell cycle in the G0/G1 phase and so inhibits DNA synthesis. Genotoxic analysis showed that bromuconazole exposition causes DNA fragmentation (comet assay) and nuclear condensation (DAPI staining). Apoptotic cell death was confirmed through: positive Annexin-V/FITC-PI dyes, p53 and Bax overexpression, Bcl2 repression, an increase in Bax/BCL-2 ratios of the mRNA, mitochondrial membrane depolarization, and an increase of caspase-3 activity. All these results demonstrate that bromuconazole exerts its cytotoxic and genotoxic effects through apoptotic cell death, which could implicate mitochondria.