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Purpose: Determination of the value of relative biological effectiveness (RBE) of heavy charged ions in vivo is an important task for their optimal use in particle radiotherapy. The aim of this study was to determine the RBE value of a beam of carbon ions with an energy of 450 MeV/nucleon in different regions of the Bragg curve in irradiation of mice at low, medium, and high doses in comparison with X-ray radiation. Materials and methods: SHK mice (n = 330) were irradiated in three regions of the Bragg curve in the dose range of 0–1.5 Gy for cytogenetic damage detection and at a dose of 6.5 Gy for determination of 30-day survival. For irradiation of mice in the Bragg peak, two widths of a spread-out Bragg peak (SOBP) were used: 10 mm (LET ∼100 keV/µm) and 30 mm (LET ∼39 keV/µm). Results: The RBE value was 0.8–0.9 before the Bragg peak (LET ∼15 keV/µm) and 0.8 after the peak (LET ∼5 keV/µm), and did not depend on the determination method, despite the differences in LET values. The RBE value determined by the micronucleus test was 1.1–1.7 for the 10-mm-wide SOBP and 1.0–1.3 for the 30-mm-wide SOBP, with the highest RBE value obtained in the low-dose region upon irradiation of mice in the 10-mm-wide Bragg peak. The RBE values in the high-dose region determined by the 30-day survival test lay in the range from 1.4 to 2.6 depending on the width of the Bragg peak and the chosen criterion for calculating the value. The RBE values in the 10-mm-wide Bragg peak (LET ∼100 keV/µm) were higher than those in the 30-mm-wide Bragg peak (LET ∼39 keV/µm) at all used criteria. Conclusions: The present findings suggest that there is the complex relationship between LET and organism response to accelerated charged particle radiation, and the contribution of specific factors and mechanisms must be further considered. [ABSTRACT FROM AUTHOR]

Although the last pandemic created an urgency for development of vaccines, there was a continuous and concerted effort to search for therapeutic medications among existing drugs with different indications. One of the medications of interest that underwent this change was infliximab (IFM). This drug is used as an anti-inflammatory, predominantly in patients with Crohn 's disease, colitis ulcerative, and rheumatoid arthritis. In addition to these patients, individuals infected with Coronavirus Disease (COVID-19) were administered this chimeric monoclonal antibody (IMF) to act as an immunomodulator for patients in the absence of comprehensive research. Consequently, the present study aimed to examine the genotoxic effects attributed to IFM treatment employing different assays in vivo using mouse Mus musculus. Therefore, IFM was found to induce genotoxic effects as evidenced by the comet assay but did not demonstrate genotoxic potential utilizing mouse bone marrow MN test. The results of evaluating the expression of the P53 and BCL-2 genes using RT-qPCR showed stimulation of expression of these genes at 24 hr followed by a decline at 48 hr. Although the comet assay provided positive results, it is noteworthy that based upon negative findings in the micronucleus test, the data did not demonstrate significant changes in the genetic material that might affect the therapeutic use of IFM. The stimulation of expression of P53 and BCL-2 genes at 24 hr followed by a decline at 48 hr suggest a transient, if any, effect on genetic material. However, there is still a need for more research to more comprehensively understand the genotoxic profile of this medication. [ABSTRACT FROM AUTHOR]

Vigabatrin (VGB) is a gammaaminobutyric acid-ergic (GABA-ergic) antiepileptic drug (AED) and is one of 2 approved drugs available to treat infantile spasms (IS). The aim of this study is to elucidate conflicting data on the toxic effects of VGB and to obtain detailed information about its possible cytogenotoxic effects in human lymphocytes. For this purpose, in vitro Chromosomal Aberration (CA), Sister Chromatid Exchange (SCE), Micronucleus (MN) tests, and Comet Assay were performed to determine possible genotoxic and cytotoxic effects of VGB. In addition, the binding energy level of VGB to DNA was determined in silico by molecular docking. The highest concentration (80 μg/ml) of VGB increased the SCE, CA, MN and micronucleated binuclear cell (BNMN) frequency significantly compared to the control after 24 and 48 hours of treatment. In the tail density and tail length parameters, the dose-dependent increase was found to be statistically significant compared to the control. At the 40 and 80 μg/ml concentrations of VGB for 48 hours caused a statistically significant increase in both CA/Cell and AC percentages, while MI and NDI decreased only significantly at the highest concentration (80 µg/ml) causing. In the Comet Assay head density, tail density and tail length parameters, the dose-dependent increase was found to be statistically significant compared to the control. Also, the in silico molecular docking analysis showed that VGB interacts with B-DNA close to the threshold binding energy. The lowest negative free binding energy (ΔG binding) was found as −5.13 kcal/mol. In conclusion, all results are evaluated together, it has been determined that VGB has cytogenotoxic effects in vitro and binds to DNA in silico with significant free binding energy. [ABSTRACT FROM AUTHOR]

Hydroxycoumarins are an important source of biologically active compounds. Previous studies have shown that the number and position of the hydroxyl substituents in the scaffold play an important role for the observed biological activity. In the present study, 3-(3-hydroxyphenyl)-7-hydroxycoumarin was synthesized, and potential cytogenotoxic effects determined in human HepG2/C3A cells displaying phase 1 and phase 2 enzymes (metabolizing cell ability) and compared to human peripheral blood mononuclear cells (PBMC) without xenobiotics metabolizing capacity. Cell viability was determined with concentrations between 0.01 and 10 µg/ml of 3-(3-hydroxyphenyl)-7-hydroxycoumarin using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) and trypan blue tests. Genotoxicity was determined utilizing the comet assay, and the clastogenic/aneugenic potential employing the micronucleus (MN) test. The results of the in vitro cytotoxicity assays showed a significant decrease in cell viability of PBMC following exposure to 10 µg/ml concentration of the studied compound after 48 and 72 hr. Comet assay observations noted significant DNA damage in PBMC after 4 hr treatment. No marked cytogenotoxic effects were found in HepG2/C3A cells. No chromosomal mutations were observed in both cell lines. It is important to note that 3-(3-hydroxyphenyl)-7-hydroxycoumarin may exert beneficial pharmacological actions at the low micromolar range and with half-life less than 24 hr. Therefore, the results obtained encourage the continuation of studies on this new molecule for medicinal purposes, but its potential toxicity at higher concentrations and longer exposure times needs to be investigated in further studies. [ABSTRACT FROM AUTHOR]

Oenothein B (OeB) is a dimeric ellagitannin with potent antioxidative, antitumor, immunomodulatory, and anti-inflammatory properties. Despite the promising activities of OeB, studies examining the genotoxic or protective effects of this ellagitannin on DNA are scarce. Therefore, to further comprehensively elucidate the chemopreventive profile of OeB, the aim of this study was to evaluate the mutagenic and antimutagenic actions of OeB using Salmonella typhimurium strains with the Ames test. The micronucleus (MN) test and comet assay were used to assess the anticytotoxic and antigenotoxic effects of OeB on mouse bone marrow cells following differing treatments (pre-, co-, and post-treatment) in response to cyclophosphamide (CPA)-induced DNA damage. In addition, histopathological analyses were performed to assess liver and kidney tissues of Swiss Webster treated mice. Our results did not detect mutagenic or antimutagenic activity attributed to OeB at any concentration in the Ames test. Regarding the MN test, data showed that this ellagitannin exerted antigenotoxic and anticytotoxic effects against CPA-induced DNA damage under all treatment conditions. However, no anticytotoxic action was observed in MN test after pre-treatment with the highest doses of OeB. In addition, OeB demonstrated antigenotoxic effects in the comet assay for all treatments. Histopathological analyses indicated that OeB attenuated the toxic effects of CPA in mouse liver and kidneys. These findings suggest that OeB exerted a chemoprotective effect following pre- and co-treatments and a DNA repair action in post-treatment experiments. Our findings indicate that OeB protects DNA against CPA-induced damaging agents and induces post-damage DNA repair. [ABSTRACT FROM AUTHOR]

Two different drug groups, typical (classic) and atypical (new), are used in the treatment of schizophrenia. Aripiprazole, an atypical antipsychotic chemical, is the active ingredient of the drug Abilify. This study was conducted to determine the possible genotoxic effect of aripiprazole. For this purpose, four different doses of aripiprazole (5; 10; 20, and 40 µg/mL) were examined with Chromosome Abnormality (CA), Sister Chromatid Exchange (SCE), Micronucleus (MN) tests. Based on these tests, Proliferation Index (PI), Percent Abnormal Cells (AC), Mitotic Index (MI), Micronuclear Binuclear Cell (MNBN), and Nuclear Division Index (NDI) levels were determined in human peripheral lymphocytes treated for 24 and 48 hours. Also, to determine possible binding sites of Aripiprazole on B-DNA molecular docking analysis was performed using AutoDock 4.0 (B-DNA dodecamer, PDB code: 1BNA). Aripiprazole binds to B-DNA with a very significant free binding energy (–11.88 Kcal/mol). According to our study, aripiprazole did not significantly change SCE, CA, AC percentage, MN frequencies when compared with control. According to these results, aripiprazole does not have a genotoxic effect. At the same time, no significant change was observed in the PI, MI, and NDI frequencies when compared with the control. In line with these results, it was observed that the use of aripiprazole in the treatment of schizophrenia did not pose any acute genotoxic and cytotoxic risk. [ABSTRACT FROM AUTHOR]

Sevelamer hydrochloride (SH) and calcium carbonate (CaCO3) are two agents included in the phosphate-binding group which are frequently prescribed in the treatment of patients with hyperphosphatemia. However, there are no satisfactory studies on the genotoxic effects of SH in vitro. This study was conducted to reveal the genotoxic and/or cytotoxic potential of these two drugs in cultured human peripheral lymphocytes. Human peripheral lymphocytes were treated with SH and CaCO3 at sublethal concentrations for 24 or 48 h for micronucleus assay and 1 h in the comet assay. CaCO3 and SH stimulated a slight increase in micronucleus formation however this increase was not significant compared to the control group. According to the findings of the comet test, only one concentration of the SH caused significant DNA damage (2 mg/ml, 48 h) whereas CaCO3 did not cause important DNA breakage. No significant oxidative damage or anti-radical effect caused by test substances was observed on the pure pBR322 plasmid DNA in a cell-free medium. Also, it was found that the drugs were devoid of mutagenic activity in the Ames test, but had a weak cytotoxic effect. Both test substances, particularly SH, significantly reduced the nuclear division index compared to the control group. In conclusion, the cytotoxic effect of SH was evident on the basis of in vitro tests and slightly higher than CaCO3. [ABSTRACT FROM AUTHOR]

The opioid agonist hydromorphone is indicated for the management of severe acute and chronic pain given that alternate treatments are insufficient. While the genotoxicity profile of hydromorphone is well investigated, little is known about the genotoxic potential of its impurities. In this study, 2,2-bishydromorphone was tested in silico and in vitro for both its mutagenic potential in an Ames test performed with Salmonella typhimurium and Escherichia coli tester strains up to a maximum concentration of 5 mg per plate in the absence and presence of metabolic activation. Furthermore, it was tested for its ability to induce micronuclei in TK6 cells in a micronucleus test up to a maximum concentration of 500 µg/mL with or without an exogenous metabolic activation system. 2,2-Bishydromorphone did not reveal any potential for inducing mutagenicity or clastogenicity under the conditions of the respective tests and is therefore considered non-mutagenic and non-clastogenic/aneugenic in vitro. These results are in line with negative in silico quantitative structure-activity relationship (QSAR) prediction for 2,2-bishydromorphone mutagenicity and clastogenicity and provide evidence of good correlation of in silico and in vitro data. Conclusively, these studies add important new clinically relevant information on the safety of hydromorphone as the impurity of 2,2-bishydromorphone is proven to be non-mutagenic and non-clastogenic. [ABSTRACT FROM AUTHOR]

Plants with medicinal potential may also produce adverse effects in humans. This seems to be the case for the species Rubus rosifolius, where preliminary studies demonstrated genotoxic effects attributed to extracts obtained from leaves and stems of this plant using on HepG2/C3A human hepatoma cells as a model. Considering the beneficial properties of this plant as an antidiarrheal, analgesic, antimicrobial, and antihypertensive and its effects in the treatment of gastrointestinal diseases, the present study was developed with the aim of determining the cytotoxic and genotoxic potential of extracts of leaves and stems of R. rosifolius in primary without metabolic competence in human peripheral blood mononuclear cells (PBMC). Cell viability analyses at concentrations of between 0.01 and 100 µg/ml of both extracts did not markedly affect cell viability. In contrast, assessment of the genotoxic potential using the comet assay demonstrated significant damage to DNA within PBMC from a concentration of 10 µg/ml in the stem extract, and a clastogenic/aneugenic response without cytokinesis-block proliferation index (CBPI) alterations at concentrations of 10, 20, or 100 µg/ml for both extracts. Under our experimental conditions, the data obtained demonstrated genotoxic and mutagenic effects attributed to extracts from leaves and stems of R. rosifolius in cells in the absence of hepatic metabolism. [ABSTRACT FROM AUTHOR]

Coumarins and chalcones are compounds widely found in plants or obtained by synthetic methods which possess several biological properties including antioxidant, anti-inflammatory, and antitumor effects. A series of coumarin-chalcone hybrids were synthesized to improve their biological actions and reduce potential adverse effects. Considering the applications of these molecules, a coumarin-chalcone hybrid [7-methoxy-3-(E)-3-(3,4,5-trimethoxyphenyl) acryloyl-2 H-chromen-2-one] (4-MET) was synthesized and the genotoxic, cytotoxic, and protective effects assessed against damage induced by different mutagens. First, in silico tools were used to predict biological activity of 4-MET which indicated a chemopreventive potential. Subsequently, the genotoxic/antigenotoxic activities of 4-MET were determined both in vitro (Ames test) and in vivo (micronucleus (MN) test and comet assay). In addition, molecular docking simulations were performed between 4-MET and glutathione reductase, an important cellular detoxifying enzyme. Our results indicated that 4-MET was not mutagenic in the Ames test; however, when co-treated with sodium azide or 4-nitroquinoline 1-oxide (4-NQO), 4-MET significantly reduced the harmful actions of these mutagens. Except for a cytotoxic effect after 120 hr treatment, 4-MET alone did not produce cytotoxicity or genotoxicity in the MN test and comet assay. Nonetheless, all treatments of 4-MET with cyclophosphamide (CPA) showed a chemoprotective effect against DNA damage induced by CPA. Further, molecular docking analysis indicated a strong interaction between 4-MET and the catalytic site of glutathione reductase. These effects may be related to (1) damage prevention, (2) interaction with detoxifying enzymes, and (3) DNA-repair induction. Therefore, data demonstrated that 4-MET presents a favorable profile to be used in chemopreventive therapies. [ABSTRACT FROM AUTHOR]

Carboplatin is amongst the most commonly used anticancer drugs for the management of several human malignancies. However, it has displayed genotoxic properties against normal cells. Evaluation of natural products for their protective effects against chemotherapeutic drug induced toxicity has been growing in recent years. A naturally occurring flavonoid, chrysin, has strong antioxidant abilities and protects against DNA impairment. This study used multiple assays to evaluate the levels of damage to DNA in normal cells and to examine any possible protective role of chrysin against such damage. Male BALB/c mice were administered chrysin orally in two doses of 20 and 40 mg/kg for 10 consecutive days and then a single injection of carboplatin [90 mg/kg body weight (b.w.)] was administered intraperitoneally to induce carboplatin toxicity. 24 h after the carboplatin injection, mice were sacrificed. DNA damage was evaluated using several genotoxicity tests (8-Hydroxydeoxy-guanosine marker, comet assay, micronucleus test, and chromosomal aberration assay) to identify diverse types of damage to the DNA. The results suggest that pretreatment with chrysin significantly decreased the level of DNA damage caused by carboplatin probably due to its potent antioxidant traits. Therefore, chrysin can be considered to be developed as a chemoprotective agent against chemotherapy associated side-effects. [ABSTRACT FROM AUTHOR]

Methanol extracts of A. absinthium, A. annua, A vulgaris, A. scoparia, and A. alba from Serbia at concentrations of 1.00; 2.00 and 4.00 μg/ml, and as pure compounds identified in examined extracts (ferulic acid, rutin, rosmarinic acid, and quercetin) were examined for their effects on micronucleus distribution in human lymphocytes in vitro. All extracts greatly reduced the number of micronuclei in the concentration of 2.00 μg/ml comparing to the control, whereby A. alba extract exhibited the most prominent effect on decreasing frequency of micronucleus (45.2%), followed by extracts of A. vulgaris, A. absinthium, A. scoparia and A. annua. The same declining trend was observed for the extracts at concentrations of 4.00 µg/ml, and 1.00 µg/ml, respectively. Among pure compounds (concentration 2.00 μg/ml), rutin showed the most pronounced effect on decreasing frequency of micronucleus (41.7%), higher than ferulic acid, quercetin, and rosmarinic acid comparing to the control. [ABSTRACT FROM AUTHOR]

Pistacia lentiscus L. is one of the most popular medicinal plants attributed to its beneficial properties on human health. However, few toxicogenetic studies have been carried out. Therefore, the aim of this study was to examine the potential genotoxic/antigenotoxic and mutagenic/antimutagenic properties of oil, ethyl acetate and ethanolic extracts of P. lentiscus L. fruits using in vitro the Ames and Umu assays, as well as in vivo micronucleus (MN) test. Extracts did not exert any significant mutagenic/genotoxic effects but provided protection against standard mutagenic and genotoxic agents including 2 nitrofluorene (2-NF) at 2.5 and 5 µg/ml; sodium azide at 5 and 10 µg/ml; 3-methylcholanthrene (3-MC) at 25 and 50 μg/ml; cyclophosphamide (CP) at 50 and 100 μg/ml; 4-nitroquinoline 1-oxide (4-NQO) at 0.05 µg/ml and 2-amino-anthracene (AA) at 0.2 µg/ml. Further, cytotoxicity and selectivity were examined on human hepatocarcinoma (HepG2), and MCF-7 breast cancer cell lines as well as a human normal-like fibroblast cell line (TelCOFS02MA) using MTT assay. Among all extracts, PF1 (ethanolic) showed the most significant selectivity index (SI) (HepG2:11.98; MCF7:4.83), which led to further investigations using an animal model. Oral administration of PF1 (125–1000 mg/kg b.w.) significantly decreased the number of micronucleated cells in CP -initiated (50 mg/kg b.w.) mice, while the number of micronucleated reticulocytes (MNRET), micronucleated polychromatic erythrocytes (MNPCE) or mitotic index (MI) were not markedly affected. Further, PF1 significantly enhanced catalase (CAT) and superoxide dismutase (SOD) activities in the livers and kidneys of these animals. The obtained results indicated the beneficial properties of P. lentiscus L. fruits for use in therapy against harmful effects of genotoxic and mutagenic agents. However, while promising it should be noted that the obtained results are preliminary and need to be confirmed prior to therapeutic use. [ABSTRACT FROM AUTHOR]

Medicinal plants have always been used for therapeutic purposes; however, some plants may contain toxic and mutagenic substances. The aim of this study was to assess the cytotoxic, genotoxic, mutagenic, antioxidant, antigenotoxic, and antimutagenic effects of the bark ethanolic extract of Spondias purpurea L. using male and female Swiss albino mice. To determine the protective effects of the extract, benzo[a]pyrene (B[a]P) and cyclophosphamide (CP) were selected as cell damage inducers. The extract was examined at doses of 500, 1000, or 1500 mg/kg body weight (BW)via gavage alone or concomitant with B[a]P or CP. Oxidative stress was measured by quantification of blood catalase activity (CAT), reduced glutathione (GSH) levels in total blood, liver, and kidney, and concentrations of malondiadehyde (MDA) in liver and kidney. Genotoxicity and antigenotoxicity were evaluated by the comet assay using peripheral blood. Cytotoxicity, mutagenicity, and antimutagenicity were determined utilizing the micronucleus test in bone marrow and peripheral blood. The S. purpurea L extract increased CAT activity and GSH levels accompanied by a decrease in MDA levels after treatment with B[a]P and CP. No genotoxic, cytotoxic, or mutagenic effects were found in mice exposed only to the extract. These results indicate that the extract of S. purpurea exhibited protective effects against oxidative and DNA damage induced by B[a]P and CP. [ABSTRACT FROM AUTHOR]

Melanoma, an aggressive skin cancer originating from melanocytes, can metastasize to the lungs, liver, cortex, femur, and spinal cord, ultimately resulting in DNA mutagenic effects. Melatonin is an endogenous hormone and free radical scavenger that possesses the ability to protect the DNA and to exert anti-proliferative effects in melanoma cells. The aim of this study was to evaluate the effects of B16F10 melanoma cells and the effects of melatonin supplementation on genotoxic parameters in murine melanoma models. Thirty-two male C57Bl/6 mice were divided in the following four groups: PBS + vehicle (n = 6), melanoma + vehicle (n = 10), PBS + melatonin (n = 6), and melanoma + melatonin (n = 10). The melanoma groups received a B16F10 cell injection, and melatonin was administered during 60 days. After treatment, tumor sizes were evaluated. DNA damage within the peripheral blood, lungs, liver, cortex, and spinal cord was determined using comet assay, and the mutagenicity within the bone marrow was determined using the micronucleus test. B16F10 cells effectively induced DNA damage in all tissues, and melatonin supplementation decreased DNA damage in the blood, liver, cortex, and spinal cord. This hormone exerts anti-tumor activity via its anti-proliferative, antioxidative, and pro-apoptotic effects. As this result was not observed within the lungs, we hypothesized that melatonin can induce apoptosis in cancer cells, and this was not evaluated by comet assay. This study provides evidence that melatonin can reduce the genotoxicity and mutagenicity caused by B16F10 cells. [ABSTRACT FROM AUTHOR]

The present study has been carried out in Clarias batrachus to evaluate the genotoxic effect of herbicide pretilachlor using micronucleus test and comet assay. Fish were exposed to sub-lethal concentrations of pretilachlor (0.29 − 0.58 mg/L) – for 30 to 60 d. Micronucleus test and comet assay of erythrocytes revealed that genetic damage increases with increasing concentration of the herbicide at all durations of exposure. Maximum genetic damage was observed at day 30 after which it decreases and becomes minimum at day 60. [ABSTRACT FROM AUTHOR]

Schistosomiasis is considered a neglected disease, but it is the cause of many social and economic problems in many developing countries. The aim of the present study was to find an alternative molluscicide of botanical origin to decrease the spread of this disease. The investigation studied the effect of the methanolic extract of Colchicum ritchii flowers on Biomphalaria alexandrina snails, larvae of Schistosoma mansoni, and the freshwater cladoceran Daphnia magna. The preliminary phytochemical screening test confirmed the presence of tannins and saponins that might be responsible for cytotoxic effects. The methanolic extract had a molluscicidal activity on B. alexandrina snails with an LC50 of 35.1 mg L−1 after 24 h of exposure. The LC50 of D. magna after 24 h was 63.5 mg L−1. The extract also had a larvicidal activity and caused alterations in the haemocytes of B. alexandrina snails. Aggregations of both hyalinocytes and granulocytes were formed after exposure for 24 h to LC25. Both the mean number of micronuclei per slide and the olive tail moment of snails exposed to LC10 and LC25 of the extract were increased compared to control snails. In conclusion, C. ritchii extract potentially could be used as a molluscicide and larvicide. [ABSTRACT FROM AUTHOR]

Nerol (cis-3,7-dimethyl-2,6-octadien-1-ol) is a monoterpene widely used in cosmetic products, household detergents and cleaners, as well as a flavoring in several food products. Despite the high level of human exposure to nerol, an absence of studies regarding potential genetic toxicity in human cells exists. The aim of this investigation was to examine the cytotoxic and genotoxic potential of this monoterpene on human peripheral blood mononuclear cells as well as hepatic metabolizing HepG2/C3A human cell line. Cytotoxicity was assessed using trypan blue staining and MTT assay while genotoxicity was determined utilizing the comet and micronucleus test. Cytotoxicity tests showed cell viability greater than 70% for concentrations between 2.5 and 500 µg/ml. Both cell types exhibited significant DNA damage and chromosomal mutations after medium and high concentration incubation with nerol indicating that the safety of use of this monoterpene in various formulations to which humans are exposed needs to be monitored and requires more comprehensive investigations. [ABSTRACT FROM AUTHOR]

Azathioprine (Aza) is a purine antimetabolite immunosuppressant that is widely employed for immunosuppressive therapy in post-transplant recipients or patients with autoimmune diseases. Chronic use of immunosuppressants might produce several side effects, including a high rate of neoplasms in these patients. Considering that genotoxic effects are associated with an increased risk of developing cancer, the aim of this study was to examine the recombinogenic, genotoxic, and cytotoxic effects of Aza using Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster, as well as comet and micronucleus assays in mouse bone marrow cells. Further, the adverse effects of Aza were determined in mouse hepatic and renal tissues using histopathological analysis. Data demonstrated that Aza induced significant increased genotoxicity in D. melanogaster and mouse bone marrow cells at all concentrations tested. Homologous recombination was the predominant genotoxic event noted for the first time to be initiated by Aza in SMART. In histopathological analysis, Aza did not show any marked toxic activity in mouse hepatic and renal tissues. Therefore, the high rate of neoplasms reported in patients with long-term use of Aza may be attributed, at least partially, to the genotoxic action of this drug. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate genomic instability and cytotoxicity in buccal mucosa cells of children living in abnormal conditions from Santos Sao Vicente estuary. The study area is located between coordinates 23°58ʹ11.8"S and 46°24ʹ26.3"W, in the southwestern zone of the Sao Paulo State, Brazil. A total of 40 children was distributed into two groups: exposed and non-exposed groups. The frequency of micronuclei increased to buccal mucosa cells of children living in Santos Sao Vicente estuary when compared to the non-exposed group (p < 0.05). No remarkable differences on buccal cells were found inpyknosis, karyorrhexis and karyolysi between groups. Taken together, our results suggest that children living in contaminated areas comprise a high group for genomic instability on buccal mucosa cells. Given that the current investigation is a preliminary study, further analysis with a larger sample of children is interesting as a future perspective. [ABSTRACT FROM AUTHOR]

Citral, 3,7-dimethyl-2,6-octadien-1-al, one of the main components of the essential oils obtained from several plants, is used as a food additive and as a fragrance for detergents, cosmetics and other toiletries. The literature shows disparity regarding citral genotoxicity. Thus, the main objective of our work was to evaluate the genotoxic effects of citral in human cell cultures, HepG2 and leukocytes. Cytotoxicity assays (trypan blue and MTT) showed citral toxic effects in HepG2 cells (with metabolizing liver enzymes), which contrasted with the absence of toxicity in leukocytes. After citral exposure, both cell types did not demonstrate clastogenic/aneugenic effects in the micronucleus test. However, for the comet assay, citral exposure lead to significant genotoxic effects in both HepG2 (even to citral low concentrations) and leukocytes. The use of citral must be viewed with caution due to its ability to induce DNA damages, especially after being metabolized by cells with active liver enzymes. [ABSTRACT FROM AUTHOR]

Chalcones are chemically defined as α,β–unsaturated ketones with a 1,3-diphenyl-2-propen-1-one nucleus. These compounds occur naturally in plants and are considered precursors of flavonoids. Given that evaluating genetic toxicology tests is essential in investigating the safe use and chemopreventive potential of different natural and synthetic compounds, this study aimed to assess the genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activity of the chalcone 1E,4E-1-(4-chlorophenyl)-5-(2,6,6-trimethylcyclohexen-1-yl)penta-1,4-dien-3-one (CAB7β). The CAB7β was synthesized via Claisen–Schmidt reaction. The Ames test was applied using the co-treatment model as well as a micronucleus assay of mouse bone marrow with co-, pre- and post-treatment models. Our results indicate no genotoxic effect for CAB7β in any of the tests applied. At all the concentrations used, CAB7β showed a significant DNA protective effect against the mutagenic action of 4-nitroquinoline-1-oxide and sodium azide according to the Ames test, and against doxorubicin in the co-, pre- and post-treatment models of the micronucleus assay. CAB7β alone displayed cytotoxic activity in the micronucleus test. At concentrations of 12,5 and 50 µg/plate, CAB7β showed a moderate cytotoxic profile only in Salmonella typhimurium strain TA98. However, an anticytotoxic effect was observed against S. typhimurium strain TA100 for all the concentrations tested and during co-, pre- and post-treatment in the micronucleus assay. It was concluded that CAB7β exhibited a slightly cytotoxic effect in S. typhimurium strain TA98 and significant antigenotoxic and anticytotoxic effects in cells of mouse, making it a promising candidate in chemoprevention and possibly in the development of new cancer treatments. [ABSTRACT FROM AUTHOR]

Triflumuron (TFM) is an insect growth regulator (IGR), an insecticide commonly used over the world. It is known for its several toxic manifestations, such as reprotoxicity, immunotoxicity and hematotoxicity, which could affect public health. However, studies that reveal its toxic effects on mammalians are limited. To reach this purpose, our study aimed to elucidate the eventual genotoxic effects of TFM in mice bone marrow cells and in HCT 116 cells after a short term exposition. TFM was administered intraperitoneally to Balb/C male mice at doses of 250, 350 and 500 mg/kg bw for 24 h. Genotoxicity was monitored in bone marrow cells using the comet test, the micronucleus test and the chromosome aberration assay. Our results showed that TFM induced DNA damages in a dose-dependent manner. This genotoxicity was confirmed also in vitro on human intestinal cells HCT 116 using the comet test. It was then asked whether this genotoxicity induced by TFM could be due to an oxidative stress. Thus, we found that TFM significantly decreased HCT 116 cell viability. In addition, it induced the generation of reactive oxygen species (ROS) followed by lipid peroxidation as revealed by the increase in the malondialdehyde (MDA) levels. Similarly, the activation of the antioxidant enzymes (catalase and superoxide dismutase) was also observed. Our results indicated that, in our experimental conditions, TFM had a genotoxic effect on bone morrow cells and in HCT 116 cells. Moreover, we demonstrated that this genotoxicity passes through an oxidative stress. [ABSTRACT FROM AUTHOR]

Among neonicotinoid insecticides, the fastest growing class of insecticides worldwide over the past decade, imidacloprid (IMI) is the most widely used one. The effects of IMI on human health, especially on genetic toxicity have gradually aroused more attention. In this study, a combined in vitro approach employing the thymidine kinase (TK) gene mutation assay, the comet assay and the micronucleus test was taken to assess the genotoxicity of IMI. The mechanism behind IMI was also explored by measuring reactive oxygen species (ROS) in the human lymphoblastoid TK6 cells. The cells were treated with 0.01, 0.1, 1, 5, and 10 μg/mL IMI, and ROS generation was measured by the use of 2,7,-dichlorofluorescin diacetate (DCFH-DA) assay. IMI significantly increased the micronucleus (MN) frequency, TK mutations and DNA damage with a dose-effect relationship, and the lowest effective concentration in those tests was 0.1 μg/mL. However, no obvious change of intracellular ROS was observed for any concentrations. The results indicate that IMI has potential genotoxic effects on TK6 cells, but ROS does not seem to be involved as a mechanism of genotoxicity under the experimental conditions. [ABSTRACT FROM AUTHOR]

The use of natural products from herbs may be a therapeutic option in dyslipidemia treatment. Campomanesia xanthocarpa (Mart.) O. Berg (Myrtaceae) leaves have been used to decrease cholesterol levels. However, studies to determine activities of this plant on triglycerides metabolism have received little attention. The aim of this study was to examine anti-hyperlipidemic effects of a C. xanthocarpa aqueous leaf extract (CxAE) and assess protective actions against oxidative stress and DNA damage. The tyloxapol-induced hyperlipidemia model was used in Wistar rats. Rats were treated orally with CxAE either 250 or 500 mg/kg/day for 7 days prior to tyloxapol administration. Biochemical parameters, oxidative stress levels, and genomic instability were assessed in several tissues. CxAE decreased cholesterol and triglyceride levels in serum and hepatic and renal DNA damage in tyloxapol-treated rats. There was no marked effect on the micronucleus frequency in bone marrow. The extract increased catalase activity and decreased glutathione S-transferase activity in kidney tissue. CxAE showed anti-hyperlipidemic effects, improved oxidative parameters, and protected DNA against damage induced by tyloxapol-induced hyperlipidemia, suggesting C. xanthocarpa leaves may be useful in preventing dyslipidemias. Abbreviations: ALP: Alkaline phosphatase; ALT: Aspartate aminotransferase; ANOVA: Analysis of variance; AST: Aspartate aminotransferase; Ator: Atorvastatin; CAT: Catalase; Chol: Cholesterol; CxAE: Campomanesia xanthocarpa aqueous extract; GST: Glutathione S-transferase; HDL: High density cholesterol; i.p.: Intraperitoneal; NCE: Normochromatic erythrocyte; PBS: Phosphate buffer solution; PCE: Polychromatic erythrocyte; ROS: Reactive oxygen species; SD: Standard deviation; SOD: Superoxide dismutase; T: Tyloxapol; TBARS: Thiobarbituric acid reacting substances; TG: Triglyceride [ABSTRACT FROM AUTHOR]

Myrciaria dubia is a native plant from the Amazon region which produces red-purplish fruit rich in antioxidant compounds such as ascorbic acid, carotenoids, and phenolic. M. dubia fruit is used to prepare juices considered to possess high nutritional content providing health benefits. The aim of this study was to examine the ability of M. dubia juice to protect DNA against genomic instability induced by sub-acute ethanol consumption attributed to oxidative stress. Mice were treated for 28 days with juice at 25% and 50% diluted in distilled water or with the diluted combination juice plus ethanol (5 g/kg). The genotoxic/antigenotoxic and mutagenic/antimutagenic effects were assessed using comet assay in blood, liver, and kidney and micronucleus (MN) test with bone marrow. In addition, the mutagenicity was also evaluated using Salmonella/microsome assay. Phytochemical compounds were determined using HPLC/PDA/MS/MS. The juice did not induce genotoxic effects in blood, kidney, and liver cells at both doses. In combination with ethanol, the juice reduced the alcohol-mediated DNA damage in all tissues analyzed. Further, the juice did not produce mutagenic effects and decreased mutagenicity induced by ethanol in the bone marrow. The anthocyanins were major compounds detected by HPLC/PDA/MS/MS, which modulated genotoxic and mutagenic effects initiated by ethanol and at least in part appeared responsible for the observed antigenotoxic and antimutagenic effects of M. dubia juice. [ABSTRACT FROM AUTHOR]

Acetamiprid (ACE), a neonicotinoid insecticide, is widely used in agriculture either alone or in combination with other insecticides. A combined approach employing micronucleus test (MNT) and chromosomal aberrations (CA) assay was utilized to assess the genotoxic effects of ACE in bone marrow of Swiss albino male mice. Acetamiprid was administered i.p. daily at 4.6 and 2.3 mg/kg/day along with 3% gum acacia as negative control for 60 and 90 days and cyclophosphamide (50 mg/kg b.wt.) as positive control. ACE treatment resulted in a dose-dependent increase in the frequencies of micronuclei per cell and chromosomal aberrations in bone marrow cells. The increased micronuclei formation in total erythrocyte cells (immature PCEs and mature NCEs) was observed only at higher dose level (4.6 mg/kg b.wt.) administered for 90 days. The test also indicated the cytotoxic effect of higher dose level of pesticide by PCE/NCE ratio. The number of chromosomal aberrations were increased in the pesticide treated group compared to the negative control group, although significant increase was observed only in the group exposed to higher dose level of pesticide for both 60 and 90 days. Thus, daily exposure of ACE at a dose level of 4.6 mg/kg body weight for 60 and 90 days caused genotoxic and cytotoxic effects on the somatic cells of Swiss albino male mice. [ABSTRACT FROM AUTHOR]

Beta-myrcene [or myrcene (1,6-Octadiene, 7-methyl-3-methylene-)] and the essential oils containing this monoterpene have been widely used in cosmetics, detergents, and soaps, and as flavoring additives for food and beverages. Due to the potentially high level of human exposure to beta-myrcene, and absence of studies involving its genotoxicity in human cells, the aim of this study was to investigate the cytotoxic and genotoxic potential of this terpenoid in non-metabolizing cells (leukocytes) and liver metabolizing cells (HepG2/C3A cells). Prior to the genotoxic assessment by the comet and micronucleus (MN) assays, a range of beta-myrcene concentrations was tested in a preliminary MTT assay. Regarding the MTT assay, the results showed cytotoxic effects for leukocytes at 250 µg/ml and higher concentrations, while for HepG2/C3A cells, absence of cytotoxicity was noted relative to all tested concentrations (after 24 hr exposure). Thus, the concentrations of 2.5, 10, 25, 50, and 100 µg/ml for leukocytes, and 2.5, 100, and 1000 µg/ml for HepG2/C3A cells were selected for subsequent assays. Genotoxicity evaluation demonstrated significant DNA damage in the comet assay and significant chromosomal abnormalities including nucleoplasmic bridges and nuclear buds in HepG2/C3A cells at beta-myrcene concentrations of 100 and 1000 µg/ml. Under our experimental conditions, caution is recommended in the use of beta-myrcene, since this compound produced genotoxic effects especially after metabolic activation using human HepG2/C3A cells, which may be associated with carcinogenic and teratogenic effects previously reported in the literature. [ABSTRACT FROM AUTHOR]

This study reports for the first time in the chemical composition of acetone, ether, ethyl acetate and dichloromethane extracts of Hypogymnia tubulosa determined by HPLC-UV, GC-FID and GC-MS as well as effect of H. tubulosa acetone extract on micronucleus distribution on human lymphocytes and on cholinesterase activity. Additionally, antioxidant (estimated via DPPH, ABTS, TRP, CUPRAC and TPC assays) and antibacterial activity against two Gram-positive and three Gram-negative bacteria were also determined. The HPLC-UV analysis revealed the presence of depsidones, 3-hydroxyphysodic, 4-O-methyl physodic acid, physodic and physodalic acid together with two depsides, atranorin and chloroatranorin. GC-FID and GC-MS analyses enabled the identification of atranol, chloroatranol, atraric acid, olivetol, olivetonide and 3-hydroxyolivetonide as the main components. The results of present study show that H. tubulosa acetone extract is a promising candidate for in vivo experiments considering antioxidant activity. [ABSTRACT FROM AUTHOR]

Crataegus oxyacantha L. (Rosaceae) is a medicinal plant with a long history of use in European, Chinese, and American. The majority of pharmacological activities associated with fruit extracts of C. oxyacantha L. are related to cardio-stimulant properties utilized in the treatment of atherosclerosis, hypertension with myocardic insufficiency, angina pectoris, cardiac rhythm alterations, and heart failure. Some other therapeutic uses for renal calculi, dyspnea, as well as a diuretic, sedative, and anxiolytic were also reported. Due to the beneficial potential of C. oxyacantha fruits extract but evidence in vitro of genetic toxicity, the aim of the present study was to examine the genotoxic potential of plant extract in vivo in mice. The extract was administered orally, daily by gavage at doses of 50, 100, and 200 mg/kg body weight for seven days. Data demonstrated that C. oxyacantha extract did not markedly induce DNA damage in leukocytes and bone marrow cells by the comet assay; however, the extract produced a significant rise in micronucleated polychromatic erythrocytes (PCE) at all tested doses in a non-dose dependent manner as evidenced by the micronucleus test. The PCE/normochromatic erythrocytes (NCE) ratio indicated no significant cytotoxicity. Under our experimental conditions, C. oxyacantha fruits extract exhibited weak clastogenic and/or aneugenic effects in bone marrow cells of male mice, confirming our previous in vitro findings that this plant extract induced genotoxicity suggesting that prolonged or high dose use needs to be undertaken with caution. [ABSTRACT FROM AUTHOR]

In view of the biological activities and growing therapeutic interest in oleoresin obtained from Copaifera multijuga, this study aimed to determine the genotoxic and antigenotoxic potential of this oleoresin (CMO) and its chemical marker, diterpene (-)-copalic acid (CA). The micronucleus (MN) assay in V79 cell cultures and the Ames test were used for in vitro analyses, as well as MN and comet assays in Swiss mice for in vivo analyses. The in vitro genotoxicity/mutagenicity results showed that either CMO (30,60, or 120 µg/ml-MN assay; 0.39-3.12 mg/plate-Ames test) or CA (2.42; 4.84, or 9.7 µg/ml-MN assay; 0.39-3.12 mg/plate-Ames test) did not induce a significant effect on the frequency of MN and number of revertants, demonstrating an absence of genotoxic and mutagenic activities, respectively, in vitro. In contrast, these natural products significantly reduced the frequency of MN induced by methyl metha- nesulfonate (MMS), and exerted a marked inhibitory effect against indirect-acting mutagens in the Ames test. In the in vivo test system, animals treated with CMO (6.25 mg/kg b.w.) exhibited a significant decrease in rate of MN occurrence compared to those treated only with MMS. An antigenotoxic effect of CA was noted in the MN test (1 and 2 mg/kg b.w.) and the comet assay (0.5 mg/kg b.w.). Data suggest that the chemical marker of the genus Copaifera, CA, may partially be responsible for the observed chemopreventive effect attributed to CMO exposure. [ABSTRACT FROM AUTHOR]

Chlorpyrifos is a commonly used organophosphate insecticide that causes toxicological effects in aquatic organisms especially in fish. This study determined the effects of chlorpyrifos on the genotoxic and hematological parameters of freshwater fish,Labeo rohita. The genotoxic effects of different sublethal concentrations of chlorpyrifos were investigated in the erythrocytes ofLabeo rohita(commonly known as Rohu) using the Micronucleus test. Effects of chlorpyrifos on the hematological parameters of the fish were also observed. Fish specimens were exposed to three sublethal concentrations of chlorpyrifos viz., sublethal I (SL-I, 1/6th of LC50 = ∼73.8 μg/L), sublethal II (SL-II, 1/4th of LC50 = ∼110.7 μg/L) and sublethal III (SL-III, 1/2nd of LC50 = ∼221.4 μg/L) for 96 h. Blood samples were collected at every 24 h and were subjected to the Micronucleus assay. The observed micronucleus frequencies were concentration and time-dependent. The MN induction was significantly highest (p < 0.01) at all the concentrations on 96-h exposure. During the experimental period, hematological parameters like total erythrocytes count (TEC), hemoglobin (Hb) and packed cell volume (PCV) decreased, whereas total leukocytes count (TLC) increased. This study indicated that the Micronucleus assay is a useful tool to detect genotoxic potential of chlorpyrifos in fish. [ABSTRACT FROM AUTHOR]

Formaldehyde (FA) is a mutagenic chemical – a property mitigatedin vivoby rapid detoxification and limited tissue distribution following inhalation of the free agent. Endogenously produced FA is necessary for life and required for one-carbon transfer reactions; however, FA derived from external sources (exogenous FA), which may be in the form of methanol, may increasein vivoconcentrations above naturally occurring physiological levels. Both endogenous and exogenous FA produce DNA monoadducts, DNA–DNA and DNA–protein cross-links (DDX and DPX) but, when exposed to exogenously-derived free FA, DNA monoadducts, DDX, and DPX are only produced at initial sites of contact. In contrast, methanol may systemically induce DNA adducts distally. FA also induces oxidative stress/lipid peroxidation with some individuals suggesting the resulting reactive aldehydes may have the potential to induce distal site DNA damage with the resulting reactive aldehydes having the potential to induce distal site DNA damage. Chromosome changes in the form of aberrations or micronuclei in blood cells have been studied in FA-exposed animals and humans, with most of the former being negative. Human occupational studies have given mixed results for such changes in peripheral blood lymphocytes (PBLs) which circulate widely but do not reflect recent bone marrow (BM) events. Recent studies reporting changes in human BM or hematopoietic precursor cells (HPCs) either have had confounding exposures or could not distinguishin vivofromin vitrooccurrences. The reported genetic changes in circulating blood cells do not provide convincing support for FA’s classification as a human leukemogen. [ABSTRACT FROM PUBLISHER]

The genotoxic potential of hexachlorocyclohexane (HCH) isomers (α-, β-, and γ-) which are organochlorine pesticides was tested in peripheral blood lymphocyte cultures from two donors by using the cytokinesis-block micronucleus assay. Micronucleus (MN) frequency, binucleated cells with micronucleus (BNMN), and cytokinesis-blocked proliferation index (CBPI) were determined as genotoxic and cytotoxic endpoints. At the concentration ranges tested (12.5–100 μg.L −1), all HCH isomers induced dose-dependent cytotoxic effects, γ-HCH being the most toxic. This isomer was also able to induce significant increase in MN frequency and BNMN cells indicating a genotoxic potential at 50 and 100 μg.L −1. The genotoxic test of β-HCH showed a positive induction of MN and BNMN cells at the highest concentration of 100 μg.L −1and a significant cytotoxicity at 50 μg.L −1. Under the experimental condition used, α-HCH was unable to induce any significant increase in MN frequency confirming that α-HCH is a non-genotoxic agent. [ABSTRACT FROM PUBLISHER]

FR-900098 is an inhibitor of 1-deoxy-d-xylulose-5-phosphate (DXP) reductoisomerase, the second enzyme in the non-mevalonate isoprenoid biosynthesis pathway. In previous studies, FR-900098 was shown to possess potent antimalarial activityin vitroand in a murine malaria model. In order to provide a basis for further preclinical and clinical development, we studied the acute toxicity and genotoxicity of FR-900098. We observed no acute toxicity in rats, i.e. there were no clinical signs of toxicity and no substance-related deaths after the administration of a single dose of 3000 mg/kg body weight orally or 400 mg/kg body weight intravenously. No mutagenic potential was detected in theSalmonella typhimuriumreverse mutation assay (Ames test) or anin vitromammalian cell gene mutation test using mouse lymphoma L5178Y/TK+/−cells (clone 3.7.2C), both with and without metabolic activation. In addition, FR-900098 demonstrated no clastogenic or aneugenic capability or significant adverse effects on blood formation in anin vivomicronucleus test with bone marrow erythrocytes from NMRI mice. We conclude that FR-900098 lacks acute toxicity and genotoxicity, supporting its further development as an antimalarial drug. [ABSTRACT FROM PUBLISHER]

Our group already demonstrated that europium hydroxide nanorods (EHNs) show none or mild toxicity in C57BL/6 mice even at high dose and exhibited excellent pro-angiogenic activity towardsin vitroandin vivomodels. In the present study, we evaluated thein vivocytogenetic toxicity of intraperitoneally administered EHNs (12.5–250 mg/kg/b.w.) in male and female Swiss albino mice by analyzing chromosomal aberrations (CAs), mitotic index (MI), micronucleus (MN) from bone marrow and peripheral blood. Furthermore, we performed the cytogenetic toxicity study of EHNs towards Chinese hamster ovary (CHO) cells, in order to compare with thein vivoresults. The results of CA assay of mice treated with EHNs (12.5–125 mg/kg/b.w.) showed no significant change in the formation of aberrant metaphases compared to the control group. Also, there was no significant difference in the number of dividing cells between the control group and EHNs-treated groups observed by MI study, suggesting the non-cytotoxicity of EHNs. Additionally, FACS study revealed that EHNs do not arrest cells at any phase of cell cycle in the mouse model. Furthermore, MN test of both bone marrow and peripheral blood showed no significant differences in the induction of MNs when compared with the control group.In vitroresults from CHO cells also support ourin vivoobservations. Considering the role of angiogenesis by EHNs and the absence of its genotoxicity in mouse model, we strongly believe the future application of EHNs in treating various diseases, where angiogenesis plays an important role such as cardiovascular diseases, ischemic diseases and wound healing. [ABSTRACT FROM AUTHOR]

Isoflavones are phytoestrogens reported to be potent antioxidant agents. In contrast, the antileishmanial meglumine antimoniate has mutagenic activities. This study evaluated the ability of soy isoflavones to reduce DNA damage induced by meglumine antimoniate. Antimutagenic effects (by micronucleus test) were tested using Swiss mice divided into seven groups treated with meglumine antimoniate(425 mg/kg bw pentavalent antimony); cyclophosphamide (50 mg/kg bw); water (negative control); single isoflavones dose (1.6 mg/kg bw), and three groups received one dose of isoflavones via gavage (0.4 mg/kg bw, 0.8 mg/kg bw or 1.6 mg/kg bw) plus meglumine antimoniate via intraperitoneal, simultaneously. To evaluate antigenotoxicity (by Comet assay), each group with 10 animals received the above-mentioned control doses; single dose of isoflavones 0.8 mg/kg bw, and three groups received isoflavones (0.8 mg/kg bw) by gavage along with intraperitoneal meglumine antimoniate, which were treated with isoflavones 24 h before or after receiving meglumine antimoniate (pre-treatment and post-treatment, respectively) or simultaneously. Cells were harvested 24 h after the treatment, and the data were evaluated by ANOVA followed by Tukey’s test (p < 0.05). The data from the simultaneous treatment by micronucleus test revealed that isoflavones (0.4 and 0.8 mg/kg) were able to reverse the mutagenic effect of Glucantime. Moreover, all regimes of the treatment with 0.8 mg/kg bw dose were able to reduce the genotoxicity caused by meglumine antimoniate. It is suggested that the protective effect of isoflavones against DNA damage is related to their ability to reduce oxidative stress caused by the trivalent Sb(III) metabolite of meglumine antimoniate. [ABSTRACT FROM PUBLISHER]

Benzo(a)pyrene (B(a)P) is a commonly used indicator for polycyclic aromatic hydrocarbons (PAHs) contamination. The use of certain phytochemicals and some polyphenolic compounds proved to be effective in blocking PAH-induced effects. The aim of the present study was to examine the possible inhibitory effects of ellagic acid (EA), present in berries and nuts, against B(a)P-mediated toxicity usingin vitroandin vivotest systems.In vitromethod included the Ames test, usingSalmonella typhimuriumtester strain TA100.In vivoexperiments were based on mouse bone marrow micronucleus (MN) assay and immunoblotting. EA produced a decrease in the number of revertant colonies against B(a)P in the Ames assay. Further, there was a reduction in the mean number of micronucleated polychromatic erythrocytes in the presence of EA in the co-treatment protocol of the MN test. Western blotting results showed downregulation of CYP450 isoform CYP1A1 which prevented bioactivation of B(a)P. Thus, the present study demonstrates antimutagenic role played by EA against the mutagenic activity of B(a)P in bothin vitroandin vivosystems. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the individual radiosensitivity of the human genome in long-term residents of areas with high radon concentration. Materials and methods: The materials used for this investigation were venous blood samples extracted from children living in the boarding school of Tashtagol (Kemerovo Region, Russia). Cytogenetic damage assessment was performed using the cytokinesis-block micronucleus assay (CBMN) on peripheral blood lymphocytes. PCR, gel electrophoresis and product detection using a transilluminator were used to determine polymorphisms in the genes ADPRT (rs 1136410), h OGG1 (rs 1052133), NBS1 (rs 1805794), XRCC1 (rs 25487), XpC (rs 2228001), XpD (rs 13181), and XpG (rs 17655). Statistical analysis was performed using nonparametric methods. To ensure accurate results, FDR-correction for multiple comparisons was performed. Results: We discovered a significant increase in the frequency of binucleated lymphocytes with micronuclei (MN) in carriers of the His/His genotype of the XpG gene Asp1104His polymorphism in comparison to heterozygous and homozygous carriers of the Asp allele. In addition, the Ala/Ala genotype for the ADPRT gene Val762Ala polymorphism and the Glu/Gln genotype for the NBS1 gene Glu185Gln polymorphism were associated with the elevated frequency of binucleated lymphocytes with nucleoplasmic bridges (NPB). Conclusions: As a result of this study, the elevated frequency of cytogenetic damage in people with particular DNA-repair gene polymorphisms in response to chronic exposure to radon was demonstrated. It was shown that the genes and corresponding polymorphisms (the XpG gene Asp1104His polymorphism, the ADPRT gene Val762Ala polymorphism and the NBS1 gene Glu185Gln polymorphism) can be used as molecular genetic markers of increased individual radiosensitivity in long-term residents of areas with high concentrations of radon. [ABSTRACT FROM AUTHOR]

The cytogenotoxicity and histopathological alterations induced by xenobiotics in Lekki Lagoon and Ogun River onSynodontis clariaswere investigated. Fish from these water bodies and a fish farm (control) were examined for micronucleated, binucleated, and immature erythrocytes in both gill and peripheral blood. Also gill, liver, kidney, and ovary were processed for histopathology using hematoxylin-eosin staining. Concentrations of cadmium, zinc, lead and copper in the water were determined. There was significant (p< 0.05) increase in micronucleated, binucleated, and immature erythrocytes in both gill and peripheral blood ofS.clariasfrom the lagoon and river compared to the reference site. Loss and disorganization of the primary and secondary lamellae, multifocal degeneration, hemorrhages, cellular infiltration, congestions, vacuolations, atresia, and necrosis were common lesions in the examined tissues of fish from the lagoon and river. Cd, Zn, Pb, and Cu in water samples from the lagoon and river were higher than the reference site. Xenobiotics in Lekki Lagoon and Ogun River, mostly metals, induced deoxyribonucleic acid (DNA) and pathological damage inS. clarias. [ABSTRACT FROM AUTHOR]

Methylthiophanate is one of the widely used fungicides to control important fungal diseases of crops. The aim of this study was to elucidate the short-term hematoxicity and genotoxicity effects of methylthiophanate administered by intraperitoneal way at three doses (300, 500 and 700 mg/kg of body weight) after 24, 48 and 72 h. Our results showed, 24 h after methylthiophanate injection, a hematological perturbation such as red blood cells ( p < 0.05, p < 0.05 and p < 0.01) and hemoglobin content ( p < 0.05), respectively, and a noticeable genotoxic effect in WBC evidenced by a significant increase in the frequency of the micronuclei and a decrease in cell viability. An increase in erythrocyte osmotic fragility was also noted after 24 and 48 h of methylthiophanate treatment at graded doses. A significant increase in hydrogen peroxide, advanced oxidation of protein products and malondialdehyde levels, in erythrocytes of methylthiophanate-treated rats with 300, 500 and 700 mg/kg of body weight, was also observed after 24 h of treatment ( p < 0.05, p < 0.01 and p < 0.001, respectively), suggesting the implication of oxidative stress in its toxicity. Antioxidants activities of superoxide dismutase and glutathione peroxidase in erythrocytes significantly increased ( p < 0.001) 24 h after the highest dose injected. While all these parameters were improved after 72 h of methylthiophanate injection (300, 500 and 700 mg/kg body weight). In conclusion, these data showed that the exposure of adult rats to methylthiophanate resulted in oxidative stress leading to hematotoxicity and the impairment of defence system, confirming the pro-oxidant and genotoxic effects of this fungicide. [ABSTRACT FROM AUTHOR]

Background and objectives: The aim of this study was to evaluate genotoxicity and mutagenicity in peripheral blood and buccal mucosal cells in mucopolysaccharidosis (MPS) I, II or VI patients. Methods: A total of 12 patients with MPS type I, II and VI attended at the Institute of Genetics and Inborn Errors of Metabolism treated with enzyme replacement therapy (ERT) and 10 healthy control volunteers were included in this study. Mechanically exfoliated cells from cheek mucosa (left and right side) were used to micronucleus test and single cell gel (comet) assay in peripheral blood cells. Results: The results of this study detected the presence of genetic damage in peripheral blood for all individuals with MPS treated with ERT, regardless of type of MPS as depicted by tail moment results. In addition, an increased number of micronucleated cells were found in buccal cells of MPS type II patients. It was also observed an increase of other nuclear alterations closely related to cytotoxicity as depicted by the frequency of pyknosis, karyolysis and karyorrhexis in buccal mucosa cells of MPS VI patients ( p < 0.05). Conclusion: Taken together, such results demonstrate that metabolic alterations induced by the enzymatic deficiency characteristic of MPS associated with ERT therapy can induce genotoxicity and mutagenicity in peripheral blood and buccal mucosa cells, respectively. This effect appears to be more pronounced to MPS II. [ABSTRACT FROM AUTHOR]

The genotoxic effects of commonly used agricultural pesticides viz., carbosulfan, glyphosate, and atrazine, were evaluated in Channa punctatus (Pisces, Perciformes) using micronucleus (MN) test and induction of nuclear lesions (NL). The 96 h LC50 value were estimated by probit analysis as 0.27, 32.0 and 42.0 mg L−1, respectively, for carbosulfan, glyphosate, and atrazine using semi-static bioassays. Based on these values, three sublethal test concentrations of carbosulfan (0.07, 0.13, 0.20 mg L−1), glyphosate (8.1, 16.3, 24.4 mg L−1) and atrazine (10.6, 21.2, 31.8 mg L−1) corresponding to ¼, ½ and ¾ of the LC50 of the pesticides respectively, were selected for exposure for 96 h. Peripheral blood samplings were taken at intervals of 24 h for assessment of MN and NL frequencies. Considerably higher genotoxic damage was induced by carbosulfan as compared to glyphosate and atrazine. There were significant effects ( p < 0.01) of concentrations in all the treated groups. The induction of MN and NL was highest at 96 h pesticide exposure at all test concentrations. The nuclear abnormalities recorded in this study, such as blebbed-, lobed-, notched- and bi-nuclei, other than micronuclei, are indicators of genotoxic damage. [ABSTRACT FROM AUTHOR]

Fish have been shown to act as sentinel organisms in genetic toxicology studies and the micronucleus (MN) test using fish erythrocytes has been successfully used to evaluate the genotoxic impact of environmental pollutants on aquatic environments. This study used the MN test of peripheral blood of specimens of a native fish species (Hyphessobrycon luetkenii) to evaluate the genotoxicity of the water of two unconnected reservoirs of the Canela National Forest in southern Brazil. Fish were caught in the reservoirs and MN frequencies in blood smears were determined. Baseline MN frequency ofH. luetkeniiwas determined in the uncontaminated reservoir (reference site) and compared with the results obtained at two different sampling periods (winter and spring) in the reservoir which receives discharges of industrial and municipal wastes. In the spring season, MN frequency in the contaminated reservoir was about five times higher than in the reference site (0.51‰ and 0.10‰, respectively). The results of this study indicate that some fish populations are at risk of exposure to genotoxic pollutants in the Canela National Forest. [ABSTRACT FROM AUTHOR]

Roupala montana Aubl. (Proteaceae) is a typical savannah species and native to tropical South America that has a moderate mortality for adult forms of Schistossoma mansoni. Because this species has been little studied, the aim of this investigation was to evaluate the influence of R. montana extract on DNA damage induced by methyl methanesulfonate (MMS) in peripheral blood cells and liver of Swiss mice using the micronucleus and comet assay, respectively. R. montana dichloromethane extract was prepared from a stock solution (0.5 mg/mL) in 5% dimethyl sulfoxide in water. Animals received a single dose of different concentrations of R. montana (5, 10 and 20 mg/kg body weight) by gavage (0.5 mL/animal). For antigenotoxicity assessment, different concentrations of R. montana were administered simultaneously with MMS diluted in water (40 mg/kg, intraperitoneally; 0.3 mL/animal). Peripheral blood and hepatocyte samples were obtained 48 and 24 h after treatment, respectively. Results showed that R. montana administered alone indicated the absence of genotoxicity in the mouse micronucleus or comet assay. On the other hand, administration of different doses of R. montana concomitantly with MMS led to a significant reduction in frequency of micronucleated polychromatic erythrocytes and DNA damage, when compared to the group treated only with MMS. Further, for the micronucleus assay, the gradual increase of R. montana concentration led to a proportional increase in the reduction of genotoxicity induced by MMS, indicating a dose-response relationship. [ABSTRACT FROM AUTHOR]

Pesticides provide considerable protection against pest population; however, rampant accumulation of these chemicals into varied habitats across the globe necessitates the need for a careful screening of each chemical due to toxic manifestations. In the current study, the genotoxic potential of two different classes of commercial insecticides – chlorpyrifos and cypermethrin combination and Spinosad, a naturalyte were compared. Rhode Island Red chick embryos were exposed to different doses of either of these insecticides individually, byin ovotreatment. Genotoxicity was then evaluated through micronucleus (MN) test and Comet assay. The combination insecticide exposure at low doses of 0.05 and 0.1 μg/egg induced DNA damage as evidenced by an increased tail moment in the Comet assay. Further, the presence of micronucleated erythrocytes and also various abnormal cells including dacryocytes, microcytes, erythroplastids, squashed/notched nuclei, and spindle-shaped erythrocytes in the blood smear consolidates indicate the presence of insecticide-induced genotoxicity. Spinosad, however, was found only mildly genotoxic but at a high dose of 1.5 mg/egg. The results indicate that usage of naturalyte insecticide may be a better option to minimize the harmful effects of chemical insecticides. [ABSTRACT FROM AUTHOR]

The aim of the present study was to comparatively evaluate genomic damage (micronucleus) and cellular death (pyknosis, karyolysis and karyorrhexis) in exfoliated oral mucosa cells from hairdressers using two different anatomic buccal sites: cheek mucosa and lateral border of the tongue. A total of 28 hairdressers and 30 health controls (non-exposed individuals) were included in this setting. Individuals had epithelial cells from the cheek and lateral border of the tongue mechanically exfoliated, placed in fixative and dropped in clean slides that were checked for the previously mentioned nuclear phenotypes. The results pointed out statistically significant differences ( p < 0.05) of micronucleated oral mucosa cells from hairdressers in the lateral border of the tongue. Exposure to hair dyes caused an increase of other nuclear alterations closely related to cytotoxicity, such as karrhyorexis, pyknosis and karyolysis in both the oral sites evaluated. In summary, these data indicate that hairdressers are occupationally exposed to agents that are genotoxic and cytotoxic. It seems that the lateral border of the tongue is a more sensitive site to the genotoxic and cytotoxic effects of hair dyes. [ABSTRACT FROM AUTHOR]

The aim of the present study was to comparatively evaluate genomic damage and cellular death in exfoliated oral mucosa cells and peripheral blood from car painters. A total of 24 car painters and 19 healthy controls (non-exposed individuals) were included in this setting. Individuals had epithelial cells from cheek mucosa (left and right side) mechanically exfoliated, placed in fixative and dropped in clean slides which were checked for the specific nuclear phenotypes. A total of 5 μL from peripheral blood was collected for the single cell gel (comet) assay. The results pointed out statistically significant differences ( p < 0.05) of micronucleated oral mucosa cells from car painters. In addition, DNA damage was detected in peripheral blood cells by single cell gel (comet) assay. Nevertheless, exposure to car paints did not cause increases other nuclear alterations closely related to cytotoxicity such as karrhyorexis, pyknosis and karyolysis in buccal mucosa cells. In summary, the results of the present study suggest that car painters comprise a high risk group since paints can induce genotoxic and mutagenic effects in peripheral blood and oral mucosa cells, respectively. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the adverse effects of sublethal doses of fenitrothion, an organophosphothionate insecticide on brain, gill, liver, and muscle tissues as a ratio of 8-OHdG to dG to indicate the DNA damage and erythrocyte micronucleus frequency for genotoxicity of carp ( Cyprinus carpio L.) fingerlings. In our study, the mean weights and lengths of the fish ( n == 4--12) were 31.13 ±± 14.24 g and 12.53 ±± 1.41, respectively. Before the experiment, fish were maintained in aerated dechlorinated tap water at 21.8 ±± 1°°C and fed daily with commercial feed at a rate of 2% of their body weights. Experiments were conducted under static conditions in the aquaria. Technical grade (95%) fenitrothion was diluted in acetone to give a dosing solution of 10 mg/L. The increased lesions/106 DNA bases ( p < 0.05) of liver tissue of exposure group (0.49 ±± 0.18) was observed when compared to control group (0.28 ±± 0.30). There was not any significant differences between brain tissues, no damage were detectable in gill and muscle tissues of control groups, and in exposure groups altered levels of damage were detected for gill (0.06 ±± 0.05) and muscle (0.16 ±± 0.21) tissues. The increased micronucleus frequencies (%) in erythrocytes of carp following the exposure to 48 h fenitrothion (6.43 ±± 3.89; p<0.05) was observed when compared to control group (1.29 ±± 1.03). The available data indicate that there is still lack of well-established dose--response relationships between occupational or environmental exposures and the induction of 8-OHdG. Such biomarkers may be used in assessing adverse/toxic effects of pesticides as environmental stressors. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the genotoxic potential of chemicals present along the course of the river Nile using frequencies of micronuclei (MN) and nuclear lesions (NL) in erythrocytes of Nile tilapia Oreochromis niloticus niloticus and African catfish Clarias gariepinus, as biomarkers. Results showed that most of the physicochemical parameters detected and heavy metal concentrations were significantly higher in the water collected from the estuaries of the river Nile compared to other sites of the upper Nile. The frequencies of MN and NL in peripheral blood erythrocytes of Nile tilapia and African catfish were significantly higher in estuary sites in Damietta and Rosetta compared to upper sites. The lowest level of genotoxicity was observed at two sites (Aswan and Kena), considered to be less contaminated. Our results suggested that higher frequencies of MN and NL determined at Damietta and Rosetta sites may be indicative of damage produced by pollutants in these areas. The most remarkable result was that MN and NL frequencies appear to be strongly related to water quality at different sites examined, indicating that MN frequencies may serve as a reliable biomarker for testing genotoxicity in situ. The positive correlation between MN and NL induction suggested that NL may be a useful complementary assay for genotoxicity analyses when fish are used as experimental animals. It was also found that seasonal variations in MN and NL frequencies might contribute to a better understanding of genotoxic responses in the field. The use of fish as indicator organisms for monitoring the presence of genotoxic-inducing contaminants in the environment seemed justified because the effects of exposure to a complex mixture such as river water were obtained. Nile tilapia appears to be a more suitable bioindicator species than African catfish in studying genotoxic chemical pollution in the river Nile attributed to a higher sensitivity. [ABSTRACT FROM AUTHOR]