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Pseudobombax marginatum, popularly known as "embiratanha," is widely used by traditional communities as anti-inflammatory and analgesic agent. This study aimed to determine the phytochemical profile as well as cytotoxicity, acute oral toxicity, genotoxicity, and mutagenicity attributed to exposure to aqueous (AqEx) and ethanolic (EtEx) extracts of embiratanha bark. Phytochemical screening was conducted using thin-layer chromatography (TLC). Cell viability was analyzed using MTT assay with human mammary gland adenocarcinoma (MDA-MB-231) and macrophage (J774A.1) cell lines, exposed to concentrations of 12.5, 25, 50, or 100 µg/ml of either extract. For acute oral toxicity, comet assay and micronucleus (MN) tests, a single dose of 2,000 mg/kg of either extract was administered orally to Wistar rats. TLC analysis identified classes of metabolites in the extracts, including cinnamic acid derivatives, flavonoids, hydrolyzable tannins, condensed tannins, coumarins, and terpenes/steroids. In the cytotoxicity assay, the varying concentrations of extracts derived from embiratanha induced no significant alterations in the viability of MDA-MB-231 cells. The lowest concentration of EtEx significantly increased macrophage J774A.1 viability. However, the higher concentrations of AqEx markedly lowered macrophage J774A.1 viability. Animals exhibited no toxicity in the parameters analyzed in acute oral toxicity, comet assay, and MN tests. Further, EtEx promoted a significant reduction in DNA damage index and DNA damage frequency utilizing the comet assay, while the group treated with AqEx exhibited no marked differences. Thus, data demonstrated that AqEx or EtEx of embiratanha may be considered safe at a dose of 2,000 mg/kg orgally under our experimental conditions tested. [ABSTRACT FROM AUTHOR]

Familial Mediterranean Fever (FMF) is an inherited autoinflammatory disease. In this study, we aimed to assess chromosomal DNA damage and cell proliferation by using cytokinesis-block micronucleus cytome (CBMN-cyt) assay in the peripheral blood lymphocytes of untreated FMF patients carrying M694V and R202Q mutations, which are the most common MEFV gene mutations in Turkish society. The study included 20 untreated FMF patients with M694V and R202Q mutations and 20 healthy individuals of similar age and sex as the control group. Micronucleus (MN), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs) were scored in the obtained bi-nucleated (BN) cells. Additionally, the nuclear division index (NDI) was calculated using the scores of mononuclear, binuclear, and multinuclear cells. We found that MN and NPBs frequencies in FMF patients were significantly higher than in controls, and number of metaphases was significantly lower (respectively, p < 0.05, p < 0.01, and p < 0.01). However, there was no significant difference in NBUDs frequencies and NDI values between FMF patients and controls (p > 0.05). Our study is the first to evaluate FMF patients' lymphocytes using the CBMN-cyt assay, as no previous research has been found in this respect. Increased MN and NPB frequencies may be useful as biomarkers for chromosomal DNA damage, and may indicate a potential for elevated cancer risk in untreated FMF patients. [ABSTRACT FROM AUTHOR]

Commiphora myrrha, located in the tropical zone, is a widely used tree for medicinal purposes in the Arabian Peninsula and a large part of Africa. In this research, cytogenotoxic effects of the commercially available Commiphora myrrha essential oil (myrrh) were studied using micronucleus (MN), comet, and total oxidant (TOS), and total antioxidant (TAS) assays on human peripheral lymphocytes under in vitro conditions. In addition, pure pBR322 plasmid DNA was used to investigate DNA damaging/protecting activity of the essential oil. Finally, a bacterial reversion (Ames) test was performed using Salmonella typhimurium mutant strains TA98 and TA100 to determine the potential effect of the agent in the induction of gene mutations. The high concentration of Commiphora myrrha (0.125 µL/mL) induced MN formation significantly compared to the untreated control in both treatment times (24 or 48 h). Only at the highest concentration, nuclear division index (NDI) values were found lower than the controls. In the Comet test performed on healthy lymphocytes, only the highest concentration of myrrh caused significant increases in the percentage of damaged cells and genetic damage index (GDI) values. Myrrh oil showed no significant mutagenic effect on mutant Salmonella strains. In addition, the substance did not directly damage plasmid DNA but also protected DNA against damaging factors such as H2O2 and UV. Finally, in the TAS and TOS assays, no significant differences on the oxidative stress parameters were found in cell culture compared to the control. The results of this study showed that myrrh oil exerts cytogenotoxic risk only at higher concentrations. [ABSTRACT FROM AUTHOR]

Genotoxic and cytotoxic effects of Bee venom (BV) as an attempt to uncover side effects of this natural antibiotic using the following biomarkers, Micronucleus in polychromatic erythrocytes (PCEs) and chromosomal aberration in bone marrow cells. White mice have been used as experimental model for the doses (BV sting 1, BV sting 2, 75 μg.kg-1, 150 μg.kg-1, 225 μg.kg-1 and use MTC as positive control) of cellcept. Results of the current study showed a high significant mean differences of Micronucleus number in the treated groups with the dosage 225 μg.kg-1 (126.4*± 2.45) compared to negative control group (6±2.45). Numerical chromosome aberration showed a high significant mean differences in 225 μg.kg-1 (1±0.65) compared to negative control group (0.0±0.0) also structural aberration showed a high significant mean differences in 225 μg.kg-1 with gap (34.6±2.1) compared to negative control group (5±1.58). [ABSTRACT FROM AUTHOR]

In this study, we have studied the cytotoxicity and genotoxic potency of 3 pro-oxidants; H2O2, menadione and KBrO3 in different dosing scenarios, namely acute (1-day dosing) and chronic (5-days). For this purpose, relative population doubling (RPD%) and mononucleated micronucleus (MN) test were used. TK6 cells and NH32 were employed in in vitro experiments. In the study, the total acute dose was divided into 5 days for each prooxidant chemicals by dose fractionation (1/5th per day) method. Acute dosing was compared to chronic dosing. The oxidative stress caused by the exposure of cells with pro-oxidant chemicals to the cells was determined by an optimized 2′,7′-dichlorofluorescein diacetate (DCFHDA) test method. The antioxidant levels of the cell lines were altered with buthionine sulfoxide (BSO) and N-acetyl cysteine (NAC), and the effect of antioxidant capacity on the MN formation in the cells was observed with this method. In the case of H2O2 and menadione, fractional dosing has been observed to result in lower toxicity and lower genotoxicity. But in the case of KBrO3, unlike the other 2 pro-oxidants, higher MN induction was observed with fractionated doses. DCFHDA test clearly demonstrated ROS induction with H2O2 and menadione but not with KBrO3. Unexpectedly, DCFHDA test demonstrated that KBrO3 did not cause an increase ROS levels in both acute and chronic dosing, suggesting an alternative ROS induction mechanism. It was also observed that, treatment with BSO and NAC, caused increasing and decreasing of MN fold change respectively, allowing further ROS specific mechanisms to be explored. Hence, dose fractionation expectedly caused less MN, cytotoxicity and ROS formation with H2O2 and menadione exposure, but not with KBrO3. This implies a unique mechanism of action for KBrO3 induced genotoxicity. Chronic dosing in vitro may be a valuable approach allowing better understanding of how chemicals damage DNA and pose human hazards. [ABSTRACT FROM AUTHOR]

This study was carried out in a Research laboratory in the Department of Biology, College of Science, Wasit University and was designed to evaluate the rate of micronucleus (MN) formation as a cytogenetic test and the level of protein p53 as a serological test. Etoposide (VP-16) 20 mg/kg was used to know their influence on the parameters before mentioned in the case of absence or presence of (5000 IU/ KG) from vitamin D3 at different times (1 day, 1 week, 2 weeks, 3 weeks and 4 weeks). A study reached the following results: The dose 20 mg/kg of VP-16caused a significant increase at P≤0.05 in the level of protein P53 and the rate of MN, while vitamin D3 had an inhibitory influence of chemotherapy causing a significant decrease at P≤0.05 in both of the above parameters. [ABSTRACT FROM AUTHOR]

In this study, we have studied the cytotoxicity and genotoxic potency of 3 pro-oxidants; H2O2, menadione and KBrO3 in different dosing scenarios, namely acute (1-day dosing) and chronic (5-days). For this purpose, relative population doubling (RPD%) and mononucleated micronucleus (MN) test were used. TK6 cells and NH32 were employed in in vitro experiments. In the study, the total acute dose was divided into 5 days for each prooxidant chemicals by dose fractionation (1/5th per day) method. Acute dosing was compared to chronic dosing. The oxidative stress caused by the exposure of cells with pro-oxidant chemicals to the cells was determined by an optimized 2′,7′-dichlorofluorescein diacetate (DCFHDA) test method. The antioxidant levels of the cell lines were altered with buthionine sulfoxide (BSO) and N-acetyl cysteine (NAC), and the effect of antioxidant capacity on the MN formation in the cells was observed with this method. In the case of H2O2 and menadione, fractional dosing has been observed to result in lower toxicity and lower genotoxicity. But in the case of KBrO3, unlike the other 2 pro-oxidants, higher MN induction was observed with fractionated doses. DCFHDA test clearly demonstrated ROS induction with H2O2 and menadione but not with KBrO3. Unexpectedly, DCFHDA test demonstrated that KBrO3 did not cause an increase ROS levels in both acute and chronic dosing, suggesting an alternative ROS induction mechanism. It was also observed that, treatment with BSO and NAC, caused increasing and decreasing of MN fold change respectively, allowing further ROS specific mechanisms to be explored. Hence, dose fractionation expectedly caused less MN, cytotoxicity and ROS formation with H2O2 and menadione exposure, but not with KBrO3. This implies a unique mechanism of action for KBrO3 induced genotoxicity. Chronic dosing in vitro may be a valuable approach allowing better understanding of how chemicals damage DNA and pose human hazards. [ABSTRACT FROM AUTHOR]

The development of modern technology and the growing industrial age have led to a more widespread occurrence of occupational diseases related to a variety of toxic metals, especially because some of them are carcinogenic. Lithium has been used extensively in the treatment of certain neuropsychiatric disorders.In our current study, the genotoxicity of Lithium carbonate was evaluated in mouse bone marrow cells using the micronucleus (mni) test, chromosome aberrations in bonemarrow cells. Lithium carbonate was administered to whit mice by gavage in doses of 300, 600 and 900 mg/kg.b wt and used Retinoic acid as the positive control (0.001 mg/kg. bwt.) intrapretonial injection. The results of current study shows that three experimental doses of Lithium carbonate 300, 600, 900 mg/kg. bwt. induced a significant increase p ≤ 0.05 in the frequency of MN(11.4±1.080, 1608±1.080 and 37.00±1.080) compared with the negative control. Significant increase p ≤ 0.05 in means of total numerical structural chromosome aberrations (1.00 ± 0.48, 2.00 ± 0.48 and 2.00 ± 0.48) and in structural chromosome aberrations (10.2± 0.84, 13.2± 0.84 and 15.6± 0.84) compared with of negative control in bone marrow. These results propose that Lithium carbonate has genotoxic potential in vivo tests. Our study indicate that lithium carbonate is good candidate for further in vivo therapeutic trials. [ABSTRACT FROM AUTHOR]

Prostate cancer (PC) is commonly diagnosed cancer in men but only a few risk factors, such as family history, ethnicity, and age have been established. Chromosomal instability is another possible risk factor but this has not been adequately explained previously. In this study, we tested the hypotheses that peripheral blood lymphocytes (PBL) of PC patients have (1) an abnormally high level of chromosomal instability; (2) that they are hypersensitive to ionizing radiation‐induced DNA damage; and (3) that these phenotypes are affected by hOGG1 (C1245G) polymorphism. These experiments were performed using the cytokinesis‐block micronucleus Cytome (CBMN cyt) assay in PC cases and controls. We found that spontaneous or radiation‐induced (3G) micronucleus (MN) frequency is not significantly different between both groups. However, spontaneous frequency of nucleoplasmic bridges (NPBs) and radiation‐induced nuclear buds (NBuds) were significantly higher in patients vs. controls (P < 0.0001; P = 0.0005, respectively). In addition, apoptosis and nuclear division index (NDI) was significantly higher in patients compared to controls after radiation treatment (P = 0.006; P = 0.0002, respectively). Furthermore carriage of at least one G allele of hOGG1 (C1245G) polymorphism was associated with a significantly increased odds ratio (OR) to have a base‐line MN, NPB, or NBud frequency greater than medium level compared to homozygotes for C allele (OR:1.94, 1.77, 2.36, respectively, P = 0.02; 0.04, and 0.004, respectively). Our results support the hypotheses that those who develop PC have significantly higher level of genomic instability which is further increased in those who carry G allele of the hOGG1 (C1245G) polymorphism. Environ. Mol. Mutagen. 59:813–821, 2018. © 2018 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

This study aimed at analyzing the frequency of micronuclei (MN) in exfoliated cells as well as the levels of Pb-210 in urine samples to evaluate the association between the smoking habit and toxic stress of transitional epithelial cells. The frequency of MN was scored from Giemsa-stained slides while exchange resin and beta counting techniques were employed to measure the concentrations of this radioisotope. Urine samples of smokers had levels of Pb-210 up to 158.65 mBq L −1 . For nonsmokers, the median was below the detection limit (45 mBq L −1 ). The analyses of mononucleated cells showed a significant increase of the frequency of MN in smokers when compared to nonsmokers. Statistical tests showed a tight relation between the cigarette consumption and the increase of the frequency of MN, rather than with the levels of Pb-210 present in smoke particles. The results indicate the usefulness of the methodology for the evaluation of human health risks related to chronic contamination with Pb-210. [ABSTRACT FROM AUTHOR]

Evaluation of the Genotoxicity of Zinc Oxide-Eugenol Cement in Allium cepa L. Dental materials can induce local and systemic effects. The Allium cepa assay was used to evaluate the genotoxicity and/or cytotoxicity of zinc oxide and eugenol (ZOE) at different proportions. The ZOE solution was tested at the concentration of 1 drop of eugenol (in each drop of liquid, the approximate concentration of eugenol is 85%) and 1 portion of zinc oxide cement (treatment I), and twice the concentration of eugenol (treatment II). Treated roots appeared to be yellowish-brown, fewer in number, thicker and less turgid compared with the control, suggesting a cytotoxic activity of ZOE. A significant difference was found in the root size between the control and treatment II. This treatment reduced by 79% the size of the root compared with the control, and the mitotic index was 66%, indicating a 22.4% reduction relative to the control, which in turn evidenced the cytotoxicity of ZOE. The significant increase in anaphase bridges suggests a genotoxic effect.

The micronucleus (MN) assay on exfoliated buccal cells is a useful and minimally invasive method for monitoring genetic damage in humans. To determine the genotoxic effects of calcite dust that forms during processing, MN assay was carried out in exfoliated buccal cells of 50 (25 smokers and 25 non-smokers) calcite factory workers and 50 (25 smokers and 25 non-smokers) age- and sex-matched control subjects. Frequencies of nuclear abnormalities (NA) other than micronuclei, such as binucleates, karyorrhexis, karyolysis and 'broken eggs', were also evaluated. Micronuclei and the other aforementioned anomalies were analysed by two way analysis of covariance. The linear correlations between the types of micronucleus and nuclear abnormalities were determined by Spearman's Rho. There was a positive correlation between micronuclei and other types of nuclear abnormalities in accordance with the Spearman's Rho test. Results showed statistically significant difference between calcite fabric workers and control groups. MN and NA frequencies in calcite fabric workers were significantly higher than those in control groups (p < 0.05). The results of this study indicate that calcite fabric workers are under risk of significant cytogenetic damage.

Purpose:It is well known that a high-dose of ionizing radiation is sufficient to break DNA strands, which leads to elevated genotoxic risks; however, the risks associated with low doses of ionizing radiation remain unclear. In addition, there is little data about the effect of low-dose ionizing radiation on human-derived embryo, newborn and child cells. We investigated the frequency of micronucleus (MN) formation in these cells to understand the genotoxic effects of ionizing radiation. Materials and methods:We irradiated the cells with X-rays from 0.02–2 Gy at a rate of 0.0635 Gy/min. After irradiation, we investigated the effect of low-dose X-ray irradiation on cellular viability and frequency of MN formation. Results:Increases in MN formation were largely dose-dependent; however, there were no differences between controls and doses lower than 0.2 Gy, except in KMST-6 human transformed embryo cells. Conclusion:We could not detect an obvious effect of low-dose X-ray irradiation at doses lower than 0.1 Gy. The embryonic cells were more sensitive to X-ray irradiation than newborn and child cells. The threshold for X-ray-induced MN formation appears to be in the range of 0.05–0.1 Gy in cultured human embryo, newborn and child cells. [ABSTRACT FROM AUTHOR]

Highlights: [•] Genotoxic effects of nicotine between 1μM and 1mM for 1h were investigated. [•] Experiments were performed in vitro in primary cells of human parotid glands. [•] Acinar character of cell culture was proven by alpha-amylase expression. [•] Increase of DNA migration, micronuclei and chromosome aberrations were determined. [•] No cytotoxic effects or an increase of Caspase-3 were measured. [Copyright &y& Elsevier]

Highlights: [•] Chromosome aberrations and micronucleus were higher in smokeless tobacco users. [•] High levels of DNA damage was found in smokeless tobacco users. [•] Homozygous variants of XRCC1 and p53 genes were found among tobacco users. [•] XRCC1 and p53 variants are associated with cancer risk. [ABSTRACT FROM AUTHOR]

The neonicotinoid insecticide imidacloprid (IMI) affects the insect central nervous system and is successfully applied to control pests for a variety of agricultural crops. In the current study, acute toxicity and genotoxicity of the IMI-containing commercial formulation insecticide Glacoxan Imida (35 percent IMI) was evaluated on Hypsiboas pulchellus (Anura: Hylidae) tadpoles exposed under laboratory conditions. A lethal effect was evaluated as the end point for lethality, whereas micronucleus (MN) frequency and DNA single-strand breaks evaluated by the single cell gel electrophoresis (SCGE) assay were employed as end points for genotoxicity. Sublethal end points were assayed within the 12.5–37.5mg/L IMI concentration range. Experiments were performed on tadpoles at stage 36 (range, 35–37) according to the classification proposed by Gosner. Lethality studies revealed an LC50 96h value of 52.622mg/L IMI. Increased frequency of MNs was only observed when 25.0mg/L was assayed for 96h, whereas no other nuclear abnormalities were induced. Increase of the genetic damage index was observed at 48h of treatment within the 12.5–37.5mg/L concentration range, whereas an increased frequency of DNA damage was observed only in tadpoles treated with 37.5mg/L IMI for 96h. This study represents the first evidence of the acute lethal and genotoxic effects exerted by IMI on tadpoles of an amphibian species native to Argentina under laboratory conditions. [Copyright &y& Elsevier]

Highlights: [•] Piperine was negative in an in vivo MNT in bone marrow cells up to the MTD. [•] Piperine is not genotoxic in CHO cells. [•] The hypothermic and hematotoxic effects of piperine did not results in increased micronuclei frequencies in the in vivo MNT. [ABSTRACT FROM AUTHOR]

Highlights: [•] Deoxynivalenol could be considered as a non in vitro genotoxin. [•] DON failed to induce gene mutation in bacteria. [•] DON did not induced micronucleus formation in TK6 and HepaRG cells. [ABSTRACT FROM AUTHOR]

Highlights: [•] We investigated the in vitro genotoxic, cytotoxic and apoptogenic properties of FLC and FLC-based herbicides. [•] FLC and its formulations Twin Pack Gold® and Rainbow® were evaluated on HepG2 cells. [•] FLC and its formulations were able to induce single-strand DNA breaks. [•] Only Twin Pack Gold® increased the frequency of MN at 5μg/ml. [•] FLC and its two commercial formulations trigger apoptosis on HepG2 at least for 24h. [ABSTRACT FROM AUTHOR]

Highlights: [•] Toxicity study of organoalkoxysilanes used in food contact coatings is proposed. [•] The genotoxicity was assessed with the Ames test and in vitro micronucleus assay. [•] No mutagenic effect was detected for TEOS and MTES. [•] A significant positive response was observed with GPTES in the TA100 and TA1535. [ABSTRACT FROM AUTHOR]

Highlights: [•] The genotoxic effect of TCBQ on HepG2 cells was discussed. [•] SCGE, MN, γ-H2AX, 8-OHdG and ROS assays were conducted. [•] TCBQ-induced genotoxicity is associated with oxidative stress. [•] NAC administration significantly alleviates TCBQ-induced genotoxicity. [Copyright &y& Elsevier]

Highlights: [•] Toxicogenomics-based follow-up in case of positive genotoxicity results is tested. [•] A case study of triclosan, a cosmetic preservative, is presented. [•] Triclosan is positive in in vitro genotoxicity tests, but negative in vivo. [•] Toxicogenomics data identifies triclosan as a non-DNA reactive compound. [•] Toxicogenomics-based in vitro assays can be a possible weight-of-evidence follow-up. [Copyright &y& Elsevier]

Abstract: The accident with the oil tanker Prestige in November 2002 resulted in a major spill of about 63,000 tons of heavy fuel oil. More than 300,000 people participated in the clean-up activities, which lasted for up to 10 months. Previous studies reported increases in genotoxicity endpoints in individuals exposed to Prestige oil, both at the moment of exposure [DNA breakage, micronuclei (MN), sister chromatid exchange] and two years later (chromosomal aberrations). In this work we carried out for the first time the follow-up of genotoxic effects in subjects exposed to an oil spill seven years after the exposure. The main objective was to determine the possible persistence of genotoxic damage in individuals exposed to Prestige oil seven years after the accident. The exposed group was composed of 54 residents of Galician villages in Spain that were heavily affected by the spill. This group was involved in clean-up labor for at least two months in the period November 2002–September 2003. They were compared with 50 matched controls. Primary DNA damage was evaluated by the comet assay, mutagenicity by the T-cell receptor (TCR) mutation assay, and MN frequency was determined both by the cytokinesis-block test and by flow cytometry. The results obtained showed no significant differences between the exposed and the controls in the comet assay, the TCR mutation assay and the cytokinesis-block MN test. An unexpected and significant decrease was observed in the exposed group for the results of the MN test evaluated by flow cytometry, probably influenced by modifying factors – other than age, sex and smoking – not considered in this study. Our results show no evidence of the persistence of genotoxic damage in individuals exposed to Prestige oil seven years later. Nevertheless, the need to plan biomonitoring studies on people participating in clean-up activities in case a new oil spill occurs should be established. [Copyright &y& Elsevier]

Highlights: [•] We show the possibility of modulate proliferation induced by radiation-induced bystander effect with low concentration carbon monoxide. [•] Carbon monoxide inhibited proliferation via modulating the transforming growth factor β1 (TGF-β1)/nitric oxide (NO) signaling pathway. [•] Exogenous carbon monoxide has potential application in clinical radiotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Ochratoxin A (OTA), a mycotoxin, causes extensive cell damage, affecting liver and kidney cells. OTA toxicity is fairly well characterized where oxidative stress is believed to play a role, however, the sequence of molecular events after OTA-exposure, have not been characterized in literature. Further, antidotes for alleviating the toxicity are sparsely reported. The aim of this study was to understand the sequence of some molecular mechanisms for OTA-induced toxicity and the cytoprotective effect of quercetin on OTA-induced toxicity. Methods: Time course studies to evaluate the time of intracellular calcium release and ROS induction were carried out. The time of activation and induction of two key redox- sensitive transcription factors, NF-κB and Nrf-2 were determined by nuclear localization and expression respectively. The time of expression of inflammatory marker COX-2 was determined. Oxidative DNA damage by comet assay and micronucleus formation was studied. The ameliorative effect of quercetin on OTA-induced toxicity was also determined on all the above-mentioned parameters. Results: OTA-induced calcium release, ROS generation and activated NF-κB nuclear translocation and expression. Pre-treatment with quercetin ameliorated ROS and calcium release as well as NF-κB induction and expression. Quercetin induced Nrf-2 nuclear translocation and expression. Quercetin's anti-inflammatory property was exhibited as it down regulated COX-2. Anti-genotoxic effect of quercetin was evident in prevention of DNA damage and micronucleus formation. Conclusion: Quercetin modulated OTA-induced oxidative stress and redox-signaling in HepG2 cells. General significance: The results of the study demonstrate for the first time that quercetin prevents OTA-induced toxicity in HepG2 cells. [Copyright &y& Elsevier]

In an effort to characterize the pollution of surface waters by potentially genotoxic agents, this study aimed at assessing the frequency of micronucleated (MN) erythrocytes of the fish species, Oreochromis niloticus, from the Cubatão do Sul River. This river is the source of drinking water for the region of Florianópolis, capital of Santa Catarina State, Brazil. Negative control fish showed low frequency of MN, ranging between 0.49‰ and 0.90‰. Positive control (potassium dichromate 2.5mg/L) organisms showed high MN frequency (16.82–17.25‰). The MN frequency increased along the river (Site 1 – 1.24‰ winter 2011; Site 4 – 9.76‰ summer 2011). Based on the observation of elevated MN erythrocytes frequency in O. niloticus exposed to water samples from along the river course, we conclude that the complex environmental mixtures of water from the Cubatão do Sul River have genotoxic potential. This genotoxicity most likely originated from agricultural runoff and domestic effluents released without treatment, based on the evidence from literature data and a survey in the region. This study provides a scientific basis for future studies regarding the genotoxicity of complex environmental mixtures in natural environments. [Copyright &y& Elsevier]

Highlights: [•] Gill cells are in direct contact with potentially stressing compounds in water. [•] Epithelial gill cells are more sensitive than erythrocytes for comet assay in Prochilodus lineatus. [•] Gill cell DNA damage increased after alkylation (MMS) and oxidative damage (H2O2). [•] Cypermethrin caused significant increase in epithelial gill cell DNA damage. [•] This is useful information for biomonitoring of P. lineatus naturally exposed to pesticides. [Copyright &y& Elsevier]

During the past few decades, urban and suburban developments have grown at unprecedented rates and extents with unknown consequences for ecosystem function. The problem of soil pollution as a result of the accelerating development of Guangzhou in China is becoming great concerns. In the present study, gas chromatograph coupled mass spectrometry (GC-MS), inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma atomic emission spectrometry (ICP-AES) were employed to determine the 16 US Environmental Protection Agency (EPA) priority polycyclic aromatic hydrocarbons (PAHs) and the heavy metals (As, Cr, Cu, Pb, Cd, Hg, and Se) of soils collected from suburban areas of Guangzhou. The genotoxicity of these soils was screened with micronucleus (MN) assay inVicia fabaroot cells. The concentrations of the pollutants in the soils were (dried weight): ΣPAHs (230.6–1263 ng·g−1), As (2282.6–36064 μg·kg−1), Cr (7109–64699 μg·kg−1), Cu (7047–56388 μg·kg−1), Pb (9675.9–93739 μg·kg−1), Cd (68.5–847.3 μg·kg−1), Hg (85.4–549.2 μg·kg−1), and Se (219.2–968 μg·kg−1), which fell in the moderately polluted range. However, six out of nine soil-exposed groups had a significant increases of MN frequencies observed in theV. fabaroot cells compared with the negative group (P< 0.05,P< 0.01), indicating that they had potential genotoxic risks. Bringing together the chemical analyses with the biological effects observed in this study, the genotoxic response could at a certain degree be explained by both the soil PAHs and heavy metals. Our results suggested that apart from chemical analysis, bioassays like the MN assay ofV. fabaroot cells should also be included in a battery of tests to assess the eco-environmental risks of urban and/or urbanization in the developing areas on the soils. [ABSTRACT FROM AUTHOR]

Highlights: [•] The efficiency of two methods for landfill leachate purification was investigated. [•] Untreated leachate proved to be both cyto- and genotoxic to human or plant cells. [•] Treated leachate did not cause increase in cyto- and genotoxic damage. [•] Both methods have high removal efficiency and provide toxicological safety. [Copyright &y& Elsevier]

Highlights: [•] Cold aqueous extract (CAE) of A. satureioides showed low toxicity in vitro on Vero cells and human PBMCs. [•] CAE does not induce apoptosis on human PBMCs. [•] CAE at high concentrations showed genotoxic capacity in vitro on Vero cells by comet assay. [•] CAE did not induce in vivo genotoxicity, but it shows at high concentrations toxic effects by micronucleus assay. [•] CAE of A. satureioides shows the presence of quercetin, 3-O-methylquercetin and luteolin. [ABSTRACT FROM AUTHOR]

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Highlights: [•] Diabetes was induced in mice by intravenous injection of alloxan. [•] EGCG and propolis significantly increased survival of diabetic mice. [•] EGCG and propolis significantly decrease lipid peroxidation of diabetic mice. [•] EGCG and propolis reduced DNA damage in peripheral lymphocytes of diabetic mice. [•] EGCG and propolis could contribute to the prevention and treatment of diabetes. [ABSTRACT FROM AUTHOR]

Highlights: [•] Cu2+-exposure of mussels results in genotoxicity, without affecting MTs production. [•] Cd2+-exposure of mussels causes low genotoxicity, but induces MTs production. [•] Both metals induce oxidative stress in mussels, with Cd being the strongest inducer. [•] Translation is suppressed by both metals, mainly at the initiation and elongation steps. [•] MTs abrogate translational defects caused by Cd2+, by trapping the toxic metal. [Copyright &y& Elsevier]

Highlights: [•] We examined genotoxicity of quincetone cyadox and olaquindox in five different tests. [•] Olaquindox was found genotoxic in all tests. [•] Quinocetone had toxic effect in three in vitro tests at higher concentrations. [•] Cyadox had mutagenic effects only in Ames test. [•] This study provided useful information about genotoxicity of quinocetone, cyadox and olaquindox. [ABSTRACT FROM AUTHOR]

Abstract: Mercury is an element naturally occurring in the biosphere, but is also released into the environment by human activities, such as mining, smelting, and industrial discharge. Mercury is a biologically harmful element and any exposure of living organisms mainly due to contamination, can cause severe or even lethal side effects. In every form detected, elemental, inorganic, or organic, mercury exhibits toxicity associated with induced oxidative stress. Although the genotoxicity of mercury has been well demonstrated in mussels, little is known about its toxic effects on the translational machinery at the molecular level. To investigate possible effects, we exposed the common mussel Mytilus galloprovincialis in seawater supplemented by 30μg/L Hg2+ for 15 days. We observed that Hg2+ was significantly accumulated in the digestive glands of mussels, reaching a level around 80μg/g tissue (dry weight) at the 15th day of exposure. Exposure of mussels to Hg2+ resulted in failure of redox homeostasis, as reflected on lipid peroxidation levels and superoxide dismutase activity in glands, and micronucleus frequency in gills. Extracts from digestive glands after 15-day exposure to Hg2+ exhibited decreased tRNA aminoacylation ability and, moreover, a 70% reduction in the ability of 40S ribosomal subunits to form the 48S initiation ribosomal complex. A similar reduction was detected in the ability of ribosomes to translocate peptidyl-tRNA from the A-site to the P-site, an observation coinciding with the notion that regulation of protein synthesis by Hg2+ mainly occurs at the initiation and elongation stages of translation. A-site binding, peptidyl transferase activity, and termination of peptide chain synthesis underwent less pronounced but measurable reductions, a finding which explains why poly(Phe)-synthesis in ribosomes isolated from exposed mussels is reduced by 70%. In conclusion, Hg2+ apart from being a genotoxic ion acts as a modulator of protein synthesis in mussels, an observation probably related with its ability to induce oxidative stress. [Copyright &y& Elsevier]

Abstract: The genotoxic potential of the vaccine adjuvant Squalene was assessed by the chromosomal aberrations (CAs), sister chromatid exchanges (SCEs) and micronucleus (MNs) tests in human lymphocytes and comet assay in both human and rat lymphocytes. Five different concentrations of squalene (1250–20,000μg/ml for human lymphocytes and 0.07–1.12mg/kg for rat lymphocytes) were studied. Squalene did not affect the CAs and MN frequency, in all treatments in vitro. A significant increase in SCEs was observed in almost all concentrations at 24h treatment. Squalene did not affect significantly the comet tail length (CTL) (except 2500μg/ml) and comet tail intensity (CTI) at all treatments in vitro. In rats, squalene significantly increased and decreased CTL and CTI in some doses. Although there are increasing and reduction in the effect, squalene cannot be regarded as genotoxic in human lymphocytes. However, further in vivo studies are required to be sure on the effect. [Copyright &y& Elsevier]

Highlights: [•] Insulin produces DNA damage in mammalian colon cells and human lymphocytes in vitro. [•] Insulin stimulates mitochondrial and NADPH oxidase derived ROS production. [•] Antioxidants, mitochondrial and NADPH inhibitors reduce the genotoxicity of insulin. [Copyright &y& Elsevier]

Abstract: Acitretin is currently used alone or combined with PUVA (psoralen + UVA) or with narrow-band ultraviolet B (NBUVB), to treat moderate and severe psoriasis. However, little is known about the potential genotoxic/carcinogenic risk and the cytostatic/cytotoxic effects of these treatments. Our aim was to study the cytotoxic and genotoxic effects of acitretin – alone or in combination with PUVA or NBUVB – by performing studies with blood from patients with psoriasis vulgaris who were treated with acitretin, acitretin+PUVA or acitretin+NBUVB for 12 weeks, and in vitro studies with blood from healthy volunteers, which was incubated with acitretin at different concentrations. The cytotoxic and genotoxic effects were evaluated by the cytokinesis-blocked micronucleus test and the comet assay. Our results show that psoriatic patients treated with acitretin alone or with acitretin+NBUVB, did not show genotoxic effects. In addition, these therapies reduced the rate of proliferation and induced apoptosis and necrosis of lymphocytes; the same occurred with lymphocyte cultures incubated with acitretin (1.2–20μM). The acitretin+PUVA reduced also the proliferation rate, and increased the necrotic lymphocytes. Our studies suggest that therapy with acitretin alone or combined with NBUVB, as used in psoriatic patients, does not show genotoxic effects, reduces the rate of proliferation and induces apoptosis and necrosis of lymphocytes. The combination of acitretin with PUVA also reduces the proliferation rate and increases the number of necrotic lymphocytes. However, as it induced slight genotoxic effects, further studies are needed to clarify its genotoxic potential. [Copyright &y& Elsevier]

Abstract: Fexofenadine (FXF) is a new non-sedating antihistamine used in the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria. Studies on FXF genotoxicity and cytotoxicity in cultured human peripheral blood lymphocytes have not been reported so far. Therefore, the present study is the first report investigating the genotoxic and cytotoxic effects of FXF in cultured human peripheral blood lymphocytes in vitro. Cultures were treated with FXF at three concentrations (50, 100 and 150μg/ml) for 24 and 48h. Endpoints analyzed included: mitotic index (MI), nuclear division index (NDI), chromosomal aberrations (CA) and micronucleus (MN) assay. Mitomycin C (MMC) was used as a positive control. The results of CA and MN assays showed that FXF was not genotoxic at all the concentrations tested, meanwhile MI and NDI results showed dose-dependent decrease and significant differences were found for at least one concentration. In conclusion, the results of this study suggest that FXF has a cytotoxic effect but not genotoxic effect on human peripheral blood lymphocyte cultures. Further cytogenetic studies, especially about the cell cycle kinetics of FXF are required to elucidate the decreases in dividing cells, and biomonitoring studies should also be conducted with patients receiving therapy with this drug. [Copyright &y& Elsevier]

The aim of this article is to elucidate the mechanism by which eicosapentaenoic acid (EPA) acts against cyclophosphamide (CP)-induced effects. The prevalence of micronuclei, the extent of lipid peroxidation, and the status of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) in both liver and serum of mice were used as intermediate biomarkers of chemoprotection. Lipid peroxidation and associated compromised antioxidant defenses (CAT and GPX) in CP treated mice were observed in the liver, serum, and were accompanied by increased prevalence of micronuclei in bone marrow. The number of MN was significantly different ( p < 0.01) between the groups treated with CP (group III, IV, V, VI) and the solvent control (group II) (3.2 ± 0.7‰). There was a dose-dependent reduction in formation CP induced micronuclei by treatment with 100, 200, or 300 mg EPA/kg BW mice. Activities of SOD, CAT, and extent of lipid peroxidation were statistically different in liver cells of mice exposed to EPA only with CP compared with the CP group (group III). The present findings imply that EPA may be a potential antigenotoxic, antioxidant and chemopreventive agent and could be used as an adjuvant in chemotherapeutic applications. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2011. [ABSTRACT FROM AUTHOR]

The focal aim of this study was to assess the frequency of chromosomal aberrations (CA) including chromatid type aberrations (CTA) and chromosomal type aberrations (CSA), micronucleus (MN) and XRCC1 399 Arg/Gln polymorphism in the peripheral blood lymphocytes of 27 petrol pump workers and same number of controls to explore the possible cytogenetic risk on occupational exposure to petrol vapors. The exposed subjects and controls were classified into two groups based on their age (group I < 40 years; group II > 40 years) apart from the classification of the exposed subjects based on their exposure duration (> 8 and < 8 years). CTA and MN frequency were significantly higher in petrol pump workers ( p < 0.05) with longer work duration. CTA was found to increase with age in the exposed subjects as well as controls, with exposed subjects showing a statistically higher degree. This effect was not observed in MN. A significantly higher frequency of MN was observed in the smoking petrol pump workers than in control smokers ( p < 0.05). No association was found between smoking and CA in both subjects. The study on XRCC1 399 Arg/gln polymorphism in petrol pump workers demonstrated very less difference in allele frequency compared to controls. In conclusion, these datas indicate that petrol pump workers under risk group should be monitored for any long-term adverse effects of the exposure . [ABSTRACT FROM AUTHOR]

Abstract: The present study evaluates the genotoxic potential of potassium sorbate (PS) in cultured and isolated human lymphocytes. To assess the damage caused by PS in humans, we designed in vitro experiments by measuring chromosomal aberrations (CAs), sister-chromatid exchanges (SCEs), micronucleus (MN) and comet assays. Lymphocytes were treated with negative control (sterile distilled water), positive control (MMC for cultured lymphocytes, and H2O2 for isolated lymphocytes) and four concentrations (125, 250, 500, and 1000μg/ml) of PS. According to the results, PS treatment significantly increases the CAs (with or without gaps at 500 and 1000μg/ml concentrations) and SCEs (at 250, 500, 1000μg/ml for 24h and 125, 250, 500, 1000μg/ml for 48h) compared with vehicle control. Following treatment of the isolated lymphocytes for 1h, significant PS-induced DNA strand breaks were observed, at all concentrations. However, PS failed to significantly affect the MN assay. On the contrary, PS does not cause cell cycle delay as noted by the non-significant decrease in the cytokinesis-block proliferation index (CBPI) and replicative index (RI). Only a slight decrease was observed in the mitotic index (MI) at the highest concentration for both treatment times. From the results, PS is clearly seen to be genotoxic to the human peripheral blood lymphocytes in vitro. [Copyright &y& Elsevier]

Abstract: With increasing use of municipal solid waste landfills for waste disposal, the leachate generated has become a serious environmental concern. Therefore, it is important to set up simple and accurate methods for monitoring leachate toxicity. In the present study, the physiological and genetic toxicity of the leachate, generated from Xingou Municipal Landfill in China, were investigated with Triticum aestivum (wheat) bioassay. The results indicate that the lower leachate concentrations stimulated the germination, growth and cell division, and did not induce obvious increase in micronucleus (MN) frequency in root tips; while the higher concentrations inhibited the processes, and significantly augmented the MN frequency in a concentration- and time-dependent manner. In addition, pycnotic cells (PNC) and sister chromatid exchange (SCE) occurred in root tips at all leachate concentrations tested, and the frequencies had positive relation with the treatment concentration and time. The results imply that components of leachate from the landfill may be genotoxic in plant cells, and exposure to leachate in the aquatic environment may pose a potential genotoxic risk to organisms. The results also suggest that the wheat bioassay is efficient, simple and reproducible in monitoring genotoxicity of the leachate. [Copyright &y& Elsevier]

Abstract: The effect of trifluoperazine (TFP), a phenothiazine derivative antipsychotic drug, on ionizing radiation (IR) induced cell killing through inhibition of DNA repair was investigated in human cell lines. In clonogenic survival assay, TFP augmented IR induced cell killing. Also, TFP enhanced micronucleus formation in irradiated human lymphocytes. The effect of TFP and other known DNA repair inhibitors like wortmannin and caffeine, on irradiated cells, was compared by MTT assay. On the other hand, TFP failed to increase the toxicity induced by H2O2. Repair of DNA double strand breaks induced by IR was markedly inhibited by TFP, as determined by field inversion gel electrophoresis (FIGE). Further, TFP increased radiation induced apoptosis, which was accompanied by enhanced G2/M arrest. Thus, our results strongly suggest that TFP inhibits repair of DNA damage induced by IR, which significantly implicates the possibility of using TFP as an adjuvant to radiotherapy. [Copyright &y& Elsevier]

In the present study, degradation of endosulfan by a mixed culture isolated from a pesticide-contaminated soil was studied in batch experiments. After two weeks of incubation, the mixed culture was able to degrade 73% and 81% of α and β endosulfan respectively. Endodiol was identified by GC/MS as degradation intermediate. The toxicity studies of endosulfan before and after degradation were carried out using micronucleus assay on human polymorphonuclear cells. The findings suggested that the metabolism of endosulfan isomers by the mixed culture was accompanied by significant reduction in the toxicity. Studies were also carried out to quantify the degradation potential of the individual species in the mixed bacterial culture. Two cultures identified by 16S rRNA as Stenotrophomonas maltophilia and Rhodococcus erythropolis were found to be responsible for majority of the degradation by the mixed culture. S. maltophilia showed better degradation efficiency compared to that by R. erythropolis. This is the first report of endosulfan degradation using the above-mentioned organisms. [Copyright &y& Elsevier]

Objective To study the modulatory effect of distillate of Ocimum sanctum (traditionally known as Tulsi) leaf extract (DTLE) on genotoxicants. Methods In the present investigation, we studied the antigenotoxic and anticlastogenic effect of distillate of Tulsi leaf extract on (i) human polymorphonuclear leukocytes by evaluating the DNA strand break without metabolic activation against mitomycin C (MMC) and hexavalent chromium (Cr+6) and (ii) human peripheral lymphocytes (in vitro) with or without metabolic activation against mitomycin C (MMC), hexavalent chromium (Cr+6) and B[a]P by evaluating chromosomal aberration (CA) and micronucleus assay (MN). Three different doses of DTLE, 50 μL/mL, 100 μ L/mL, and 200 μL/mL were selected on the basis of cytotoxicity assay and used for studying DNA strand break, chromosomal aberration and micronucleus emergence. The following positive controls were used for inducing genotoxicity and clastogenicity: MMC (0.29 μmol/L) for DNA strand break, chromosomal aberration and 0.51 μmol/L for micronucleus assay; Potassium dichromate (Cr+6) 600 pmol/L for DNA strand break and > μmol/L for chromosomal aberration and micronucleus assay; Benzo[a]pyrene (30 μmol/L) for chromosomal aberration and 40 pmol/IL for micronucleus assay. The active ingredients present in the distillate of Tulsi leaf extract were identified by HPLC and LC-MS. Results Mitomycin C (MMC) and hexavalent chromium (Cr+6) induced statistically significant DNA strand break of respectively 69% and 71% (P<0.00 1) as revealed by fluorometric analysis of DNA unwinding. Furthermore, the damage could be protected with DTLE (50 μL/mL, 100 μL/mL, and 200 μL/mL) on simultaneous treatment. Chromosomal aberration and micronucleus formation induced by MMC, Cr+6 and B[a]P were significantly protected (P<0.001) by DTLE with and without metabolic activation. Conclusion Distillate of Tulsi leaf extract possesses antioxidants contributed mainly by eugenol, luteolin and apigenin as identified by LC-MS. These active ingredients may have the protective effect against genotoxicants. [ABSTRACT FROM AUTHOR]

Exposure to asbestos minerals has been associated with a wide variety of adverse health effects including lung cancer, pleural mesothelioma, and cancer of other organs. Many of the regions of Turkey have asbestos deposits. People in Doğanlı village - one of these regions - have been environmentally exposed to chrysotile asbestos since they were born. In this study the effects of asbestos on micronucleus (MN) frequencies of inhabitants exposed to chrysotile asbestos have been examined. Thirty subjects who had been environmentally exposed to chrysotile asbestos and living in Doğanlı village, and 25 controls were studied to assess the MN frequency. The control group was selected from healthy individuals with no exposure to asbestos and living in similar geographic conditions to Doğanlı village. Peripheral blood samples were collected from each subject and cultured for MN assay. Cytochalasin-B was added to lymphocyte cultures for evaluation of MN in binucleated (BN) cells. The differences between those exposed to chrysotile asbestos and controls were not statistically significant in terms of BN cells with MN (p > 0.05). There was not a significant relationship between MN frequencies and age, sex, smoking, both in chrysotile asbestos-exposed subjects and in controls (p > 0.05). Although the detection of calcified pleural plaques found in the inhabitants has indicated environmental exposure to chrysotile asbestos, our results show that chrysotile asbestos was not an inducer of MN in subjects exposed to chrysotile asbestos. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to investigate the genotoxic effects of potassium bromate, which is used as a bleaching agent in flour, on human peripheral blood lymphocytes in vitro by sister chromatid exchange (SCE), chromosomal aberrations (CA) and micronucleus (MN) tests, and also to determine whether it has any genotoxic potential for humans. Cells were treated with 400, 450, 500, 550μg/ml concentrations of potassium bromate for 24 and 48h. The SCE frequencies showed an increase after both treatment periods, however, the differences between the treated cells and the control groups were found to be statistically significant only for the 48-h treatment. In addition, potassium bromate statistically significantly induced CA after the 24-h and 48-h treatment periods. Strikingly, potassium bromate induced CA as much as the positive control, mitomycin-C (MMC). Furthermore, potassium bromate decreased both the cell proliferation index (PI) and the mitotic index (MI). Although micronucleus formation was induced by potassium bromate during the 24-h treatment period in a dose-dependent manner, only the doses 500 and 550μg/ml yielded statistically significant results. In contrast, MN formation was significantly induced at all doses during the 48-h treatment period. These in vitro results provide important evidence about genotoxicity of potassium bromate on a human cell culture system. [Copyright &y& Elsevier]

Aim of the study was to investigate the usefulness of two human derived hepatoma cell lines (HepG2 and Hep3B) for the detection of dietary and lifestyle related DNA-reactive carcinogens. Comparisons of the sensitivity of HepG2 cells of different origin towards benzo[a]pyrene (B(a)P) showed that strong differences exist in the induction of micronuclei (MN). The most sensitive was used for all further experiments, in which we investigated the effects of aflatoxin B1 (AFB1), B(a)P, As2O3, CdCl2, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), N-nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), ethanol, acetaldehyde and caffeic acid in micronucleus (MN) tests. Dose dependent effects were detected in HepG2 with AFB1 (0.2 μM), CdCl2 (2.2 μM), As2O3 (8.1 μM), B(a)P (22.7 μM), PhIP (35.7 μM), NDMA (22.7 mM), acetaldehyde (11.2 mM) and ethanol (442.2 mM). Numbers in parentheses indicate the CD values (concentration that induced a two-fold increase over the background). NNK and caffeic acid gave negative results under all conditions. In Hep3B cells, the effects were generally weaker. With PhIP, As2O3 and NDMA negative results were obtained; with caffeic acid and NPYR marginal but significant induction of MN was observed. Enzyme measurements showed that both cell lines possess CYP1A1, glutathione-S-transferase (three-fold higher in HepG2) as well as N-acetyltransferase (NAT) 1 and sulfotransferases (SULT1A1 and SULT1A3; two- and seven-fold higher in HepG2); other cytochrome P450 enzymes (CYP1A2, 2B1, 2E1) and NAT2 were not detectable. The differences in the activities of the various enzymes may explain the contrasting results obtained in the MN experiments. Overall, our results indicate that the HepG2 line is more sensitive towards dietary genotoxins than Hep3B, and support the assumption that the HepG2/MN assay enables the detection of genotoxic carcinogens which give negative results in other currently used in vitro assays. [Copyright &y& Elsevier]