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Computed tomography (CT) is known for its non-invasiveness, fast procedure, and also for providing detailed diagnostic information to physicians. It also utilises low-dose-rate ionising radiation (X-rays) as a source for imaging. Multidetector computed tomography (MDCT) is an advanced system that uses iodinated contrast media for more accurate diagnostic results. Studies suggest using these contrasts will lead to greater radiation adsorption with significant DNA damage. No studies have been taken comparing the physical dose with the biological effect. The present study sheds light on the same by assessing the biological effect of CT with and without contrast intervention. The present study is timebound; thus, 21 participants attending for CT thorax and abdomen with no history of any cancer were included. The same participants underwent both pre-contrast and post-contrast studies. The blood sample was taken before the procedure and used as a control. Physical parameters like DLP and CTDI obtained from the instrument were compared with the MN frequency obtained (CBMN Assay). The study showed a significant increase (p-value < 0.05) in the Physical and MN frequency in the Post-Contrast group compared to the pre-contrast group. Although a positive correlation was observed between pre and post-contrast groups, the results were not found to be statistically significant (p-value < 0.05). The study confirms increased physical dose and MN frequency upon contrast intervention. This study recommends the judicial use of MDCT in disease diagnostics. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effect of aqueous and acetone extracts from Artemisia vulgaris L. (AV) and Artemisia alba Turra (AA), and two major polyphenols compounds (3,5-dihydroxybenzoic acid and quercetin-3-O-glucopyranoside) presented in both extracts of the plants against mitomycin C (MMC)-induced genomic instability. Genomic instability was measured using cytokinesis block micronucleus (MN) assay in human peripheral blood lymphocytes (PBLs) in vitro by analyzing two biomarkers – MN and nuclear division index (NDI). Extracts were tested in a concentration-dependent manner (10–250 µg/mL), while 3,5-dihydroxybenzoic acid and quercetin-3-O-glucopyranoside were tested in three different concentrations, in combination with 0.5 µg/mL of MMC. Aqueous and acetone extracts obtained from both plants significantly reduced MMC-induced MN frequency in PBLs, compared to positive control cells (p < 0.05). Extracts from AV did not affect NDI, whereas the concentrations of 10–100 μg/mL of aqueous and acetone AA extracts significantly elevated MMC-decreased NDI values in comparison to positive control cells (p < 0.05). Combined treatment of 3,5-dihydroxybenzoic acid and MMC showed a significant reduction of MMC-induced MN frequency, while quercetin-3-O-glucopyranoside increased MN frequency compared to positive control cells (p < 0.05). Both compounds decreased NDI values but only at the highest tested concentration of quercetin-3-O-glucopyranoside it was of greater significance. In conclusion, all extracts from AV and AA and 3,5-dihydroxybenzoic acid showed protective effect, whereby aqueous AA demonstrated the highest protective effect on MMC- induced genomic instability, while quercetin-3-O-glucopyranoside showed co-mutagen effect. [ABSTRACT FROM AUTHOR]

Major strides have been made in the development of FLASH radiotherapy (FLASH RT) in the last ten years, but there are still many obstacles to overcome for transfer to the clinic to become a reality. Although preclinical and first-in-human clinical evidence suggests that ultra-high dose rates (UHDRs) induce a sparing effect in normal tissue without modifying the therapeutic effect on the tumor, successful clinical translation of FLASH-RT depends on a better understanding of the biological mechanisms underpinning the sparing effect. Suitable in vitro studies are required to fully understand the radiobiological mechanisms associated with UHDRs. From a technical point of view, it is also crucial to develop optimal technologies in terms of beam irradiation parameters for producing FLASH conditions. This review provides an overview of the research progress of FLASH RT and discusses the potential challenges to be faced before its clinical application. We critically summarize the preclinical evidence and in vitro studies on DNA damage following UHDR irradiation. We also highlight the ongoing developments of technologies for delivering FLASH-compliant beams, with a focus on laser-driven plasma accelerators suitable for performing basic radiobiological research on the UHDR effects. [ABSTRACT FROM AUTHOR]

This study comprises the phytochemical characterization, the evaluation of the total phenolic content (TPC) and antioxidant activity (AA), and the investigation of the cyto-genotoxic and antigenotoxic potential of hydromethanolic extract derived from Salvia verticillata L. leaves. HPLC–DAD–ESI-MS and HPLC–DAD were used for the characterization of the extract and determination of the major ingredients. Afterwards, the TPC and AA were determined. The cytotoxic and genotoxic effect of the extract on cultured human lymphocytes at concentrations of 10, 25, and 50 μg mL−1 was investigated via the Cytokinesis Block MicroNucleus (CBMN) assay. Moreover, its antigenotoxic potential against the mutagenic agent mitomycin C (MMC) was assessed using the same assay. The hydromethanolic extract comprises numerous metabolites, with rosmarinic acid being the major compound. It had a high value of TPC and exerted significant AA as shown by the results of the Ferric Reducing Antioxidant Power (FRAP) and Radical Scavenging Activity by DPPH• assays. A dose-dependent cytotoxic potential was recorded, with the highest dose (50 μg mL−1) exhibiting statistically significant cytotoxicity. None of the tested concentrations induced significant micronuclei (MN) frequencies, indicating a lack of genotoxicity. All tested concentrations reduced the MMC-mediated genotoxic effects, with the two lowest showing statistically significant antigenotoxic potential. [ABSTRACT FROM AUTHOR]

This study comprises the phytochemical characterization, the evaluation of the total phenolic content (TPC) and antioxidant activity (AA), and the investigation of the cyto-genotoxic and antigenotoxic potential of hydromethanolic extract derived from Salvia verticillata L. leaves. HPLC–DAD–ESI-MS and HPLC–DAD were used for the characterization of the extract and determination of the major ingredients. Afterwards, the TPC and AA were determined. The cytotoxic and genotoxic effect of the extract on cultured human lymphocytes at concentrations of 10, 25, and 50 μg mL−1 was investigated via the Cytokinesis Block MicroNucleus (CBMN) assay. Moreover, its antigenotoxic potential against the mutagenic agent mitomycin C (MMC) was assessed using the same assay. The hydromethanolic extract comprises numerous metabolites, with rosmarinic acid being the major compound. It had a high value of TPC and exerted significant AA as shown by the results of the Ferric Reducing Antioxidant Power (FRAP) and Radical Scavenging Activity by DPPH• assays. A dose-dependent cytotoxic potential was recorded, with the highest dose (50 μg mL−1) exhibiting statistically significant cytotoxicity. None of the tested concentrations induced significant micronuclei (MN) frequencies, indicating a lack of genotoxicity. All tested concentrations reduced the MMC-mediated genotoxic effects, with the two lowest showing statistically significant antigenotoxic potential.

This study investigated the beneficial properties of prickly pear peel (PPP) extracts from Opuntia ficus-indica (L.) Mill. Extracts were obtained via the Soxhlet extraction method using methanol (P1), ethanol (P2) and ethanol-water (P3) as extraction solvents. Their total phenolic and flavonoid content (TPC and TFC, respectively) and their antioxidant activity (AA) were determined. The PPP extracts were characterized in detail using mass spectrometry techniques. Their cyto-genotoxic effect and antigenotoxic potential against mitomycin C were evaluated via the cytokinesis block micronucleus (CBMN) assay on human lymphocytes. Enhanced TPC, TFC and AA values were recorded for all the extracts. Moreover, P1 and P2 were cytotoxic only at the highest concentrations, whereas P3 was found to be cytotoxic in all cases. No significant micronucleus induction was observed in the tested extracts. The PPP extracts contain bioactive compounds such as flavonoids, carboxylic acids, alkaloids, fatty acids and minerals (mainly K, Si, Mg, Ca, P and Zn). The results showed that all three extracts exerted high antigenotoxic activity. Our findings confirm the beneficial and genoprotective properties of PPP extracts and further studies on the bioactive compounds of Opuntia ficus-indica (L.) Mill. are recommended, as it constitutes a promising plant in pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Nuclear imaging is a highly sensitive and noninvasive imaging technique that has become essential for medical diagnosis. The use of radiolabeled nanomaterials capable of acting as imaging probes has shown rapid development in recent years as a powerful, highly sensitive, and noninvasive tool. In addition, quantitative single-photon emission computed tomography (SPECT) images performed by incorporating radioisotopes into nanoparticles (NPs) might improve the evaluation and the validation of potential clinical treatments. In this work, we present a direct method for [99mTc]Tc-radiolabeling of FITC-tagged silk fibroin nanoparticles (SFN). NPs were characterized by means of dynamic light scattering and scanning electron microscopy. In vitro studies were carried out, including the evaluation of stability in biological media and the evaluation of hemocompatibility and genotoxicity using the cytokinesis block micronucleus (CBMN) assay. The radiolabeling method was reproducible and robust with high radiolabeling efficiency (∼95%) and high stability in biological media. Hydrodynamic properties of the radiolabeled NPs remain stable after dual labeling. The interaction of SFN with blood elicits a mild host response, as expected. Furthermore, CBMN assay did not show genotoxicity induced by [99mTc]Tc-FITC-SFN under the described conditions. In conclusion, a feasible and robust dual-labeling method has been developed whose applicability has been demonstrated in vitro, showing its value for further investigations of silk fibroin NPs biodistribution in vivo. [ABSTRACT FROM AUTHOR]

In this study, the genotoxic activity of acetone and aqueous extracts of two species of genus Artemisia (Artemisia vulgaris L. and Artemisia alba Turra), and possible role of their polyphenolic composition in the observed activities were investigated. Polyphenolic contents were evaluated by high-performance liquid chromatography (HPLC-PDA), while the genotoxic activity was tested using cytokinesis block micronucleus (CBMN) assay on human peripheral blood lymphocytes (PBLs) in vitro. HPLC-PDA showed that both A. alba extracts were richer in polyphenolic contents than A. vulgaris extracts. The acetone A. alba extract was the richest of polyphenolic content where we detected six phenolic acids and two flavonoids. CBMN assay showed that aqueous extract of A. vulgaris significantly increased micronucleus (MN) frequency in the PBLs treated with all tested concentrations (10, 50, 100, and 250 µg/mL), while A. alba did not significantly affect the mean MN frequency. Further, both acetone extracts were genotoxic in all tested concentrations, except the lowest tested (10 µg/mL) of A. alba. All tested extracts affected the nuclear division index (NDI) except the aqueous A. alba extract (p < 0.05). Based on our results, we can conclude that both acetone and aqueous A. vulgaris extracts and A. alba acetone extract were genotoxic in PBLs in vitro. A. alba aqueous extract was not genotoxic and cytotoxic in tested concentrations. We suggest that the aqueous extract of A. alba can be used in treatment, which has been confirmed by traditional medicine, but with a high dose of caution and not in high concentrations. [ABSTRACT FROM AUTHOR]

The present study investigated the cyto-genotoxic and antigenotoxic effects of four different extracts of Equisetum arvense L. (common name: field horsetail) on human lymphocytes. Specifically, Soxhlet's prepared extracts from E. arvense L., using different solvents (S1: methanol (MeOH)-, S2: ethanol (EtOH)-, S3: water-, and S4: ethanol/water (EtOH-W)-) were analyzed for (a) their total phenolic and flavonoid content (TPC and TFC, respectively), (b) their antioxidant activity (AA), via the DPPH, FRAP and ABTS assays, and (c) their cyto-genotoxic and/or protective efficiency against the mutagenic agent mitomycin C, via the Cytokinesis Block MicroNucleus assay. All extracts showed increased TPC, TFC, and AA values in almost all cases. S1, S3 and S4 demonstrated no cytotoxic potential, whereas S2 was cytotoxic only at the highest concentrations. Genotoxicity was not observed in the tested extracts. The highest antigenotoxic activity was observed for EtOH-W (S4) extract, which was found to be rich in flavonoids, flavonoid-O-glycosides, phytosterols, phenolic and fatty acids as well as in minerals and mainly in K, Ca, Mg, Si and P, as assessed by using various mass spectrometry techniques. Those findings confirm that E. arvense L. extracts could be valuable candidates for medicinal applications and pharmaceutical products, thus alleviating the effects of more conventional drugs. [ABSTRACT FROM AUTHOR]

Biological dosimetry, using chromosome damage biomarkers, can be considered as a key measure for radiation overexposure assessment. Therefore, for accurate dose estimation through biodosimetry, it's imperative for each biological dosimetry laboratory to establish its own specific dose-response calibration curve. In this research, the cytokinesis-blocked micronucleus (CBMN) assay was utilized to determine the frequencies of micronuclei (MN) per binucleated cell in human peripheral blood lymphocytes exposed to x-ray radiation using a LINAC (6 MV) at doses up to 4 Gy. The aim was to establish an in vitro dose-response calibration curve in our laboratory for the Iranian demographic by analyzing blood samples of ten participants (5 males and 5 females) through CABAS and Dose Estimate software. Our findings indicate an over-dispersion of the Poisson distribution in the pooled data across both sexes, coupled with a linear-quadratic increase in MN yield with dose which was particularly pronounced in the female group. The constructed dose-response curves for micronuclei yield are represented by equations Y= (0.0102 ± 0.0016) +(0.0296 ± 0.0054) D+(0.0232 ± 0.0017) D2 and Y= (0.0084 ± 0.0010) +(0.0212 ± 0.0034) D+(0.0160 ± 0.0011) D2 for the female groups, respectively. The alpha and beta coefficients, derived from the Dose Estimate software for each male and female group, were closely comparable with those obtained from the CABAS program and previous studies. The analysis of statistical parameters such as the Weighted Chi Squared (χ2) and p-value suggests that using distinct curves for each sex, rather than a unified biodosimetry formula for pooled data, ensures more accurate radiation dose estimates. Consequently, the findings of this study provide us with the assurance to utilize the derived calibration curve of MN for upcoming biological dosimetry needs in Iran. However, to enhance the reliability of results, it's essential to use biodosimetry with diverse assays and consider all clinical and physical parameters, given the limitations of cytogenetic assays. • Sex-specific biodosimetry curves improve radiation dose accuracy, as shown by χ2 and p-value analysis. • MN over-dispersion and higher frequencies in females, especially at high doses, highlight sex influences on MN formation. • The alpha and beta coefficients, derived from the Dose Estimate software for each sex group matched CABAS and prior studies. [ABSTRACT FROM AUTHOR]

This study investigated the beneficial properties of prickly pear peel (PPP) extracts from Opuntia ficus-indica (L.) Mill. Extracts were obtained via the Soxhlet extraction method using methanol (P1), ethanol (P2) and ethanol-water (P3) as extraction solvents. Their total phenolic and flavonoid content (TPC and TFC, respectively) and their antioxidant activity (AA) were determined. The PPP extracts were characterized in detail using mass spectrometry techniques. Their cyto-genotoxic effect and antigenotoxic potential against mitomycin C were evaluated via the cytokinesis block micronucleus (CBMN) assay on human lymphocytes. Enhanced TPC, TFC and AA values were recorded for all the extracts. Moreover, P1 and P2 were cytotoxic only at the highest concentrations, whereas P3 was found to be cytotoxic in all cases. No significant micronucleus induction was observed in the tested extracts. The PPP extracts contain bioactive compounds such as flavonoids, carboxylic acids, alkaloids, fatty acids and minerals (mainly K, Si, Mg, Ca, P and Zn). The results showed that all three extracts exerted high antigenotoxic activity. Our findings confirm the beneficial and genoprotective properties of PPP extracts and further studies on the bioactive compounds of Opuntia ficus-indica (L.) Mill. are recommended, as it constitutes a promising plant in pharmaceutical applications.

Three novel composite nanomaterials, namely Clay/CNTs, GO/ADMA and Clay/ADMA were synthesized and tested for their genotoxic, mutagenic and cytotoxic potential. The cytokinesis block micronucleus (CBMN) assay, applied in human lymphocytes in vitro, demonstrated a lack of genotoxic activity of all three composite nanomaterials at all tested doses i.e. 10, 25 and 50 μg mL−1. As far as their cytotoxicity is concerned, statistically significant cytotoxic activity was shown at the two highest doses (25 and 50 μg mL−1) of Clay/CNTs and GO/ADMA whereas Clay/ADMA possessed slightly statistically significant cytotoxic potential only at the highest dose. Similarly, the in vivo SMART assay showed no increase in the frequency of the spontaneous mutation spots in Drosophila melanogaster indicating lack of genotoxic activity of all three composite nanomaterials tested at concentrations ranging from 100-4000 μg mL−1. The present data assess the toxic profile of novel composite nanomaterials, demonstrating the plausible differences with their respective base counterparts and the ability to alleviate genotoxic effects leading potentially to further uses in medicinal applications.

The present study investigated the cyto-genotoxic and antigenotoxic effects of four different extracts of Equisetum arvense L. (common name: field horsetail) on human lymphocytes. Specifically, Soxhlet’s prepared extracts from E. arvense L., using different solvents (S1: methanol (MeOH)-, S2: ethanol (EtOH)-, S3: water-, and S4: ethanol/water (EtOH-W)-) were analyzed for (a) their total phenolic and flavonoid content (TPC and TFC, respectively), (b) their antioxidant activity (AA), via the DPPH, FRAP and ABTS assays, and (c) their cyto-genotoxic and/or protective efficiency against the mutagenic agent mitomycin C, via the Cytokinesis Block MicroNucleus assay. All extracts showed increased TPC, TFC, and AA values in almost all cases. S1, S3 and S4 demonstrated no cytotoxic potential, whereas S2 was cytotoxic only at the highest concentrations. Genotoxicity was not observed in the tested extracts. The highest antigenotoxic activity was observed for EtOH-W (S4) extract, which was found to be rich in flavonoids, flavonoid-O-glycosides, phytosterols, phenolic and fatty acids as well as in minerals and mainly in K, Ca, Mg, Si and P, as assessed by using various mass spectrometry techniques. Those findings confirm that E. arvense L. extracts could be valuable candidates for medicinal applications and pharmaceutical products, thus alleviating the effects of more conventional drugs.

Radioprotector is the prime antidote to radiation injury. The desire to search an ideal radioprotector led us to explore natural sources. Bamboo species are known for theirimmense medicinal potential such as antioxidant, anti-inflammatory, anti-cancer, immunomodulatory activities and are enriched with polyphenolic phytoconstituents. In CBMN assay, the pre-treatment of human peripheral blood lymphocytes with varying concentration of bamboo leaf extract before exposure to different doses of γ-radiation resulted in significant (P < 0.0001) decline of radiation induced micronuclei. Among all the selected species, Bambusa arundinacea showed highest protection ~70% at 9 μg/mL concentration. Through RP-HPLC analysis, compared to other species, B. arundinacea showed presence of all selected polyphenols to the highest extent. The results favour the direct correlation of radioprotective activity and the amount of polyphenol, indicating the role of bamboo polyphenols as radioprotector against gamma radiation induced genetic damage. [ABSTRACT FROM AUTHOR]

Abstract Considering the necessity to monitor rainwater quality and the limited existing data regarding wet precipitations' toxic potential, the toxic potential of rainwater (RW) samples collected in three cities of Western Greece (Corfu, Agrinion and Patras) during May, October, November, and December of 2014 were investigated. The relationship of the adverse effects obtained, against cytokinesis block micronucleus (CBMN) and Vibrio fischeri bioluminescence (Microtox) assays with the physicochemical characteristics, the heavy metal concentration levels of rainwater samples and the meteorological parameters governing the climatic conditions in each region, were studied in detail. All samples showed pH values in the range of 5.37–7.17, high concentrations of ΝΗ 4 + and the presence of SO 4 2− and NO 3 −. The metals Al, Mn, Fe, Co, Ni, Cu, Zn, As, Sb, Cd, were detected in most of the samples, with maximum concentrations ranging from 0.16 μg L−1 (for Co) to 86.6 μg L−1 (for Fe). The CBMN assay showed statistically significant rainwater cytotoxic activity at 5% (v/v) concentration in all cities during all months studied and at 10% (v/v) in Agrinion and Corfu in May. No genotoxic effect was induced at 5% (v/v) concentration of rainwater, except for Corfu city during November, whereas 10% (v/v) of rainwater led to statistically significant increase in micronuclei frequencies in all three cities. The highest (100%) and the lowest (14%) inhibitory effect exhibited by the rainwater in the Vibrio test were noticed at Corfu city during May and December, respectively. Considering the inter-relations obtained among the abiotic and biotic variables measured in all cases, conductivity, SO 4 2−, NH 4 +, and total metal burden could be related with both CBMN and Microtox assays data, regardless of the site- and month-specific differences. The multidisciplinary approach presented here showed that the physicochemical profile of rainwater precipitation could be significantly related with the induction of adverse effects on biota. Graphical abstract Unlabelled Image Highlights • The toxic potential of rainwater samples from three cities of Western Greece was evaluated. • Chemical and biological assays were combined to assess the toxic potential of the rainwater samples. • High concentrations of ΝΗ 4 + and the presence of SO 4 2− and NO 3 were observed. • Al, Mn, Fe, Co, Ni, Cu, Zn, As, Sb, Cd were detected in most of the samples. • All rainwater samples in all three cities induced cytotoxicity. [ABSTRACT FROM AUTHOR]

Highlights • AT patients showed a delay in the repair process, compared with controls. • Study groups demonstrate inability to repair cells with large amounts of DNA damage. • CBMN and repair evaluation were effective to distinguish heterozygotes from controls. Abstract Ataxi A-T elangiectasia (AT) is a multisystem, complex and rare disease inherited in an autosomal recessive manner. Homozygous individuals have a variety of pathological manifestations, however, heterozygotes only present a higher risk of developing cancer. We evaluated the background levels of DNA damage (basal damage) and cell response to bleomycin or ionizing radiation using Comet assay and the cytokinesis-block micronucleus (CBMN) test in individuals with AT, their parents and controls. To evaluate DNA repair, the challenge experiment with ionizing radiation was performed using Comet assay, and different recovery times were evaluated. Results showed that basal MN frequencies differ between patients, parents and controls. Meanwhile, using the Comet assay, the results from the basal analysis do not differ between the groups, but monitoring the kinetics of DNA repair, we verified that the group of patients showed a delay in repair, compared to controls. Another finding was the nuclear bud (NBUD) frequency: spontaneous and induced cell cultures (with bleomycin and radiation) showed clear differences between patients, parents and controls. The CBMN assay and repair measurement with the Comet assay can help in the diagnosis of AT patients and ATM gene carriers, as complementary methods. The use of genomic instability evaluation techniques for the identification of the heterozygotes in families, where at least one member is affected, may be of great clinical importance. [ABSTRACT FROM AUTHOR]

Introduction: Radiosensitivity is an inherent trait, associated with a raised reaction to ionizing radiation on the human body. In radiotherapy and radiation protection fields, individualization of the patient’s treatment is one of the main topics. With the goal of determining biomarkers capable of anticipating normal tissue side reactions, we studied the association between the Rh factor and radiosensitivity. Methods: This experimental study was carried out from January to June 2014 among 50 normal responders with A blood group (25Rh+ and 25Rh-) between the ages of 22 and 23 in Babol, Iran. Human peripheral blood samples were taken from subjects and, using CBMN assay, the biological effects of gamma irradiation, including the frequency of micronuclei (MN) and nuclear division index (NDI), were measured. A data analysis was performed using SPSS version 18 to determine the independent and paired samples t-tests. Results: A significant increment occurred in the frequency of MN in group Rh+ (196 ± 18.23) compared with Rh- (169 ± 17.11) following irradiation (p

Translocation of mtDNA in the nuclear genome is an ongoing process that contributes to the development of pathological conditions in humans. However, the causal factors of this biological phenomenon in human cells are poorly studied. Here we analyzed mtDNA insertions in the nuclear genome of human lymphocytes after in vitro treatment with doxorubicin (DOX) using a fluorescence in situ hybridization (FISH) technique. The number of mtDNA insertions positively correlated with the number of DOX-induced micronuclei, suggesting that DOX-induced chromosome breaks contribute to insertion events. Analysis of the odds ratios (OR) revealed that DOX at concentrations of 0.025 and 0.035 µg/mL significantly increases the rate of mtDNA insertions (OR: 3.53 (95% CI: 1.42–8.76, p < 0.05) and 3.02 (95% CI: 1.19–7.62, p < 0.05), respectively). Analysis of the distribution of mtDNA insertions in the genome revealed that DOX-induced mtDNA insertions are more frequent in larger chromosomes, which are more prone to the damaging action of DOX. Overall, our data suggest that DOX-induced chromosome damage can be a causal factor for insertions of mtDNA in the nuclear genome of human lymphocytes. It can be assumed that the impact of a large number of external and internal mutagenic factors contributes significantly to the origin and amount of mtDNA in nuclear genomes.

This study evaluates the genotoxic potential of two Ru(III) complexes with thiosemicarbazone based ligands. The complexes were tested for in vitro protective effect on chromosome aberrations in peripheral human lymphocytes using the cytokinesis block micronucleus (CBMN) assay at concentrations 1.5; 3.7 and 7.4 μg/mL. The cell culture treated with the tested complexes, at 3.7 μg/mL concentration, decreased a frequency of micronucleus for 37% and 32%, when compared with the control cell cultures. At concentration of 7.4 (1.5) μg/mL of this complexes exhibited slightly lower effect of micronucleus for 30% (35%) and 27% (29%), when compared with the control cell cultures. [ABSTRACT FROM AUTHOR]

The present study investigated [omim][BF 4 ]-mediated adverse effects on biological models widely used in toxicological studies. Specifically, mussels of the genus Mytilus , human lymphocytes and fruit flies of the species Drosophila melanogaster , were exposed to [omim][BF 4 ] at concentrations ranging from micro- to milligrams per liter, with or without the presence of acetone as a carrier solvent and thereafter [omim][BF 4 ]-mediated adverse effects were analyzed appropriately (stress indices, such as lipid peroxidation byproducts, acetylcholinesterase/AChE activity and micronucleus/MN formation frequency, in mussel gills, Cytokinesis Block Micronucleus/CBMN assay and SMART test in human lymphocytes and fruit flies respectively). LC–MS–TOF analysis was also performed for elucidating [omim][BF 4 ] mode of action in the presence of the carrier solvent. The results showed the toxic potential of [omim][BF 4 ], as well as acetone’s ability to attenuate [omim][BF 4 ]-mediated toxicity in almost all cases, probably due to the significant effect of acetone on the hydrophilic-lipophilic character and the viscosity of [omim][BF 4 ], as well as its interaction and permeability on the cell membranes. The slight involvement of acetone in the attenuation of [omim][BF 4 ]-mediated genotoxic effects on D. melanogaster could be due to species feeding experimental conditions, thus favoring the induction of antioxidant defense system against the [omim][BF 4 ]-mediated effects in all cases. [ABSTRACT FROM AUTHOR]

Flavonoids are reported to exhibit a wide variety of biological effects including antioxidant activities. The present study aims to explore the protective effect of the flavonol quercetin against hydrogen peroxide-mediated damage. The effects of quercetin on H2O2-mediated DNA damage were evaluated using spectrophotometric analyses, DNA damage monitoring by gel electrophoresis, cell viability, CBMN assay, comet assay and chromosomal aberration study inhuman peripheral blood lymphocytes. Quercetin was found to be protective at 30 μM in the cell viability study, while it showed its maximum efficacy in the CBMN assay and comet assay at a concentration level of 40 μM against H2O2-induced damage. Spectrophotometric analyses speculated that the intercalation is the possible binding mode of quercetin with DNA and prevented oxidative stress-induced DNA damage. This study successfully establishes quercetin as a protective agent against oxidative DNA damage induced by H2O2. [ABSTRACT FROM AUTHOR]

Dextran-coated superparamagnetic iron oxide nanoparticles (dextran-SPION) have been commercially used for medical applications, such as magnetic imaging or targeted drug delivery, etc. Despite of this usefulness, there are continuous controversies on safety/toxicity of various SPIONs. In the case of dextran-SPION, the reported adverse effects include the cytotoxicity, oxidative stress and DNA damage in many cell types. In this study, the genetic toxicity of dextran-SPION in human hepatoma (HepG2) cells was evaluated with comet assay and cytokinesis-block micronucleus (CBMN) assay. Dextran-SPION did not inhibit cell proliferation as a function of dose and time. The comet assay indicated that 5 μg/mL of dextran-SPION induced a significant DNA strand breaks. A dose-dependent increase of the micronucleus (MN) frequency was observed in CBMN assay. The formation of intracellular reactive oxygen species (ROS) in HepG2 cells was induced by dextran-SPION. The results demonstrated that dextran-SPION exerted genetic toxicity in HepG2 cells. Also, it suggests that a mechanism by which dextran-SPION triggers the DNA and chromosomal damage in HepG2 cells may be via the generation of intracellular ROS. [ABSTRACT FROM AUTHOR]

The links between diet and genomic instability have been under investigation for several decades, and evidence suggests a significant causal or preventive role for various dietary factors. This study investigates the influence of macronutrients (calories, protein, and glucides) and micronutrients, such as vitamins and minerals, as assessed by a food frequency questionnaire, on genotoxicity biomarkers measured by cytokinesis-blocked micronucleus assay and comet assay. The results found significant positive and negative correlations. Micronucleus frequency tends to increase with higher intake of caffeine, calcium, magnesium, zinc, and protein (P < .05, Spearman correlation). Calorie and omega-6 intakes are negatively correlated with DNA damage measured by the comet assay. These results are somewhat controversial because some of the correlations found are contrary to dominant views in the literature; however, we suggest that unraveling the association between diet and genetic instability requires a much better understanding of the modulating role of macronutrients and micronutrients. [ABSTRACT FROM AUTHOR]

This study investigated the phytochemical profile of Drimia numidica leaf methanolic extract, as well as its cyto-genotoxic and cyto/genoprotective potential against mitomycin C (MMC) mediated effects on healthy human lymphocytes. Photosynthetic pigments, trace elements, and secondary metabolites were estimated and/or identified in methanolic extract of mature leaves, and the latter was further used for assessing its in vitro biological effects on MMC-free and/or MMC-treated human lymphocytes (at low, non-toxic concentrations of 0.001 and 0.01% v/v). The results showed that D. numidica leaf methanolic extract, being rich in carotenoids, phenolics, flavonoids, organic acids and bufadienolides, could be protective against MMC mediated cyto/genotoxic potential in healthy human lymphocytes. Biomolecules possessing antioxidant and antitumor potential, such as beta-carotene and lutein among others, chlorogenic acid, caffeic acid and their derivatives, minerals such as Si, as well as apigenin- and luteolin-derived glycosides, either individual or in a mixture, could be beneficial rather than harmful, at least at the extract concentrations tested. Although further in vitro and in vivo studies are still needed for elucidating the beneficial (individual and/or additive/synergistic) role of those compounds, the results of the present study are quite promising, thus encouraging new challenges for the appropriate utilization of D. numidica leaf extract. • The biological properties of Drimia numidica leaf methanolic extract were examined. • Human lymphocytes, treated with or without mitomycin C, were used. • D. numidica leaf methanolic extract was phytochemically analyzed. • Extract was no cyto-genotoxic on human lymphocytes at the tested concentrations. • Extract was cyto/genoprotective against mitomycin C at the tested concentrations. [ABSTRACT FROM AUTHOR]

Epidemiological studies for hazardous situations resulting from the risk of environmental and/or occupational exposure to miscellaneous chemicals present several difficulties. Biomonitoring of human populations can provide an early detection system for the initiation of cell dysregulation in the development of cancer, which would help develop an efficient prevention program. Recently, the cytokinesis-block micronucleus (CBMN) assay in lymphocyte cells has become an important tool for assessing DNA damage in exposed populations. This is the method of choice for population-based studies of occupational and/or environmental exposure to different agents. In this review, human populations exposed to coal, dyes, paints, organic solvents in a complex mixture, and others miscellaneous chemicals were analyzed. Data from 28 studies was evaluated in relation to the effect of complex mixture exposition on micronucleus (MN) frequency. Other biomarkers and the background factors were evaluated as well, such as gender, age, or smoking habit. Most of these studies (75%) showed a significant increase of micronucleated cells to exposed groups in relation to the control groups, besides chromosomal aberrations (CA), sister chromatid exchanging (SCE) and comet cells (comet assay). The studies from this review about miscellaneous chemicals exposures using CBMN assay have indicated some time and dose-dependent effects. Overall, the findings suggest that the responses resulting from exposure to complex mixtures are varied and complicated. However, they are also an important mechanism of DNA damage concerning disruption of metal ion homeostasis that may lead to oxidative stress, a state where increased formation of reactive oxygen species (ROS) overwhelms body antioxidant protection and subsequently could induce cancer. [ABSTRACT FROM AUTHOR]

Styrene is a building-block of several compounds used in a wide array of materials and products. The most important human exposure to this substance occurs in industrial settings, especially among reinforced-plastics industry workers. The effect of occupational exposure to styrene on cytogenetics biomarkers has been previously reviewed with positive association observed for chromosomal aberrations, and inconclusive data for the micronucleus assay. Some limitations were noted in those studies, including inadequate exposure assessment and poor epidemiological design. Furthermore, in earlier studies micronuclei frequency was measured with protocols not as reliable as cytokinesis-block micronucleus (CBMN) assay. Aim of the present systematic review and meta-analysis is to investigate genomic instability and DNA damage as measured by the CBMN assay in lymphocytes of subjects exposed to styrene. A total of 11 studies published between 2004 and 2012 were included in the meta-analysis encompassing 479 styrene-exposed workers and 510 controls. The quality of each study was estimated by a quality scoring system which ranked studies according to the consideration of major confounders, exposure characterization, and technical parameters. An overall increase of micronuclei frequencies was found in styrene-exposure workers when compared to referents (meta-MR 1.34; 95% CI 1.18–1.52), with significant increases achieved in six individual studies. The consistency of results in individual studies, the independence of this result from major confounding factors and from the quality of the study strengthens the reliability of risk estimates and supports the use of the CBMN assay in monitoring genetic risk in styrene workers. [ABSTRACT FROM AUTHOR]

Introduction The aim of our work is to quantify the radiation damage in lymphocytes after labelling with [18F]FDG. Comparison with gold standard [99mTc]HMPAO labelling is established. An approach to cellular dosimetry is proposed. Methods Mixed leukocytes were separated from fresh venous blood and labelled with [18F]FDG and [99mTc]HMPAO following published guidelines. Cytokinesis-block micronucleus (CBMN) assay was performed for both sets of experiments. Tests for quality control of labelling described in guidelines were followed. Cellular dosimetry was calculated according to MIRD. Results MN scored after labelling with 37 MBq of [18F]FDG were 956 ± 172 and 347 ± 26 for [99mTc]HMPAO ( p < 0.05). Absorbed dose in cell nucleus was of 0.23 Gy for [18F]FDG and 0.08 Gy for [99mTc]HMPAO labelling. The CBMN assay after labelling with ~ 290 MBq of [18F]FDG showed radiation induced inhibition of proliferation capacity of the lymphocytes, confirmed by proliferation study. Conclusions [18F]FDG labelling of mixed leukocytes causes severe radiation damage to the cell, higher than with [99mTc]HMPAO in accordance with the absorbed dose. Labelling of mixed leukocytes for clinical purpose induces high cytotoxicity reflected in the loss of proliferation capacity in lymphocytes this statement allows us to consider a low oncogenic risk however the association between MN formation in the PBL and subsequent risk of cancer is not well established. Advances in knowledge This is the first work about radiation damage with [18F]FDG labelled cells. We focused on [18F]FDG labelling of leukocytes due to the growing number of research and review articles about this technique. Implications for patient care The possibility of an increased risk of lymphoid malignancies associated with the administration of radiolabelled lymphocytes is a very controversial subject. Studies on radiation damage on new labelling procedures as the one exposed in this work must be considered. [ABSTRACT FROM AUTHOR]

The chances of accidental exposure are augmented as the application of ionizing radiation increases in various fields. Such accidental exposures may occur at nuclear power plants, laboratories, and hospitals. Cytogenetic assays have been used for estimating radiation dose in the situation of the accidents. The micronucleus assay has several advantages over the other cytogenetic methods as it is simple and fast. The present study aimed at investigation of the micronuclei frequencies in cytokinesis-block cells in human blood lymphocytes after γ-irradiation and at establishment of a standard dose response relationship. The samples of peripheral blood were obtained from 6 different donors aged between 24 and 30 years old. The bloods were irradiated in vitro with 0-5 Gy. A linear quadratic dose-response equation was obtained by scoring the micronuclei in binucleated cells; y = 27.87x² + 46.13x + 2.08 (r² = 0.99). Irradiation caused a significant decrease in the nuclear division index. Necrotic and apoptotic cells increased in number after irradiation in a dose-dependent manner. In conclusion, the conventional cytokinesis-block micronucleus assay has proven to be the great technique in biological dosimetry. Dose-response calibration curve derived from CMBN assay could be used to estimate the exposure dose during a radiological emergency. [ABSTRACT FROM AUTHOR]

Although medical ultrasound offers compelling opportunities to improve therapy in principle, progress in the field has been limited because of an insufficient understanding of the potential genotoxic and cytotoxic effects of ultrasound on biological systems. This paper is mainly focused on an in vitro study of effects with respect to genotoxicity and viability induced by 1- and 3-MHz medical ultrasound in murine fibroblasts (NIH-3T3) at low-intensity exposure (spatial peak temporal average intensity Ita < 0.1 W/cm 2 ). The NIH-3T3 cells constitute a well-characterized in vitro cell model in which a genotoxic effect can be predicted by means of a reliable and precise murine cytokinesis-block micronucleus assay. A statistically significant increase in the incidence of micronuclei was observed in sonicated 3T3 cells. In particular, the effects were more evident at 1 MHz. Moreover, for each frequency investigated, the occurrence of micronuclei was comparatively more frequent with increasing time of exposure. The possible toxicological implications of the medical ultrasound employed herein deal with the existence of a window of exposure parameters (set well below the intensity of ultrasound cavitation) in which some genotoxic effects may occur without significant cytotoxicity. In this respect, they provide new insight toward the correct risk to benefit balancing of ultrasound-based treatments and for designing innovative therapeutic strategies. [ABSTRACT FROM AUTHOR]

The cytokinesis-block micronucleus cytome (CBMN) assay, introduced by Fenech, was used to demonstrate different types of DNA damage in MOLT-3 human lymphoblastoid cells exposed to 10 μM zidovudine (AZT). In addition, we explored the cytoprotective potential of two antioxidants, WR-1065 and Tempol, to decrease AZT-induced genotoxicity. Binucleated cells, arrested by Cytochalasin B (Cyt B), were evaluated for micronuclei (MN), caused by DNA damage or chromosomal loss, and chromatin nucleoplasmic bridges (NPBs), caused by telomere attrition. Additionally, nuclear buds (NBUDs), caused by amplified DNA, and apoptotic and necrotic (A/N) cells were scored. We hypothesized that AZT exposure would increase the frequency of genotoxic end points, and that the antioxidants Tempol and WR-1065 would protect against AZT-induced genotoxicity. MOLT-3 cells were exposed to 0 or 10 µM AZT for a total of 76 hr. After the first 24 hr, 0 or 5 µM WR-1065 and/or 0 or 200 µM Tempol were added for the remainder of the experiment. For the last 28 hr (of 76 hr), Cyt B was added to arrest replication after one cell division, leaving a predominance of binucleated cells. The nuclear division index (NDI) was similar for all treatment groups, indicating that the exposures did not alter cell viability. MOLT-3 cells exposed to AZT alone had significant ( P < 0.05) increases in MN and NBs, compared to unexposed cells. Both Tempol and WR-1065 protected against AZT-induced MN formation ( P < 0.003 for both), and WR-1065, but not Tempol, reduced the levels of A/N ( P = 0.041). In cells exposed to AZT/Tempol there were significantly reduced levels of NBUDs, compared to cells exposed to AZT alone ( P = 0.015). Cells exposed to AZT/WR-1065 showed reduced levels of NPBs, compared to cells exposed to AZT alone (P = 0.037). Thus WR-1065 and Tempol protected MOLT-3 cells against specific types of AZT-induced DNA damage. Environ. Mol. Mutagen. 55:566-572, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Combinations of genotoxic agents have frequently been assessed without clear assumptions regarding their expected (additive) mixture effects, often leading to claims of synergisms that might in fact be compatible with additivity. We have shown earlier that the combined effects of chemicals, which induce micronuclei (MN) in the cytokinesis-block micronucleus assay in Chinese hamster ovary-K1 cells by a similar mechanism, were additive according to the concept of concentration addition (CA). Here, we extended these studies and investigated for the first time whether valid additivity expectations can be formulated for MN-inducing chemicals that operate through a variety of mechanisms, including aneugens and clastogens (DNA cross-linkers, topoisomerase II inhibitors, minor groove binders). We expected that their effects should follow the additivity principles of independent action (IA). With two mixtures, one composed of various aneugens (colchicine, flubendazole, vinblastine sulphate, griseofulvin, paclitaxel), and another composed of aneugens and clastogens (flubendazole, doxorubicin, etoposide, melphalan and mitomycin C), we observed mixture effects that fell between the additivity predictions derived from CA and IA. We achieved better agreement between observation and prediction by grouping the chemicals into common assessment groups and using hybrid CA/IA prediction models. The combined effects of four dissimilarly acting compounds (flubendazole, paclitaxel, doxorubicin and melphalan) also fell within CA and IA. Two binary mixtures (flubendazole/paclitaxel and flubendazole/doxorubicin) showed effects in reasonable agreement with IA additivity. Our studies provide a systematic basis for the investigation of mixtures that affect endpoints of relevance to genotoxicity and show that their effects are largely additive. [ABSTRACT FROM AUTHOR]

Highlights: [•] MN dose–response curve for Portuguese population was performed for the first time. [•] 16 donors were studied to take in consideration the individual inter-variability. [•] The baseline value for the 16 donors is 12 micronuclei/1000 binucleated cells. [•] Y MN =(0.0122±0.0010)+(0.0241±0.0023)D +(0.0193±0.0007)D 2. [•] Larger inter-variability observed for the higher γ-radiation doses. [ABSTRACT FROM AUTHOR]

Positive health effects of tea ( Camellia sinensis) on a wide range of physiological problems and diseases are well known and are in part due to its copious antioxidant content. The effect of black tea extract (BTE), which is rich in polyphenolic antioxidants, against the consequences of radiation exposure has not been properly identified. The functional properties of BTE were analyzed and its radioprotective effect on V79 cells was explored in the present study. BTE scavenged free radicals and inhibited Fenton reaction-mediated 2-deoxyribose degradation and lipid peroxidation in a dose-dependent fashion, establishing its antioxidant properties. The radioprotective effects of BTE on strand break induction in pBR322 plasmid DNA were 100 % at 80 μg/ml and higher. In V79 cells, BTE was effective in decreasing the frequency of radiation-induced micronucleated cells and the yields of reactive oxygen species (ROS) and also in restoring the integrity of cellular mitochondrial membrane potential significantly. BTE exerted maximum protection against radiation-induced damage in V79 at a dose of 5 μg/ml. Due to the functional properties of BTE-flavonoids, which have been identified by HPLC, it is envisaged that the key player in radioprotection is elimination of ROS. [ABSTRACT FROM AUTHOR]

Abstract: Butachlor is a systemic herbicide widely applied on rice, tea, wheat, beans and other crops; however, it concurrently exerts toxic effects on beneficial organisms like earthworms, aquatic invertebrates and other non-target animals including humans. Owing to the associated risk to humans, this chloroacetanilide class of herbicide was investigated with the aim to assess its potential for the (i) interaction with DNA, (ii) mitochondria membrane damage and DNA strand breaks and (iii) cell cycle arrest and necrosis in butachlor treated human peripheral blood mononuclear (PBMN) cells. Fluorescence quenching data revealed the binding constant (Ka=1.2×104 M−1) and binding capacity (n =1.02) of butachlor with ctDNA. The oxidative potential of butachlor was ascertained based on its capacity of inducing reactive oxygen species (ROS) and substantial amounts of promutagenic 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) adducts in DNA. Also, the discernible butachlor dose-dependent reduction in fluorescence intensity of a cationic dye rhodamine (Rh-123) and increased fluorescence intensity of 2′,7′-dichlorodihydro fluorescein diacetate (DCFH-DA) in treated cells signifies decreased mitochondrial membrane potential (ΔΨm) due to intracellular ROS generation. The comet data revealed significantly greater Olive tail moment (OTM) values in butachlor treated PBMN cells vs untreated and DMSO controls. Treatment of cultured PBMN cells for 24h resulted in significantly increased number of binucleated micronucleated (BNMN) cells with a dose dependent reduction in the nuclear division index (NDI). The flow cytometry analysis of annexin V−/7-AAD+ stained cells demonstrated substantial reduction in live population due to complete loss of cell membrane integrity. Overall the data suggested the formation of butachlor–DNA complex, as an initiating event in butachlor-induced DNA damage. The results elucidated the oxidative role of butachlor in intracellular ROS production, and consequent mitochondrial dysfunction, oxidative DNA damage, and chromosomal breakage, which eventually triggers necrosis in human PBMN cells. [Copyright &y& Elsevier]

Abstract: Chronic anemia and tissue hypoxia increase intestinal iron absorption and mitochondrial impairment in thalassemic patients. Regular blood transfusions improve hemoglobin levels but determine an iron overload that induces reactive oxygen species (ROS) overproduction. The aim of this study was to assess cellular oxidative damage by detection of ROS, lipid peroxidation, 8-oxo-dG, and mitochondrial transmembrane potential (Δψm) in transfused and untransfused thalassemic patients. We have also evaluated genotoxicity by CBMN and comet assay. Our data show that ROS and lipid hydroperoxides are significantly higher in thalassemic patients than in controls, especially in untransfused thalassemia intermedia patients. Moreover, the latter have a significant decrease in Δψm that highlights the energetic failure in hypoxic state and the ROS overproduction in the respiratory chain. 8-OHdG levels are higher in thalassemics than in controls, but do not differ significantly between the two patient groups. Both genotoxicity biomarkers highlight the mutagenic potential of hydroxyl radicals released by iron in the Fenton reaction. Values for percentage of DNA in the comet tail and micronuclei frequency, significantly higher in transfused patients, could also be due to active hepatitis C virus infection and to the many drug treatments. Our biomonitoring study confirms the oxidative damage in patients with thalassemia major and shows an unexpected cellular oxidative damage in untransfused thalassemic patients. In addition to iron overload, the results highlight the important role played by hypoxia-driven mitochondrial ROS overproduction in determining oxidative damage in β-thalassemias. [Copyright &y& Elsevier]

Structural and functional effects of exposing murine fibroblasts (NIH 3T3) to therapeutic ultrasound at 1 MHz frequency are described. These bioeffects can be attributed to the formation of free radical species by sonolysis of water. When cavitation occurs, dissociation of water vapor into H atoms and OH radicals is observed; these H atoms and OH radicals combine to form H, HO, and HO. The radicals can chemically modify biomolecules, for example enzymes, DNA, and lipids. Generation of free radicals during exposure to ultrasound with or without encapsulated microbubbles (contrast agents) was studied by use of electron paramagnetic resonance with DMPO spin trapping. Recently the potential for possible use of these microbubbles in gene therapy has been investigated, because of the ability of the stabilized microbubbles to release their content when exposed to ultrasound. Structural changes were studied by Fourier-transform infrared spectroscopy, and induction of possible genotoxic damage by exposure of the cells to therapeutic ultrasound at 1 MHz frequency with our experimental device was verified by use of the cytokinesis-block micronucleus assay. [ABSTRACT FROM AUTHOR]

Abstract: Traffic is a major source of particulate matter (PM), and ultrafine particulates and traffic intensity probably contribute significantly to PM-related health effects. As a strong relationship between air pollution and motor vehicle-originated pollutants has been shown to exist, air pollution genotoxicity studies of urban cities are steadily increasing. In Korea, the death rate caused by lung cancer is the most rapidly increased cancer death rate in the past 10 years. In this study, genotoxicity of PM2.5 (<2.5μm in aerodynamic diameter particles) collected from the traffic area in Suwon City, Korea, was studied using cultured human lung bronchial epithelial cells (BEAS-2B) as a model system for the potential inhalation health effects. Organic extract of PM2.5 (CE) generated significant DNA breakage and micronucleus formation in a dose-dependent manner (1μg/cm3–50μg/cm3). In the acid–base–neutral fractionation of PM2.5, neutral samples including the aliphatic (F3), aromatic (F4) and slightly polar (F5) fractions generated significant DNA breakage and micronucleus formation. These genotoxic effects were significantly blocked by scavenging agents [superoxide dismutase (SOD), sodium selenite (SS), mannitol (M), catalase (CAT)]. In addition, in the modified Comet assay using endonucleases (FPG and ENDOIII), CE and its fractions (F3, F4, and F5) increased DNA breakage compared with control groups, indicating that CE and fractions of PM2.5 induced oxidative DNA damage. These results clearly suggest that PM2.5 collected in the Suwon traffic area has genotoxic effects and that reactive oxygen species may play a distinct role in these effects. In addition, aliphatic/chlorinated hydrocarbons, PAH/alkylderivatives, and nitro-PAH/ketones/quinones may be important causative agents of the genotoxic effects. [Copyright &y& Elsevier]

Abstract: Leather manufacturing has a high potential for environmental pollution due to hides and chemicals that are not completely absorbed during the tanning process. This study aims to investigate the mutagenic potential of surface water samples from Cadeia and Feitoria rivers (RS, Brazil) in areas influenced by tanneries and leather footwear industry. Micronucleus assays using V79 cells and human lymphocytes were used. Cells were exposed to surface water collected bimonthly from three sites for a year, totaling six samples. Significant MN induction in human lymphocytes was shown by 83% of samples from sites FEI001 and CAD001 located downstream from the industrial area, followed by FEI004 (33%), upstream. Only a single sample from site FEI004 showed a positive response for MN in V79 cells. Thirteen discordant and five concordant responses were found between the two in vitro tests. Mutagenic agents were found at the sites where chemical quality was worst, corroborating studies on chronic toxicity, oxidative stress and mutagenicity performed in this area. The assay using human lymphocytes was more sensitive than V79 cells to detect the contaminants from this area, showing that it is an excellent biomarker of environmental genotoxicity. [Copyright &y& Elsevier]

A safe alternative to the viral system used in gene therapy is a nonviral gene delivery system. Although polyethylenimine (PEI) and polyamidoamine (PAMAM) dendrimer are among the most promising gene-carrier candidates for efficient nonviral gene delivery, safety concerns regarding their toxicity remain. The aim of this study was to scrutinize the underlying mechanism of the cytotoxicity and genotoxicity of PEI (25 kDa) and PAMAM (G4). To our knowledge, this is the first study to explore the genotoxic effect of polymeric gene carriers. To evaluate cell death by PEI and PAMAM, we performed propidium-iodide staining and lactate-dehydrogenase release assays. The genotoxicity of the polymers was measured by comet assay and cytokinesis-block micronucleus assay. PEI- and PAMAM-treated groups induced both necrotic and apoptotic cell death. In the comet assay and micronuclei formation, significant increases in DNA damage were observed in both treatments. We conclude that PEI and PAMAM dendrimer can induce not only a relatively weak apoptotic and a strong necrotic effect, but also a moderate genotoxic effect. [ABSTRACT FROM AUTHOR]

Benzoyl peroxide (BPO) is one of the important oxidant compounds used as a free radical initiator in plastic production, as a bleaching agent in food and as a drug compound of acne treatment in cosmetic and pharmaceuticals industries. It is a progression agent in mouse skin carcinogenesis because it has tumor promoter activity and also strong cytotoxic activity. In this study, we have investigated the clastogenic effects of BPO with CBMN assay in human blood lymphocyte cultures. BPO at final concentrations of l0-5 M, 10-6 M, and 10-7 M was tested in peripheral bloods obtained from eight healthy male and eight female donors. According to data, the frequency of cells with micronuclei showed a statistically significant dose increase in a dependent manner compared with negative controls. Comparing the two donor groups, the differences in the mean counts were not significant. Increasing micronucleus rates showed that BPO could have clastogenic effect in human lymphocytes. [ABSTRACT FROM AUTHOR]

In the present study, we investigated whether genetic polymorphisms of metabolic enzymes in an exposed population were associated with genotoxic effects of the pollutants from e-waste in 58 subjects (the exposed) resided in a typical e-waste recycling site and 80 subjects (the controls) from a village away from the recycling site. Effects of genetic polymorphisms of glutathione S-transferases (GSTs) (GSTT1 and GSTM1) on the frequency of micronucleated binucleated cells (MNed BNC) in peripheral blood lymphocytes were evaluated. GSTM1 and GSTT1 were typed using PCR-restriction fragment length polymorphism methods. Cytogenetic alterations were evaluated using the cytokinesis-block micronucleus assay. The MNed BNC frequency was significantly higher in the exposed group (median: 4.0‰, IQR: 2.0-7.0‰) than in the control group (median: 1.0‰, IQR: 0.0-2.0‰, P < 0.01 for both comparisons); sera GST activities were also higher in the exposed subjects with either non-null GSTT1 (mean ± SD: 20.27 ± 6.43) or non-null GSTM1 (mean ± SD: 19.71 ± 4.89) than in the controls (mean ± SD: 18.79 ± 4.91 and 19.34 ± 6.42, respectively, P < 0.05 for both). Although the increased MNed BNC frequencies among the exposed group may be associated with the co-exposure of various chemical pollutants in the environment, there was no statistical evidence of an association between GSTs genotypes and frequencies of micronuclei in the study population. Because this study size was small, the mechanism of genotoxic effects caused by exposure to e-waste needs to be further validated in larger studies. [ABSTRACT FROM AUTHOR]

Abstract: This study addresses in vitro effects of raspberry (Rubus idaeus) seed extracts (RSE) on the frequency of micronuclei. We evaluated the effects of three different extracts (50%, 80%, and 100% methanol) in doses of 1.4, 4.2, and 8.4μg/mL, per 5mL culture using cytochalasin-B micronucleus (CBMN) assay in peripheral human lymphocytes. The frequency of MN was scored in binucleated (BN) cells. The nuclear proliferation index was also calculated. The distribution of polyphenolic compounds in RSEs was determined using LC/UV/ESI-TOF MS. The identified 37 compounds comprised flavanol monomers and oligomers, as well as varieties of ellagitannin components. Treatment of lymphocytes with RSEs induced a significant decrease in the frequency of micronuclei by 80%. These results demonstrate that the constituents of RSEs may be important in the prevention of oxidative lymphocyte damage by reactive oxygen species and may also reduce the level of DNA damage. These findings support the potential benefits of polyphenolic compounds from raspberry seeds as efficient antioxidants. [Copyright &y& Elsevier]