WorldWideScience

Sample records for genotoxicity critical considerations

  1. Genistein genotoxicity: Critical considerations of in vitro exposure dose

    International Nuclear Information System (INIS)

    Klein, Catherine B.; King, Audrey A.

    2007-01-01

    The potential health benefits of soy-derived phytoestrogens include their reported utility as anticarcinogens, cardioprotectants and as hormone replacement alternatives in menopause. Although there is increasing popularity of dietary phytoestrogen supplementation and of vegetarian and vegan diets among adolescents and adults, concerns about potential detrimental or other genotoxic effects persist. While a variety of genotoxic effects of phytoestrogens have been reported in vitro, the concentrations at which such effects occurred were often much higher than the physiologically relevant doses achievable by dietary or pharmacologic intake of soy foods or supplements. This review focuses on in vitro studies of the most abundant soy phytoestrogen, genistein, critically examining dose as a crucial determinant of cellular effects. In consideration of levels of dietary genistein uptake and bioavailability we have defined in vitro concentrations of genistein > 5 μM as non-physiological, and thus 'high' doses, in contrast to much of the previous literature. In doing so, many of the often-cited genotoxic effects of genistein, including apoptosis, cell growth inhibition, topoisomerase inhibition and others become less obvious. Recent cellular, epigenetic and microarray studies are beginning to decipher genistein effects that occur at dietarily relevant low concentrations. In toxicology, the well accepted principle of 'the dose defines the poison' applies to many toxicants and can be invoked, as herein, to distinguish genotoxic versus potentially beneficial in vitro effects of natural dietary products such as genistein

  2. Considerations on photochemical genotoxicity. II: Report of the 2009 International Workshop on Genotoxicity Testing Working Group

    NARCIS (Netherlands)

    Lynch, A.M.; Guzzie, P.J.; Bauer, D.; Gocke, E.; Itoh, S.; Jacobs, A.; Krul, C.A.M.; Schepky, A.; Tanaka, N.; Kasper, P.

    2011-01-01

    A workshop to reappraise the previous IWGT recommendations for photogenotoxicity testing [E. Gocke, L. Muller, P.J. Guzzie, S. Brendler-Schwaab, S. Bulera, C.F. Chignell, L.M. Henderson, A. Jacobs, H. Murli, R.D. Snyder, N. Tanaka, Considerations on photochemical genotoxicity: report of the

  3. Criticality safety and facility design considerations

    International Nuclear Information System (INIS)

    Waltz, W.R.

    1991-06-01

    Operations with fissile material introduce the risk of a criticality accident that may be lethal to nearby personnel. In addition, concerns over criticality safety can result in substantial delays and shutdown of facility operations. For these reasons, it is clear that the prevention of a nuclear criticality accident should play a major role in the design of a nuclear facility. The emphasis of this report will be placed on engineering design considerations in the prevention of criticality. The discussion will not include other important aspects, such as the physics of calculating limits nor criticality alarm systems

  4. Do Dental X-Rays Induce Genotoxicity and Cytotoxicity in Oral Mucosa Cells? A Critical Review.

    Science.gov (United States)

    Angelieri, Fernanda; Yujra, Veronica Quispe; Oshima, Celina Tizuko Fujiyama; Ribeiro, Daniel Araki

    2017-10-01

    Dental X-rays are widely used in clinical practice, since the technique is an important approach for diagnosing diseases in dental and periodontal tissues. However, it is widely known that radiation is capable of causing damage to cellular systems, such as genotoxicity or cytotoxicity. Thus, the aim of this review was to present a critical analysis regarding the studies published on genotoxicity and cytotoxicity induced by dental X-rays in oral mucosa cells. Such studies have revealed that some oral cell types are more sensitive than others following exposure to dental X-rays. Certainly, this review will contribute to a better understanding of this matter as well as to highlighting perspectives for further studies. Ultimately, such data will promote better safety for both patients and dental professionals. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  5. Methodological considerations for using umu assay to assess photo-genotoxicity of engineered nanoparticles

    DEFF Research Database (Denmark)

    Cupi, Denisa; Baun, Anders

    2016-01-01

    In this study we investigated the feasibility of high-throughput (96-well plate) umu assay to test the genotoxic effect of TiO2 engineered nanoparticles (ENPs) under UV light (full spectrum) and visible light (455nm). Exposure of TiO2 ENPs to up to 60min of UV light induced a photocatalytic...... production of ROS. However, UV light itself caused cytotoxic damage to Salmonella typhimurium at exposures >15min and a genotoxic effect at exposures >0.5min; and use of UV filters did not lower this effect. No genotoxicity of TiO2 ENPs was observed under visible light conditions at concentrations up to 100...

  6. ALARP considerations in criticality safety assessments

    International Nuclear Information System (INIS)

    Bowden, Russell L.; Barnes, Andrew; Thorne, Peter R.; Venner, Jack

    2003-01-01

    Demonstrating that the risk to the public and workers is As Low As Reasonably Practicable (ALARP) is a fundamental requirement of safety cases for nuclear facilities in the United Kingdom. This is embodied in the Safety Assessment Principles (SAPs) published by the Regulator, the essence of which is incorporated within the safety assessment processes of the various nuclear site licensees. The concept of ALARP within criticality safety assessments has taken some time to establish in the United Kingdom. In principle, the licensee is obliged to search for a deterministic criticality safety solution, such as safe geometry vessels and passive control features, rather than placing reliance on active measurement devices and plant administrative controls. This paper presents a consideration of some ALARP issues in relation to the development of criticality safety cases. The paper utilises some idealised examples covering a range of issues facing the criticality safety assessor, including new plant design, operational plant and decommissioning activities. These examples are used to outline the elements of the criticality safety cases and present a discussion of ALARP in the context of criticality safety assessments. (author)

  7. Approaches to the risk assessment of genotoxic carcinogens in food: a critical appraisal.

    Science.gov (United States)

    O'Brien, J; Renwick, A G; Constable, A; Dybing, E; Müller, D J G; Schlatter, J; Slob, W; Tueting, W; van Benthem, J; Williams, G M; Wolfreys, A

    2006-10-01

    The present paper examines the particular difficulties presented by low levels of food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to eliminate completely from the diet, and proposes a structured approach for the evaluation of such compounds. While the ALARA approach is widely applicable to all substances in food that are both carcinogenic and genotoxic, it does not take carcinogenic potency into account and, therefore, does not permit prioritisation based on potential risk or concern. In the absence of carcinogenicity dose-response data, an assessment based on comparison with an appropriate threshold of toxicological concern may be possible. When carcinogenicity data from animal bioassays are available, a useful analysis is achieved by the calculation of margins of exposure (MOEs), which can be used to compare animal potency data with human exposure scenarios. Two reference points on the dose-response relationship that can be used for MOE calculation were examined; the T25 value, which is derived from linear extrapolation, and the BMDL10, which is derived from mathematical modelling of the dose-response data. The above approaches were applied to selected food-borne genotoxic carcinogens. The proposed approach is applicable to all substances in food that are DNA-reactive genotoxic carcinogens and enables the formulation of appropriate semi-quantitative advice to risk managers.

  8. Approaches to the risk assessment of genotoxic carcinogens in food: a critical appraisal.

    NARCIS (Netherlands)

    O'Brien, J; Renwick, A G; Constable, A; Dybing, Erik; Müller, D J G; Schlatter, J; Slob, Wout; Tueting, W; Benthem, Jan van; Williams, G M; Wolfreys, A

    2006-01-01

    The present paper examines the particular difficulties presented by low levels of food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to eliminate completely from the diet, and proposes a structured approach for the evaluation of such compounds. While the ALARA approach is

  9. Critical effective methods to detect genotoxic carcinogens and neoplasm-promoting agents.

    OpenAIRE

    Weisburger, J H; Williams, G M

    1991-01-01

    Neoplasia in fish can result from contamination of waters with carcinogens and promoters. Cancer in fish, therefore, is a possible indicator of cancer risk to man and serves as a guide to the need for preventive approaches involving improved means of waste disposal and environmental hygiene. Moreover, cancer in fish indicates that this important food source may be contaminated. Detection of genotoxic carcinogens to which fish are exposed can be achieved quickly and efficiently by carefully se...

  10. Critical effective methods to detect genotoxic carcinogens and neoplasm-promoting agents.

    Science.gov (United States)

    Weisburger, J H; Williams, G M

    1991-01-01

    Neoplasia in fish can result from contamination of waters with carcinogens and promoters. Cancer in fish, therefore, is a possible indicator of cancer risk to man and serves as a guide to the need for preventive approaches involving improved means of waste disposal and environmental hygiene. Moreover, cancer in fish indicates that this important food source may be contaminated. Detection of genotoxic carcinogens to which fish are exposed can be achieved quickly and efficiently by carefully selected batteries of complementary in vitro and in vivo bioassays. One such battery consists of the Ames test, a reverse mutation assay in prokaryotic Salmonella typhimurium, and the Williams test, involving DNA repair in freshly explanted metabolically highly competent liver cells from diverse species, including humans. Determination of DNA-carcinogen adducts by varied techniques, including 32P-postlabeling, as well as DNA breakage, mammalian cell mutagenicity, chromosome aberrations, sister chromatid exchange, or cell transformation represent additional approaches, each with its own advantages and disadvantages. More research is needed on systems to apprehend neoplasm promoters, but tests to determine interruption of intercellular communications through gap junctions appear promising. Other approaches rely on measurement of enzymes such as ornithine decarboxylase and protein kinase C. Approaches to the definition of risk to fish or humans require characterization of the genotoxic or nongenotoxic properties of a chemical, relative potency data obtained in select, limited rodent bioassays, and knowledge of prevailing environmental concentrations of specific carcinogens.

  11. Consideration of criticality in a nuclear waste repository

    International Nuclear Information System (INIS)

    Rechard, R.P.; Sanchez, L.C.; Stockman, C.T.; Ramsey, J.L. Jr.; Martell, M.

    1995-01-01

    The preliminary criticality analysis that was done suggests that the possibility of achieving critical conditions cannot be easily ruled out without looking at the geochemical process of assembly or the dynamics of the operation of a critical assembly. The evaluation of a critical assembly requires an integrated, consistent approach that includes evaluating the following: (1) the alteration rates of the layers of the container and spent fuel, (2) the transport of fissile material or neutron absorbers, and (3) the assembly mechanisms that can achieve critical conditions. The above is a non-trivial analysis and preliminary work suggests that with the loading assumed, enough fissile mass will leach from the HEU multi-purpose canisters to support a criticality. In addition, the consequences of an unpressurized Oklo type criticality would be insignificant to the performance of an unsaturated, tuff repository

  12. Regulatory considerations for computational requirements for nuclear criticality safety

    International Nuclear Information System (INIS)

    Bidinger, G.H.

    1995-01-01

    As part of its safety mission, the U.S. Nuclear Regulatory Commission (NRC) approves the use of computational methods as part of the demonstration of nuclear criticality safety. While each NRC office has different criteria for accepting computational methods for nuclear criticality safety results, the Office of Nuclear Materials Safety and Safeguards (NMSS) approves the use of specific computational methods and methodologies for nuclear criticality safety analyses by specific companies (licensees or consultants). By contrast, the Office of Nuclear Reactor Regulation approves codes for general use. Historically, computational methods progressed from empirical methods to one-dimensional diffusion and discrete ordinates transport calculations and then to three-dimensional Monte Carlo transport calculations. With the advent of faster computational ability, three-dimensional diffusion and discrete ordinates transport calculations are gaining favor. With the proper user controls, NMSS has accepted any and all of these methods for demonstrations of nuclear criticality safety

  13. Criticality safety considerations. Integral Monitored Retrievable Storage (MRS) Facility

    International Nuclear Information System (INIS)

    1986-09-01

    This report summarizes the criticality analysis performed to address criticality safety concerns and to support facility design during the conceptual design phase of the Monitored Retrievable Storage (MRS) Facility. The report addresses the criticality safety concerns, the design features of the facility relative to criticality, and the results of the analysis of both normal operating and hypothetical off-normal conditions. Key references are provided (Appendix C) if additional information is desired by the reader. The MRS Facility design was developed and the related analysis was performed in accordance with the MRS Facility Functional Design Criteria and the Basis for Design. The detailed description and calculations are documented in the Integral MRS Facility Conceptual Design Report. In addition to the summary portion of this report, explanatary notes for various terms, calculation methodology, and design parameters are presented in Appendix A. Appendix B provides a brief glossary of technical terms

  14. Leading to Transgress: Critical Considerations for Transforming Leadership Learning.

    Science.gov (United States)

    Osteen, Laura; Guthrie, Kathy L; Jones, Tamara Bertrand

    2016-12-01

    The culturally relevant leadership learning (CRLL) model is explored through the lens of theory and practice. This creates critical questions to guide leadership educators in the ongoing process of transforming leadership programs. © 2016 Wiley Periodicals, Inc., A Wiley Company.

  15. Design and criticality considerations for 9977 and 9978 shipping packages

    International Nuclear Information System (INIS)

    Reed, R.; Biswas, D.; Abramczyk, G.

    2009-01-01

    Savannah River National Laboratory (SRNL) has developed two new, Type B, state-of-the-art, general purpose, fissile material Shipping Packages, designated as 9977 and 9978, as replacements for the U.S. Dept. of Transportation (DOT) specification 6M container. The packages accommodate plutonium, uranium, and other special nuclear materials in bulk quantities and in many forms with capabilities exceeding those of the 6M. A nuclear criticality safety evaluation demonstrates the safe configurations of the new shipping container for plutonium and uranium metal/oxide loading under various conditions for the Safety Analysis Report for Packaging (SARP). The evaluation is in compliance with the performance requirements of 10CFR 71, specifically 10CFR71.55 and 71.59. The criticality safety index (CSI) is 1.0 for most of the contents (Max. Pu Loading -4.4 kg). (authors)

  16. A critical consideration of ethical foundations for the accounting profession

    OpenAIRE

    Buys, Pieter; Visser, Susan; Oberholzer, Merwe

    2012-01-01

    When considering some of the key reasons for the desperate state of the current global economic environment, it is difficult to deny accounting's role therein. Although accounting institutes require adherence to codes of conduct, the question remains as to what happened to the stewardship function of the accounting profession. This article has critically reflected on the question, 'What constitutes an ethical accounting profession'? The key principles within many institutes' codes of conduct,...

  17. Critical issues with the in vivo comet assay: A report of the comet assay working group in the 6th International Workshop on Genotoxicity Testing (IWGT).

    Science.gov (United States)

    Speit, Günter; Kojima, Hajime; Burlinson, Brian; Collins, Andrew R; Kasper, Peter; Plappert-Helbig, Ulla; Uno, Yoshifumi; Vasquez, Marie; Beevers, Carol; De Boeck, Marlies; Escobar, Patricia A; Kitamoto, Sachiko; Pant, Kamala; Pfuhler, Stefan; Tanaka, Jin; Levy, Dan D

    2015-05-01

    As a part of the 6th IWGT, an expert working group on the comet assay evaluated critical topics related to the use of the in vivo comet assay in regulatory genotoxicity testing. The areas covered were: identification of the domain of applicability and regulatory acceptance, identification of critical parameters of the protocol and attempts to standardize the assay, experience with combination and integration with other in vivo studies, demonstration of laboratory proficiency, sensitivity and power of the protocol used, use of different tissues, freezing of samples, and choice of appropriate measures of cytotoxicity. The standard protocol detects various types of DNA lesions but it does not detect all types of DNA damage. Modifications of the standard protocol may be used to detect additional types of specific DNA damage (e.g., cross-links, bulky adducts, oxidized bases). In addition, the working group identified critical parameters that should be carefully controlled and described in detail in every published study protocol. In vivo comet assay results are more reliable if they were obtained in laboratories that have demonstrated proficiency. This includes demonstration of adequate response to vehicle controls and an adequate response to a positive control for each tissue being examined. There was a general agreement that freezing of samples is an option but more data are needed in order to establish generally accepted protocols. With regard to tissue toxicity, the working group concluded that cytotoxicity could be a confounder of comet results. It is recommended to look at multiple parameters such as histopathological observations, organ-specific clinical chemistry as well as indicators of tissue inflammation to decide whether compound-specific toxicity might influence the result. The expert working group concluded that the alkaline in vivo comet assay is a mature test for the evaluation of genotoxicity and can be recommended to regulatory agencies for use

  18. Criticality safety considerations for MSRE fuel drain tank uranium aggregation

    International Nuclear Information System (INIS)

    Hollenbach, D.F.; Hopper, C.M.

    1997-01-01

    This paper presents the results of a preliminary criticality safety study of some potential effects of uranium reduction and aggregation in the Molten Salt Reactor Experiment (MSRE) fuel drain tanks (FDTs) during salt removal operations. Since the salt was transferred to the FDTs in 1969, radiological and chemical reactions have been converting the uranium and fluorine in the salt to UF 6 and free fluorine. Significant amounts of uranium (at least 3 kg) and fluorine have migrated out of the FDTs and into the off-gas system (OGS) and the auxiliary charcoal bed (ACB). The loss of uranium and fluorine from the salt changes the chemical properties of the salt sufficiently to possibly allow the reduction of the UF 4 in the salt to uranium metal as the salt is remelted prior to removal. It has been postulated that up to 9 kg of the maximum 19.4 kg of uranium in one FDT could be reduced to metal and concentrated. This study shows that criticality becomes a concern when more than 5 kg of uranium concentrates to over 8 wt% of the salt in a favorable geometry

  19. A critical consideration of ethical foundations for the accounting profession

    Directory of Open Access Journals (Sweden)

    Pieter Buys

    2012-11-01

    Full Text Available When considering some of the key reasons for the desperate state of the current global economic environment, it is difficult to deny accounting’s role therein. Although accounting institutes require adherence to codes of conduct, the question remains as to what happened to the stewardship function of the accounting profession. This article has critically reflected on the question, ‘What constitutes an ethical accounting profession’? The key principles within many institutes’ codes of conduct, such as competency, integrity, objectivity and confidentiality, have been considered against the background of utilitarianism, formalism and virtue ethics as foundational ethical theories. This article has concluded that although these principles aim to provide a framework for ethical accounting conduct, individual subjectivity on the part of the accountant will play a role in how these ethical principles become ethical practices.

  20. Transcriptional upregulation of p19INK4d upon diverse genotoxic stress is critical for optimal DNA damage response.

    Science.gov (United States)

    Ceruti, Julieta M; Scassa, María E; Marazita, Mariela C; Carcagno, Abel C; Sirkin, Pablo F; Cánepa, Eduardo T

    2009-06-01

    p19INK4d promotes survival of several cell lines after UV irradiation due to enhanced DNA repair, independently of CDK4 inhibition. To further understand the action of p19INK4d in the cellular response to DNA damage, we aimed to elucidate whether this novel regulator plays a role only in mechanisms triggered by UV or participates in diverse mechanisms initiated by different genotoxics. We found that p19INK4d is induced in cells injured with cisplatin or beta-amyloid peptide as robustly as with UV. The mentioned genotoxics transcriptionally activate p19INK4d expression as demonstrated by run-on assay without influencing its mRNA stability and with partial requirement of protein synthesis. It is not currently known whether DNA damage-inducible genes are turned on by the DNA damage itself or by the consequences of that damage. Experiments carried out in cells transfected with distinct damaged DNA structures revealed that the damage itself is not responsible for the observed up-regulation. It is also not known whether the increased expression of DNA-damage-inducible genes is related to immediate protective responses such as DNA repair or to more delayed responses such as cell cycle arrest or apoptosis. We found that ectopic expression of p19INK4d improves DNA repair ability and protects neuroblastoma cells from apoptosis caused by cisplatin or beta-amyloid peptide. Using clonal cell lines where p19INK4d levels can be modified at will, we show that p19INK4d expression correlates with increased survival and clonogenicity. The results presented here, prompted us to suggest that p19INK4d displays an important role in an early stage of cellular DNA damage response.

  1. Consideration of critical heat flux margin prediction by subcooled or low quality critical heat flux correlations

    International Nuclear Information System (INIS)

    Hejzlar, P.; Todreas, N.E.

    1996-01-01

    The accurate prediction of the critical heat flux (CHF) margin which is a key design parameter in a variety of cooling and heating systems is of high importance. These margins are, for the low quality region, typically expressed in terms of critical heat flux ratios using the direct substitution method. Using a simple example of a heated tube, it is shown that CHF correlations of a certain type often used to predict CHF margins, expressed in this manner, may yield different results, strongly dependent on the correlation in use. It is argued that the application of the heat balance method to such correlations, which leads to expressing the CHF margins in terms of the critical power ratio, may be more appropriate. (orig.)

  2. In silico prediction of genotoxicity.

    Science.gov (United States)

    Wichard, Jörg D

    2017-08-01

    The in silico prediction of genotoxicity has made considerable progress during the last years. The main driver for the pharmaceutical industry is the ICH M7 guideline about the assessment of DNA reactive impurities. An important component of this guideline is the use of in silico models as an alternative approach to experimental testing. The in silico prediction of genotoxicity provides an established and accepted method that defines the first step in the assessment of DNA reactive impurities. This was made possible by the growing amount of reliable Ames screening data, the attempts to understand the activity pathways and the subsequent development of computer-based prediction systems. This paper gives an overview of how the in silico prediction of genotoxicity is performed under the ICH M7 guideline. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Recovery from chemical, biological, and radiological incidents. Critical infrastructure and economic impact considerations

    Energy Technology Data Exchange (ETDEWEB)

    Franco, David Oliver [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Yang, Lynn I. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Hammer, Ann E. [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

    2012-06-01

    To restore regional lifeline services and economic activity as quickly as possible after a chemical, biological or radiological incident, emergency planners and managers will need to prioritize critical infrastructure across many sectors for restoration. In parallel, state and local governments will need to identify and implement measures to promote reoccupation and economy recovery in the region. This document provides guidance on predisaster planning for two of the National Disaster Recovery Framework Recovery Support Functions: Infrastructure Systems and Economic Recovery. It identifies key considerations for infrastructure restoration, outlines a process for prioritizing critical infrastructure for restoration, and identifies critical considerations for promoting regional economic recovery following a widearea disaster. Its goal is to equip members of the emergency preparedness community to systematically prioritize critical infrastructure for restoration, and to develop effective economic recovery plans in preparation for a widearea CBR disaster.

  4. Critical review of the current and future challenges associated with advanced in vitro systems towards the study of nanoparticle (secondary) genotoxicity.

    Science.gov (United States)

    Evans, Stephen J; Clift, Martin J D; Singh, Neenu; de Oliveira Mallia, Jefferson; Burgum, Michael; Wills, John W; Wilkinson, Thomas S; Jenkins, Gareth J S; Doak, Shareen H

    2017-01-01

    With the need to understand the potential biological impact of the plethora of nanoparticles (NPs) being manufactured for a wide range of potential human applications, due to their inevitable human exposure, research activities in the field of NP toxicology has grown exponentially over the last decade. Whilst such increased research efforts have elucidated an increasingly significant knowledge base pertaining to the potential human health hazard posed by NPs, understanding regarding the possibility for NPs to elicit genotoxicity is limited. In vivo models are unable to adequately discriminate between the specific modes of action associated with the onset of genotoxicity. Additionally, in line with the recent European directives, there is an inherent need to move away from invasive animal testing strategies. Thus, in vitro systems are an important tool for expanding our mechanistic insight into NP genotoxicity. Yet uncertainty remains concerning their validity and specificity for this purpose due to the unique challenges presented when correlating NP behaviour in vitro and in vivo This review therefore highlights the current state of the art in advanced in vitro systems and their specific advantages and disadvantages from a NP genotoxicity testing perspective. Key indicators will be given related to how these systems might be used or improved to enhance understanding of NP genotoxicity. © The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society.

  5. Critical considerations when planning experimental in vivo studies in dental traumatology.

    Science.gov (United States)

    Andreasen, Jens O; Andersson, Lars

    2011-08-01

    In vivo studies are sometimes needed to understand healing processes after trauma. For several reasons, not the least ethical, such studies have to be carefully planned and important considerations have to be taken into account about suitability of the experimental model, sample size and optimizing the accuracy of the analysis. Several manuscripts of in vivo studies are submitted for publication to Dental Traumatology and rejected because of inadequate design, methodology or insufficient documentation of the results. The authors have substantial experience in experimental in vivo studies of tissue healing in dental traumatology and share their knowledge regarding critical considerations when planning experimental in vivo studies. © 2011 John Wiley & Sons A/S.

  6. Critical considerations for the application of environmental DNA methods to detect aquatic species

    Science.gov (United States)

    Goldberg, Caren S.; Turner, Cameron R.; Deiner, Kristy; Klymus, Katy E.; Thomsen, Philip Francis; Murphy, Melanie A.; Spear, Stephen F.; McKee, Anna; Oyler-McCance, Sara J.; Cornman, Robert S.; Laramie, Matthew B.; Mahon, Andrew R.; Lance, Richard F.; Pilliod, David S.; Strickler, Katherine M.; Waits, Lisette P.; Fremier, Alexander K.; Takahara, Teruhiko; Herder, Jelger E.; Taberlet, Pierre

    2016-01-01

    Species detection using environmental DNA (eDNA) has tremendous potential for contributing to the understanding of the ecology and conservation of aquatic species. Detecting species using eDNA methods, rather than directly sampling the organisms, can reduce impacts on sensitive species and increase the power of field surveys for rare and elusive species. The sensitivity of eDNA methods, however, requires a heightened awareness and attention to quality assurance and quality control protocols. Additionally, the interpretation of eDNA data demands careful consideration of multiple factors. As eDNA methods have grown in application, diverse approaches have been implemented to address these issues. With interest in eDNA continuing to expand, supportive guidelines for undertaking eDNA studies are greatly needed.Environmental DNA researchers from around the world have collaborated to produce this set of guidelines and considerations for implementing eDNA methods to detect aquatic macroorganisms.Critical considerations for study design include preventing contamination in the field and the laboratory, choosing appropriate sample analysis methods, validating assays, testing for sample inhibition and following minimum reporting guidelines. Critical considerations for inference include temporal and spatial processes, limits of correlation of eDNA with abundance, uncertainty of positive and negative results, and potential sources of allochthonous DNA.We present a synthesis of knowledge at this stage for application of this new and powerful detection method.

  7. Scientific Opinion on Flavouring Group Evaluation 210 Revision 2 (FGE.210Rev2): Consideration of genotoxic potential for α,β-unsaturated alicyclic ketones and precursors from chemical subgroup 2.4 of FGE.19

    DEFF Research Database (Denmark)

    Beltoft, Vibe Meister; Nørby, Karin Kristiane

    Safety Authority was requested to evaluate the genotoxic potential of 14 flavouring substances in Flavouring Group Evaluation 210 (FGE.210). In FGE.210, the Panel concluded that the genotoxic potential could not be ruled out for any of the flavouring substances. In FGE.210 Revision1, the Panel co...

  8. Some critical considerations on the present epistemological and scientific debate on quantum mechanics

    International Nuclear Information System (INIS)

    Ghirardi, G.C.

    1985-09-01

    Some general methodological considerations aimed to guarantee the necessary logical rigor to the present debate on quantum mechanics are presented. In particular some misunderstandings about the implications of the critical analysis put forward by Einstein, Podolsky and Rosen (EPR) which can be found in the literature, are discussed. These misunderstandings are shown to arise from possible underestimates, overestimates and misinterpretations of the EPR argument. It is argued that the difficulties pointed out by EPR are, in a sense that will be defined precisely, unavoidable. A model which tries to solve the difficulties arising from quantum non separability effects when macroscopic systems are involved, is briefly sketched. (author)

  9. A predictive toxicogenomics signature to classify genotoxic versus non-genotoxic chemicals in human TK6 cells

    Directory of Open Access Journals (Sweden)

    Andrew Williams

    2015-12-01

    Full Text Available Genotoxicity testing is a critical component of chemical assessment. The use of integrated approaches in genetic toxicology, including the incorporation of gene expression data to determine the DNA damage response pathways involved in response, is becoming more common. In companion papers previously published in Environmental and Molecular Mutagenesis, Li et al. (2015 [6] developed a dose optimization protocol that was based on evaluating expression changes in several well-characterized stress-response genes using quantitative real-time PCR in human lymphoblastoid TK6 cells in culture. This optimization approach was applied to the analysis of TK6 cells exposed to one of 14 genotoxic or 14 non-genotoxic agents, with sampling 4 h post-exposure. Microarray-based transcriptomic analyses were then used to develop a classifier for genotoxicity using the nearest shrunken centroids method. A panel of 65 genes was identified that could accurately classify toxicants as genotoxic or non-genotoxic. In Buick et al. (2015 [1], the utility of the biomarker for chemicals that require metabolic activation was evaluated. In this study, TK6 cells were exposed to increasing doses of four chemicals (two genotoxic that require metabolic activation and two non-genotoxic chemicals in the presence of rat liver S9 to demonstrate that S9 does not impair the ability to classify genotoxicity using this genomic biomarker in TK6cells.

  10. Scientific Opinion on Flavouring Group Evaluation 220 Revision 3 (FGE.220Rev3): Consideration of genotoxic potential for α,β-unsaturated 3(2H)-Furanones from subgroup 4.4 of FGE.19

    DEFF Research Database (Denmark)

    Beltoft, Vibe Meister; Nørby, Karin Kristiane

    The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate the genotoxic potential of 10 flavouring substances from FGE.19 subgroup 4.4, in the Flavouring Group Evaluation 220 (FGE.220). FGE.220 is subdivided...... into two subgroups: subgroup 4.4a containing [FL-no: 13.089, 13.117, 13.119, 13.157 and 13.175] and subgroup 4.4b containing [13.010, 13.084 and 13.085, 13.099 and 13.176]. For both subgroups the Panel concluded that the genotoxicity alert could not be ruled out based on the data available and accordingly...... additional genotoxicity data were requested. In FGE.220, Revision 1, the Panel concluded that for the substances in subgroup 4.4b there is no concern for genotoxicity. In FGE.220, Revision 2, the Panel evaluated genotoxicity studies on two representative substances of subgroup 4.4a: 2,5-dimethylfuran-3(2H...

  11. Considerations of critical quality attributes in the analytical comparability assessment of biosimilar products.

    Science.gov (United States)

    Kwon, Ohseok; Joung, Jeewon; Park, Younjoo; Kim, Chan Wha; Hong, Seung Hwa

    2017-07-01

    Based on experience in clinical trial approvals and marketing authorizations for biosimilar products in Korea, we suggest principles for the analytical comparability assessment of biosimilar products with respect to regulatory considerations. The composition and manufacturing processes of biosimilar products can differ from those of the reference product depending on the information available for the reference product and the time of product development; however, the analytical characteristics of biosimilar products should be highly similar to those of the reference product. Although manufacturing an identical product in terms of the quality profile is nearly impossible due to the high molecular weight and complex structure of biological products, the developer of the biosimilar product should attempt to establish a quality level as similar to that of the reference product as possible. When comparing the similarity of quality attributes, the criticality of the quality attributes and the characteristics of orthogonal quality attributes need to be considered carefully. Based on the results from the analytical comparability assessment, the comparability results of non-clinical and clinical studies should be evaluated before claiming biosimilarity to the reference product. In this review, we focus on quality attribute evaluation based on our regulatory experience. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  12. Consideration of Nuclear Criticality When Directly Disposing Highly Enriched Spent Nuclear Fuel in Unsaturated Tuff - I: Nuclear Criticality Constraints

    International Nuclear Information System (INIS)

    Rechard, Rob P.; Sanchez, Lawrence C.; Trellue, Holly R.

    2003-01-01

    This paper presents the mass, concentration, and volume required for a critical event to occur in homogeneous mixtures of fissile material and various other geologic materials. The fissile material considered is primarily highly enriched uranium spent fuel; however, 239 Pu is considered in some cases. The non-fissile materials examined are those found in the proposed repository area at Yucca Mountain, Nevada: volcanic tuff, iron rust, concrete, and naturally occurring water. For 235 U, the minimum critical solid concentration for tuff was 5 kg/m 3 (similar to sandstone), and in goethite, 45 kg/m 3 . The critical mass of uranium was sensitive to a number of factors, such as moisture content and fissile enrichment, but had a minimum, assuming almost 100% saturation and >20% enrichment, of 18 kg in tuff as Soddyite (or 9.5 kg as UO 2 ) and 7 kg in goethite. For 239 Pu, the minimum critical solid concentration for tuff was 3 kg/m 3 (similar to sandstone); in goethite, 20 kg/m 3 . The critical mass of plutonium was also sensitive to a number of factors, but had a minimum, assuming 100% saturation and 80-90% enrichment, of 5 kg in tuff and 6 kg in goethite

  13. Genotoxicity of swine effluents.

    Science.gov (United States)

    Techio, V H; Stolberg, J; Kunz, A; Zanin, E; Perdomo, C C

    2011-01-01

    This study aimed at the investigation of genotoxic effects of swine effluents from different stages of a treatment system for swine wastes through bioassay of stamen hairs and micronuclei in Tradescantia (clone BNL 4430). No significant differences (p≥0.05) regarding the genic mutations were found in the bioassay of stamen hairs, independently of the effluent analysed. For the genotoxicity test with micronuclei, the plants exposed to raw wastes, to sludge, and to effluent of the biodigester have presented higher rates of chromosomal damages (micronuclei), with significant differences in relation to the control group and other effluent of the waste treatment system (p≤0.05). The association between the chemical parameters and the genotoxicity data have shown that the variables COD and TKN have presented significant correlation (p≤0.05) with the number of mutagenic events in the tetrads.

  14. Genotoxicity of metal nanoparticles.

    Science.gov (United States)

    Xie, Hong; Mason, Michael M; Wise, John Pierce

    2011-01-01

    Nanotechnology is currently used in industry, medicine, and military applications, as well as in more than 300 commercial products. Yet, the same properties that make these particles exciting for technology also make them daunting public health concerns because their toxicity is unknown and relatively unexplored. Increased attention is being placed on the study of metal particle genotoxicity; however, a lot of unknowns remain about their effects and the mechanisms. In this article, we highlight some metal and metal oxide nanoparticles of interest and discuss the current in vivo and in vitro studies of genotoxic effects. Many metal nanoparticles were found to cause chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. Inconsistencies are found in the literature, however, thus drawing conclusions is difficult due to a variety of factors. Therefore, the areas requiring further attention are highlighted and recommendations to improve our understanding of the genotoxic potential are addressed.

  15. Genotoxic effect of alkaloids

    Directory of Open Access Journals (Sweden)

    J. A. P. Henriques

    1991-01-01

    Full Text Available Because of the increase use of alkaloids in general medical practice in recent years, it is of interest to determine genotoxic, mutagenic and recombinogenic response to different groups of alkaloids in prokaryotic and eucaryotic organisms. Reserpine, boldine and chelerythrine did not show genotoxicity response in the SOS-Chromotest whereas skimmianine showed genotixicity in the presence of a metabolic activation mixture. Voacristine isolated fromthe leaves of Ervatamia coronaria shows in vivo cytostatic and mutagenic effects in Saccharomyces cerevisiae hapioids cells. The Rauwolfia alkaloid (reserpine was not able to induce reverse mutation and recombinational mitotic events (crossing-over and gene conversion in yeast diploid strain XS2316.

  16. Consideration of nuclear criticality when disposing of transuranic waste at the Waste Isolation Pilot Plant

    Energy Technology Data Exchange (ETDEWEB)

    RECHARD,ROBERT P.; SANCHEZ,LAWRENCE C.; STOCKMAN,CHRISTINE T.; TRELLUE,HOLLY R.

    2000-04-01

    Based on general arguments presented in this report, nuclear criticality was eliminated from performance assessment calculations for the Waste Isolation Pilot Plant (WIPP), a repository for waste contaminated with transuranic (TRU) radioisotopes, located in southeastern New Mexico. At the WIPP, the probability of criticality within the repository is low because mechanisms to concentrate the fissile radioisotopes dispersed throughout the waste are absent. In addition, following an inadvertent human intrusion into the repository (an event that must be considered because of safety regulations), the probability of nuclear criticality away from the repository is low because (1) the amount of fissile mass transported over 10,000 yr is predicted to be small, (2) often there are insufficient spaces in the advective pore space (e.g., macroscopic fractures) to provide sufficient thickness for precipitation of fissile material, and (3) there is no credible mechanism to counteract the natural tendency of the material to disperse during transport and instead concentrate fissile material in a small enough volume for it to form a critical concentration. Furthermore, before a criticality would have the potential to affect human health after closure of the repository--assuming that a criticality could occur--it would have to either (1) degrade the ability of the disposal system to contain nuclear waste or (2) produce significantly more radioisotopes than originally present. Neither of these situations can occur at the WIPP; thus, the consequences of a criticality are also low.

  17. Consideration of nuclear criticality when disposing of transuranic waste at the Waste Isolation Pilot Plant

    International Nuclear Information System (INIS)

    Rechard, Robert P.; Sanchez, Lawrence C.; Stockman, Christine T.; Trellue, Holly R.

    2000-01-01

    Based on general arguments presented in this report, nuclear criticality was eliminated from performance assessment calculations for the Waste Isolation Pilot Plant (WIPP), a repository for waste contaminated with transuranic (TRU) radioisotopes, located in southeastern New Mexico. At the WIPP, the probability of criticality within the repository is low because mechanisms to concentrate the fissile radioisotopes dispersed throughout the waste are absent. In addition, following an inadvertent human intrusion into the repository (an event that must be considered because of safety regulations), the probability of nuclear criticality away from the repository is low because (1) the amount of fissile mass transported over 10,000 yr is predicted to be small, (2) often there are insufficient spaces in the advective pore space (e.g., macroscopic fractures) to provide sufficient thickness for precipitation of fissile material, and (3) there is no credible mechanism to counteract the natural tendency of the material to disperse during transport and instead concentrate fissile material in a small enough volume for it to form a critical concentration. Furthermore, before a criticality would have the potential to affect human health after closure of the repository--assuming that a criticality could occur--it would have to either (1) degrade the ability of the disposal system to contain nuclear waste or (2) produce significantly more radioisotopes than originally present. Neither of these situations can occur at the WIPP; thus, the consequences of a criticality are also low

  18. Safety considerations of new critical assembly for the Research Reactor Institute, Kyoto University

    International Nuclear Information System (INIS)

    Umeda, Iwao; Matsuoka, Naomi; Harada, Yoshihiko; Miyamoto, Keiji; Kanazawa, Takashi

    1975-01-01

    The new critical assembly type of nuclear reactor having three cores for the first time in the world was completed successfully at the Research Reactor Institute of Kyoto University in autumn of 1974. It is called KUCA (Kyoto University Critical Assembly). Safety of the critical assembly was considered sufficiently in consequence of discussions between the researchers of the institute and the design group of our company, and then many bright ideas were created through the discussions. This paper is described the new safety design of main equipments - oil pressure type center core drive mechanism, removable water overflow mechanism, core division mechanism, control rod drive mechansim, protection instrumentation system and interlock key system - for the critical assembly. (author)

  19. Critical considerations when planning experimental in vivo studies in dental traumatology

    DEFF Research Database (Denmark)

    Andreasen, Jens O; Andersson, Lars

    2011-01-01

    In vivo studies are sometimes needed to understand healing processes after trauma. For several reasons, not the least ethical, such studies have to be carefully planned and important considerations have to be taken into account about suitability of the experimental model, sample size and optimizing...

  20. Consideration of critically when directly disposing highly enriched spent nuclear fuel in unsaturated tuff: Bounding estimates

    International Nuclear Information System (INIS)

    Rechard, R.P.; Tierney, M.S.; Sanchez, L.C.; Martell, M.-A.

    1996-05-01

    This report presents one of 2 approaches (bounding calculations) which were used in a 1994 study to examine the possibility of a criticality in a repository. Bounding probabilities, although rough, point to the difficulty of creating conditions under which a critical mass could be assembled (container corrosion, separation of neutron absorbers from fissile material, collapse or precipitation of fissile material) and how significant the geochemical and hydrologic phenomena are. The study could not conceive of a mechanism consistent with conditions under which an atomic explosion could occur. Should a criticality occur in or near a container in the future, boundary consequence calculations showed that fissions from one critical event ( 20 fissions, if similar to aqueous and metal accidents and experiments) are quite small compared to the amount of fissions represented by the spent fuel itself. If it is assumed that the containers necessary to hold the highly enriched spent fuel went critical once per day for 1 million years, creating an energy release of about 10 20 fissions, the number of fissions equals about 10 28 , which corresponds to only 1% of the fission inventory in a repository containing 70,000 metric tons of heavy metal, the expected size for the proposed repository at Yucca Mountain, Nevada

  1. Consideration of critically when directly disposing highly enriched spent nuclear fuel in unsaturated tuff: Bounding estimates

    Energy Technology Data Exchange (ETDEWEB)

    Rechard, R.P.; Tierney, M.S.; Sanchez, L.C.; Martell, M.-A.

    1996-05-01

    This report presents one of 2 approaches (bounding calculations) which were used in a 1994 study to examine the possibility of a criticality in a repository. Bounding probabilities, although rough, point to the difficulty of creating conditions under which a critical mass could be assembled (container corrosion, separation of neutron absorbers from fissile material, collapse or precipitation of fissile material) and how significant the geochemical and hydrologic phenomena are. The study could not conceive of a mechanism consistent with conditions under which an atomic explosion could occur. Should a criticality occur in or near a container in the future, boundary consequence calculations showed that fissions from one critical event (<10{sup 20} fissions, if similar to aqueous and metal accidents and experiments) are quite small compared to the amount of fissions represented by the spent fuel itself. If it is assumed that the containers necessary to hold the highly enriched spent fuel went critical once per day for 1 million years, creating an energy release of about 10{sup 20} fissions, the number of fissions equals about 10{sup 28}, which corresponds to only 1% of the fission inventory in a repository containing 70,000 metric tons of heavy metal, the expected size for the proposed repository at Yucca Mountain, Nevada.

  2. Considerations in the construction of an instrument to assess attitudes regarding critical illness gene variation research.

    Science.gov (United States)

    Freeman, Bradley D; Kennedy, Carie R; Bolcic-Jankovic, Dragana; Eastman, Alexander; Iverson, Ellen; Shehane, Erica; Celious, Aaron; Barillas, Jennifer; Clarridge, Brian

    2012-02-01

    Clinical studies conducted in intensive care units are associated with logistical and ethical challenges. Diseases investigated are precipitous and life-threatening, care is highly technological, and patients are often incapacitated and decision-making is provided by surrogates. These investigations increasingly involve collection of genetic data. The manner in which the exigencies of critical illness impact attitudes regarding genetic data collection is unstudied. Given interest in understanding stakeholder preferences as a foundation for the ethical conduct of research, filling this knowledge gap is timely. The conduct of opinion research in the critical care arena is novel. This brief report describes the development of parallel patient/surrogate decision-maker quantitative survey instruments for use in this environment. Future research employing this instrument or a variant of it with diverse populations promises to inform research practices in critical illness gene variation research.

  3. Criticality considerations for 233U fuels in an HTGR fuel refabrication facility

    International Nuclear Information System (INIS)

    McNeany, S.R.; Jenkins, J.D.

    1978-01-01

    Eleven 233 U solution critical assemblies spanning an H/ 233 U ratio range of 40 to 2000 and a bare metal 233 U assembly have been calculated with the ENDF/B-IV and Hansen-Roach cross sections. The results from these calculations are compared with the experimental results and with each other. An increasing disagreement between calculations with ENDF/B and Hansen-Roach data with decreasing H/ 233 U ratio was observed, indicative of large differences in their intermediate energy cross sections. The Hansen-Roach cross sections appeared to give reasonably good agreement with experiments over the whole range; whereas the ENDF/B calculations yielded high values for k/sub eff/ on assemblies of low moderation. It is concluded that serious problems exist in the ENDF/B-IV representation of the 233 U cross sections in the intermediate energy range and that further evaluation of this nuclide is warranted. In addition, it is recommended that an experimental program be undertaken to obtain 233 U criticality data at low H/ 233 U ratios for verification of generalized criticality safety guidelines. Part II of this report presents the results of criticality calculations on specific pieces of equipment required for HTGR fuel refabrication. In particular, fuel particle storage hoppers and resin carbonization furnaces are criticality safe up to 22.9 cm (9.0 in.) in diameter providing water or other hydrogenous moderators are excluded. In addition, no criticality problems arise due to accumulation of particles in the off-gas scrubber reservoirs provided reasonable administrative controls are exercised

  4. Critical Considerations in Becoming Literacy Educators: Pre-Service Teachers Rehearsing Agency and Negotiating Risk

    Science.gov (United States)

    Ticknor, Anne Swenson

    2015-01-01

    This article looks closely at the talk of two pre-service teachers over time to examine how they used language as a way of rehearsing their evolving agency as literacy educators. Drawing on critical sociocultural theory, I use Agency Tracing to highlight how pre-service teachers' agentic actions are not isolated phenomena but ones developed and…

  5. The Phase I/II BNCT Trials at the Brookhaven medical research reactor: Critical considerations

    International Nuclear Information System (INIS)

    Diaz, A.Z.

    2001-01-01

    A phase I/II clinical trial of boronophenylalanine-fructose (BPA-F) mediated boron neutron capture therapy (BNCT) for Glioblastoma Multiforme (GBM) was initiated at Brookhaven National Laboratory (BNL) in 1994. Many critical issues were considered during the design of the first of many sequential dose escalation protocols. These critical issues included patient selection criteria, boron delivery agent, dose limits to the normal brain, dose escalation schemes for both neutron exposure and boron dose, and fractionation. As the clinical protocols progressed and evaluation of the tolerance of the central nervous system (CNS) to BPA-mediated BNCT at the BMRR continued new specifications were adopted. Clinical data reflecting the progression of the protocols will be presented to illustrate the steps taken and the reasons behind their adoption. (author)

  6. Criticality safety considerations in the geologic disposal of spent nuclear fuel assemblies

    International Nuclear Information System (INIS)

    Gore, B.F.; McNair, G.W.; Heaberlin, S.W.

    1980-05-01

    Features of geologic disposal which hamper the demonstration that criticality cannot occur therein include possible changes of shape and form, intrusion of water as a neutron moderator, and selective leaching of spent fuel constituents. If the criticality safety of spent fuel disposal depends on burnup, independent measurements verifying the burnup should be performed prior to disposal. The status of nondestructive analysis method which might provide such verification is discussed. Calculations were performed to assess the potential for increasing the allowed size of a spent fuel disposal canister if potential water intrusion were limited by close-packing the enclosed rods. Several factors were identified which severely limited the potential of this application. The theoretical limit of hexagonal close-packing cannot be achieved due to fuel rod bowing. It is concluded that disposal canisters should be sized on the basis of assumed optimum moderation. Several topics for additional research were identified during this limited study

  7. Critical considerations on the environmental protection. On the technical regulatory guide of air

    Energy Technology Data Exchange (ETDEWEB)

    Rasch, R

    1978-11-01

    The author critically examines the problem of environmental protection maintaining living conditions even with further development of technology. He deals in detail with the success-promising slogans put forth plastics and hydrochloric acid, nuclear energy, as well as keeping the air clean, sulfur dioxide as main topic from the viewpoint of environmental protection. Furthermore, the technical regulatory guides in maintaining clean air and flue gas purification are treated.

  8. Worker’s Health: Considerations Based on a Criticism of Political Economy

    OpenAIRE

    Ricardo Lara

    2011-01-01

    The purpose of this article is to analyze worker health, based on a criticism of political economy. It seeks to understand the causes of illnesses and accidents among workers, and to highlight elements to consider the struggles of the working class in the realm of health, principally concerning public policies and union practices. It infers that under contemporary labor relations, workers get ill and have accidents due to the intensified pace of production, whether in activities on the factor...

  9. Endoscopic endonasal anatomy of superior orbital fissure and orbital apex regions: critical considerations for clinical applications.

    Science.gov (United States)

    Dallan, Iacopo; Castelnuovo, Paolo; de Notaris, Matteo; Sellari-Franceschini, Stefano; Lenzi, Riccardo; Turri-Zanoni, Mario; Battaglia, Paolo; Prats-Galino, Alberto

    2013-05-01

    The superior orbital fissure is a critical three-dimensional space connecting the middle cranial fossa and the orbit. From an endoscopic viewpoint, only the medial aspect has a clinical significance. It presents a critical relationship with the lateral sellar compartment, the pterygopalatine fossa and the middle cranial fossa. The connective tissue layers and neural and vascular structures of this region are described. The role of Muller's muscle is confirmed, and the utility of the maxillary and optic strut is outlined. Muller's muscle extends for the whole length of the inferior orbital fissure, passes over the maxillary strut and enters the superior orbital fissure, representing a critical surgical landmark. Dividing the tendon between the medial and inferior rectus muscle allows the identification of the main trunk of the oculomotor nerve, and a little laterally, it is usually possible to visualize the first part of the ophthalmic artery. Based on a better knowledge of anatomy, we trust that this area could be readily addressed in clinical situations requiring an extended approach in proximity of the orbital apex.

  10. EFSA CEF Panel (EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids), 2013. Scientific Opinion on Flavouring Group Evaluation 216, Revision 1 (FGE.216Rev1). Consideration of genotoxic potential for α,β-unsaturated 2-Phenyl -2-Alkenals from Subgroup 3.3 of FGE.19

    DEFF Research Database (Denmark)

    Beltoft, Vibe Meister; Binderup, Mona-Lise; Lund, Pia

    The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate the genotoxic potential of five flavouring substances from subgroup 3.3 of FGE.19. In the Flavouring Group Evaluation 216 (FGE.216) additional genotoxicity...... of animals treated with 2-phenylcrotonaldehyde. Moreover, since the substance was genotoxic only without metabolic activation, it appears necessary to prove the absence of genotoxic effect locally in the gastro intestinal system using the Comet assay....

  11. Augmented Renal Clearance in Critical Illness: An Important Consideration in Drug Dosing

    Directory of Open Access Journals (Sweden)

    Sherif Hanafy Mahmoud

    2017-09-01

    Full Text Available Augmented renal clearance (ARC is a manifestation of enhanced renal function seen in critically ill patients. The use of regular unadjusted doses of renally eliminated drugs in patients with ARC might lead to therapy failure. The purpose of this scoping review was to provide and up-to-date summary of the available evidence pertaining to the phenomenon of ARC. A literature search of databases of available evidence in humans, with no language restriction, was conducted. Databases searched were MEDLINE (1946 to April 2017, EMBASE (1974 to April 2017 and the Cochrane Library (1999 to April 2017. A total of 57 records were included in the present review: 39 observational studies (25 prospective, 14 retrospective, 6 case reports/series and 12 conference abstracts. ARC has been reported to range from 14–80%. ARC is currently defined as an increased creatinine clearance of greater than 130 mL/min/1.73 m2 best measured by 8–24 h urine collection. Patients exhibiting ARC tend to be younger (<50 years old, of male gender, had a recent history of trauma, and had lower critical illness severity scores. Numerous studies have reported antimicrobials treatment failures when using standard dosing regimens in patients with ARC. In conclusion, ARC is an important phenomenon that might have significant impact on outcome in critically ill patients. Identifying patients at risk, using higher doses of renally eliminated drugs or use of non-renally eliminated alternatives might need to be considered in ICU patients with ARC. More research is needed to solidify dosing recommendations of various drugs in patients with ARC.

  12. Worker’s Health: Considerations Based on a Criticism of Political Economy

    Directory of Open Access Journals (Sweden)

    Ricardo Lara

    2011-05-01

    Full Text Available The purpose of this article is to analyze worker health, based on a criticism of political economy. It seeks to understand the causes of illnesses and accidents among workers, and to highlight elements to consider the struggles of the working class in the realm of health, principally concerning public policies and union practices. It infers that under contemporary labor relations, workers get ill and have accidents due to the intensified pace of production, whether in activities on the factory floor or in scientific management of labor.

  13. Consideration on the partial moderation in criticality safety analysis of LWR fresh fuel storage

    International Nuclear Information System (INIS)

    Tanaka, S.; Tanimoto, R.; Suzuki, K.; Ishitobi, M.

    1987-01-01

    In criticality safety analyses of fuel fabrication facilities, neutron effective multiplication factor (k eff ) of a storage vault has been calculated assuming ''partial moderation'' in whole space (hereafter reffered to as unlimited partial moderation). Where the enrichment of fuels to be stored is about 3.5 % or less, calculated k eff is usually low enough to show subcriticality even in unlimited partial moderation. However, it is scheduled to elevate LWR fuels enrichment for economical higher burnup and the unlimited partial moderation would require to introduce neutron absorbers to maintain subcriticality. It is clear that this causes economical disadvantages, and hence we reconsidered this assumption to avoid such a condition. Reconsideration of the unlimited partial moderation was carried out in following steps. (1) Water quantity to be assumed in atmosphere to obtain criticality was revealed too much to realize. (2) Typical realistic water quantity in atmosphere was estimated to apply as an alternative assumption. (3) A fresh fuel assembly storage was chosen as a model array and calculations with lattice code WIMS-D 1 and Monte Calro code KENO-IV 2 were performed to compare new alternative assumption with the unlimited one. As results of the above calculations, maximum k eff of the array under the new assumption was remarkably reduced to the value less than 0.95 though the maximum k eff under the unlimited one was higher than 1.0. (author)

  14. Ethical considerations: care of the critically ill and injured during pandemics and disasters: CHEST consensus statement.

    Science.gov (United States)

    Biddison, Lee Daugherty; Berkowitz, Kenneth A; Courtney, Brooke; De Jong, Col Marla J; Devereaux, Asha V; Kissoon, Niranjan; Roxland, Beth E; Sprung, Charles L; Dichter, Jeffrey R; Christian, Michael D; Powell, Tia

    2014-10-01

    Mass critical care entails time-sensitive decisions and changes in the standard of care that it is possible to deliver. These circumstances increase provider uncertainty as well as patients' vulnerability and may, therefore, jeopardize disciplined, ethical decision-making. Planning for pandemics and disasters should incorporate ethics guidance to support providers who may otherwise make ad hoc patient care decisions that overstep ethical boundaries. This article provides consensus-developed suggestions about ethical challenges in caring for the critically ill or injured during pandemics or disasters. The suggestions in this article are important for all of those involved in any pandemic or disaster with multiple critically ill or injured patients, including front-line clinicians, hospital administrators, and public health or government officials. We adapted the American College of Chest Physicians (CHEST) Guidelines Oversight Committee's methodology to develop suggestions. Twenty-four key questions were developed, and literature searches were conducted to identify evidence for suggestions. The detailed literature reviews produced 144 articles. Based on their expertise within this domain, panel members also supplemented the literature search with governmental publications, interdisciplinary workgroup consensus documents, and other information not retrieved through PubMed. The literature in this field is not suitable to support evidence-based recommendations. Therefore, the panel developed expert opinion-based suggestions using a modified Delphi process. We report the suggestions that focus on five essential domains: triage and allocation, ethical concerns of patients and families, ethical responsibilities to providers, conduct of research, and international concerns. Ethics issues permeate virtually all aspects of pandemic and disaster response. We have addressed some of the most pressing issues, focusing on five essential domains: triage and allocation, ethical

  15. A study of fish and shellfish consumers near Sellafield: assessment of the critical groups including consideration of children

    International Nuclear Information System (INIS)

    Leonard, D.R.P.; Hunt, G.J.

    1985-01-01

    A survey of people's consumption rates in 1981 and 1982, of fish and shellfish caught near the British Nuclear Fuels plc (BNFL) Sellafield site is described. Particular emphasis has been given to mollusc eaters and consumption rates of children because of the potentially higher radiation doses they may receive. Appropriate critical groups have been selected for dose assessment purposes using principles recommended by the International Commission on Radiological Protection (ICRP). Methods for consideration of children in critical groups are suggested and a comparison of these methods using the present data shows similar results. Combination of seafood consumption pathways is also considered, and it is shown that a simple additive approach is not excessively conservative. (author)

  16. Critical considerations about the use of poverty measures in the study of cognitive development.

    Science.gov (United States)

    Lipina, Sebastián J

    2017-06-01

    Developmental psychology and developmental cognitive neuroscience generated evidence at different levels of analysis about the influences of poverty on neurocognitive development (i.e., molecular, neural activation, cognition, behaviour). In addition, different individual and environmental factors were identified as mediators of such influences. Such a complexity is also illustrated through the many poverty conceptual and operational definitions generated by social, human and health sciences. However, to establish the causal relationships between the different factors of poverty and neurocognitive outcomes is still an issue under construction. Most studies of this area apply classic unidimensional poverty indicators such as income and maternal education. Nonetheless, this approach does not take into adequate consideration the variability of neurocognitive outcomes depending on the type of poverty measures, and the dynamic nature of changes during development. This creates a virtual underestimation of the complexity imposed by the involved mediating mechanisms. The scientific and policy implications of this underestimation include the risk of not adequately addressing children rights and developmental opportunities. This article proposes to explore such scenario, which is necessary for the reconsideration of the criteria used to analyse the influences of poverty on child development in general and neurocognitive development in particular. © 2016 International Union of Psychological Science.

  17. Bone scanning as a routine examination of patients with mammary carcinoma; a critical consideration. [Preoperative scanning

    Energy Technology Data Exchange (ETDEWEB)

    Heslinga, J M; Pauwels, E K.J.; Zwaveling, A [Rijksuniversiteit Leiden (Netherlands). Academisch Ziekenhuis

    1982-06-05

    The usefulness of bone scanning as a routine examination was evaluated in 136 female patients with mammary carcinoma of whom 81 were staged as Columbia A and 55 as Columbia B/C. The preoperative bone scanning was positive in only 4 patients (2.9%). Consequently, bone scanning is no longer performed in the authors clinic for the preoperative detection of skeletal metastases. Bone scanning as a routine examination at 6-month intervals does not appear to be useful for the first 4 years of the follow-up, either. Most of the patients with a positive bone scan displayed other signs of skeletal metastases at the same time, such as ostealgia and a raised serum alkaline phosphatase level. Further increase of the frequency of bone scanning during the follow-up period would increase the costs considerably, almost prohibitively, even apart from the question whether such a measure might indeed significantly influence the patient's prognosis. The authors conclude that bone scanning should only be performed on the basis of the anamnesis, physical and laboratory findings, both prior to operation and during the follow-up period.

  18. Bone scanning as a routine examination of patients with mammary carcinoma; a critical consideration

    International Nuclear Information System (INIS)

    Heslinga, J.M.; Pauwels, E.K.J.; Zwaveling, A.

    1982-01-01

    The usefulness of bone scanning as a routine examination was evaluated in 136 female patients with mammary carcinoma of whom 81 were staged as Columbia A and 55 as Columbia B/C. The preoperative bone scanning was positive in only 4 patients (2.9%). Consequently, bone scanning is no longer performed in the authors clinic for the preoperative detection of skeletal metastases. Bone scanning as a routine examination at 6-month intervals does not appear to be useful for the first 4 years of the follow-up, either. Most of the patients with a positive bone scan displayed other signs of skeletal metastases at the same time, such as ostealgia and a raised serum alkaline phosphatase level. Further increase of the frequency of bone scanning during the follow-up period would increase the costs considerably, almost prohibitively, even apart from the question whether such a measure might indeed significantly influence the patient's prognosis. The authors conclude that bone scanning should only be performed on the basis of the anamnesis, physical and laboratory findings, both prior to operation and during the follow-up period. (Auth.)

  19. Patient considerations in the management of type 2 diabetes – critical appraisal of dapagliflozin

    Directory of Open Access Journals (Sweden)

    Salvo MC

    2014-04-01

    Full Text Available Marissa C Salvo,1 Amie D Brooks,2 Stacey M Thacker3 1Department of Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, CT, 2Department of Pharmacy Practice, St Louis College of Pharmacy, St Louis, MO, 3Department of Pharmacy Practice, Southern Illinois University Edwardsville, Edwardsville, IL, USA Abstract: Type 2 diabetes affects more than 350 million people worldwide, and its prevalence is increasing. Many patients with diabetes do not achieve and/or maintain glycemic targets, despite therapy implementation and escalation. Multiple therapeutic classes of agents are available for the treatment of type 2 diabetes, and the armamentarium has expanded significantly in the past decade. Selective sodium glucose co-transporter 2 inhibitors, including dapagliflozin, represent the latest development in pharmacologic treatment options for type 2 diabetes. This class has a unique mechanism of action, working by increasing glucose excretion in the urine. The insulin-independent mechanism results in decreased serum glucose, without hypoglycemia or weight gain. Dapagliflozin is a once-daily oral therapy. Expanding therapy options for a complex patient population is critical, and dapagliflozin has a distinct niche that can be a viable option for select patients with diabetes. Keywords: SGLT2 inhibitor, selective sodium glucose co-transporter 2 inhibitors, pharmacological treatment

  20. Criticality considerations for salt-cake disolution in DOE waste tanks

    International Nuclear Information System (INIS)

    Trumble, E.F.; Niemer, K.A.

    1995-01-01

    A large amount of high-level waste is being stored in the form of salt cake at the Savannah River site (SRS) in large (1.3 x 106 gal) underground tanks awaiting startup of the Defense Waste Processing Facility (DWPF). This salt cake will be dissolved with water, and the solution will be fed to DWPF for immobilization in borosilicate glass. Some of the waste that was transferred to the tanks contained enriched uranium and plutonium from chemical reprocessing streams. As water is added to these tanks to dissolve the salt cake, the insoluble portion of this fissile material will be left behind in the tank as the salt solution is pumped out. Because the salt acts as a diluent to the fissile material, the process of repeated water addition, salt dissolution, and salt solution removal will act as a concentrating mechanism for the undissolved fissile material that will remain in the tank. It is estimated that tank 41 H at SRS contains 20 to 120 kg of enriched uranium, varying from 10 to 70% 235 U, distributed nonuniformly throughout the tank. This paper discusses the criticality concerns associated with the dissolution of salt cake in this tank. These concerns are also applicable to other salt cake waste tanks that contain significant quantities of enriched uranium and/or plutonium

  1. Human biological monitoring of occupational genotoxic exposures

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Sorsa, M

    1993-01-01

    Human biological monitoring is a valuable tool for exposure assessment in groups of persons occupationally exposed to genotoxic agents. If the monitoring activity covers genetic material the term genetic monitoring is used. The methods used for genetic monitoring are either substance specific, e......) occupational exposure limit value of styrene in ambient air. The consideration of ethical issues in human genetic monitoring is an important but often overlooked aspect. This includes the scientific and preventional relevance of performing a test on individuals, pre- and post study information of donors...

  2. Quantitative genotoxicity assays for analysis of medicinal plants: A systematic review.

    Science.gov (United States)

    Sponchiado, Graziela; Adam, Mônica Lucia; Silva, Caroline Dadalt; Soley, Bruna Silva; de Mello-Sampayo, Cristina; Cabrini, Daniela Almeida; Correr, Cassyano Januário; Otuki, Michel Fleith

    2016-02-03

    Medicinal plants are known to contain numerous biologically active compounds, and although they have proven pharmacological properties, they can cause harm, including DNA damage. Review the literature to evaluate the genotoxicity risk of medicinal plants, explore the genotoxicity assays most used and compare these to the current legal requirements. A quantitative systematic review of the literature, using the keywords "medicinal plants", "genotoxicity" and "mutagenicity", was undertakenQ to identify the types of assays most used to assess genotoxicity, and to evaluate the genotoxicity potential of medicinal plant extracts. The database searches retrieved 2289 records, 458 of which met the inclusion criteria. Evaluation of the selected articles showed a total of 24 different assays used for an assessment of medicinal plant extract genotoxicity. More than a quarter of those studies (28.4%) reported positive results for genotoxicity. This review demonstrates that a range of genotoxicity assay methods are used to evaluate the genotoxicity potential of medicinal plant extracts. The most used methods are those recommended by regulatory agencies. However, based on the current findings, in order to conduct a thorough study concerning the possible genotoxic effects of a medicinal plant, we indicate that it is important always to include bacterial and mammalian tests, with at least one in vivo assay. Also, these tests should be capable of detecting outcomes that include mutation induction, clastogenic and aneugenic effects, and structural chromosome abnormalities. In addition, the considerable rate of positive results detected in this analysis further supports the relevance of assessing the genotoxicity potential of medicinal plants. Copyright © 2016. Published by Elsevier Ireland Ltd.

  3. Nurses' perceptions of critical issues requiring consideration in the development of guidelines for professional registered nurse staffing for perinatal units.

    Science.gov (United States)

    Simpson, Kathleen Rice; Lyndon, Audrey; Wilson, Jane; Ruhl, Catherine

    2012-01-01

    To solicit input from registered nurse members of the Association of Women's Health, Obstetric and Neonatal Nurses (AWHONN) on critical considerations for review and revision of existing nurse staffing guidelines. Thematic analysis of responses to a cross-sectional on-line survey question: "Please give the staffing task force your input on what they should consider in the development of recommendations for staffing of perinatal units." Members of AWHONN (N = 884). Descriptions of staffing concerns that should be considered when evaluating and revising existing perinatal nurse staffing guidelines. Consistent themes identified included the need for revision of nurse staffing guidelines due to requirements for safe care, increases in patient acuity and complexity, invisibility of the fetus and newborn as separate and distinct patients, difficulties in providing comprehensive care during labor and for mother-baby couplets under current conditions, challenges in staffing small volume units, and the negative effect of inadequate staffing on nurse satisfaction and retention. Participants overwhelmingly indicated current nurse staffing guidelines were inadequate to meet the needs of contemporary perinatal clinical practice and required revision based on significant changes that had occurred since 1983 when the original staffing guidelines were published. © 2012 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

  4. Post-marketing access to orphan drugs: a critical analysis of health technology assessment and reimbursement decision-making considerations

    Directory of Open Access Journals (Sweden)

    Iskrov G

    2014-01-01

    Full Text Available Georgi Iskrov, Rumen Stefanov Department of Social Medicine and Public Health, Medical University of Plovdiv, Plovdiv, Bulgaria Abstract: This study aims to explore the current rationale of post-marketing access to orphan drugs. As access to orphan medicinal products depends on assessment and appraisal by health authorities, this article is focused on health technology assessment (HTA and reimbursement decision-making considerations for orphan drugs. A critical analysis may identify important factors that could predetermine the combined outcomes of these two processes. Following this objective, an analytical framework was developed, comprising three overlaying issues: to outline what is currently done and what needs to be done in the field of HTA of orphan drugs, to synthesize important variables relevant to the reimbursement decision-making about orphan drugs, and to unveil relationships between theory and practice. Methods for economic evaluation, cost-effectiveness threshold, budget impact, uncertainty of evidence, criteria in reimbursement decision-making, and HTA research agenda are all explored and discussed from an orphan drug perspective. Reimbursement decision-making for orphan drugs is a debate of policy priorities, health system specifics, and societal attitudes. Health authorities need to pursue a multidisciplinary analysis on a range of criteria, ensuring an explicit understanding of the trade-offs for decisions related to eligibility for reimbursement. The only reasonable way to accept a higher valuation of orphan drug benefits is if these are demonstrated empirically. Rarity means that the quality of orphan drug evidence is not the same as for conventional therapies. Closing this gap is another crucial point for the timely access to these products. The generation of evidence goes far beyond pre-market authorization trials and requires transnational cooperation and coordination. Early constructive dialogue among orphan drug

  5. Furan: A critical heat induced dietary contaminant

    DEFF Research Database (Denmark)

    Mariotti, María S.; Granby, Kit; Rozowski, Jaime

    2013-01-01

    The presence of furan in a broad range of heat processed foods (0-6000 μg kg-1) has received considerable attention due to the fact that this heat induced contaminant is considered as a "possible carcinogenic compound to humans". Since a genotoxic mode of action could be associated with furan...... of some critical factors such as heating conditions, pH and matrix microstructure are discussed in order to propose some potential methodologies for furan mitigation in a wide range of heated foods. © 2013 The Royal Society of Chemistry....

  6. Consideration of Nuclear Criticality When Directly Disposing Highly Enriched Spent Nuclear Fuel in Unsaturated Tuff - II: Geochemical Constraints

    International Nuclear Information System (INIS)

    Rechard, Rob P.; Sanchez, Lawrence C.; Trellue, Holly R.

    2003-01-01

    This article presents several reasonable cases in which four mechanisms - dissolution, physical mixing, adsorption, and precipitation (either chemical change or evaporation) - might concentrate fissile material in and around a disposal container for radioactive waste at the proposed repository at Yucca Mountain, Nevada. The possible masses, concentrations, and volume are then compared to criticality limits. The cases examined evaluate the geologic barrier role in preventing criticality since engineered options for preventing criticality (e.g., boron or gadolinium neutron absorber in the disposal container) are not considered. The solid concentrations able to form in the natural environment are insufficient for criticality to occur because (a) solutions of 235 U and 239 Pu are clearly not critical; (b) physical mixing of fissile material with the entire potential iron oxide (as goethite - FeOOH) in a waste package is not critical; (c) the adsorption of 239 Pu on consolidated iron oxide in a waste package is not critical; (d) the adsorption of 235 U on consolidated iron oxide in a waste package is not critical when accounting for reduced adsorption because of carbonates at high pH; (e) the filtration of iron oxide colloids, containing fissile material, by the thin invert material is not critical; (f) insufficient retention through precipitation of 235 U or 239 Pu occurs in the invert; (g) adsorption of 235 U and 239 Pu on devitrified or clinoptolite-rich tuff below the repository is not critical; (h) the average precipitation/adsorption of 235 U as uranyl silicates in the tuff is not critical by analogy with calcite deposition in lithophysae at Yucca Mountain; and (i) precipitation/adsorption (caused by cyclic drying) as uranyl silicates on fracture surfaces of the tuff is not critical by analogy with the oxidation of UO 2 , migration of U VI , and precipitation in fractures at the Nopal I ore deposit in Mexico

  7. Assessing noise from wind farm developments in Ireland: A consideration of critical wind speeds and turbine choice

    International Nuclear Information System (INIS)

    King, E.A.; Pilla, F.; Mahon, J.

    2012-01-01

    Wind farms are becoming increasingly popular in Ireland in an effort to increase the production of green energy within the state. As with any infrastructural development, wind farms must consider potential environmental impacts prior to construction. One particular issue that must be examined is the emission of noise from the development. In Ireland wind farm developments must adhere to planning conditions that usually outline permissible noise levels for both the construction and operational phases of the development. The critical wind speed is often cited as the wind speed at which these limits apply. This paper examines how the critical wind speed is determined and investigates its relationship with background noise levels and turbine choice. The study consisted of ten one-week monitoring periods during which meteorological conditions and background noise levels were simultaneously recorded. It was found that the critical wind speed is non-transferable, i.e. it depends on both the turbine choice and background noise environment and is specific to that particular turbine/site combination. Furthermore the critical wind speed during the night-time is often different to the overall critical wind speed suggesting that future noise studies should consider a range of critical wind speeds, particularly for night-time noise assessments. - Highlights: ► This paper considers the use of the critical wind speed when assessing noise impacts from wind farms. ► It was found that the critical wind speed could vary depending on the time of the day. ► The critical wind speed was found to be a non-transferable value. ► Noise assessments for wind farms should be developed over a range of critical wind speeds.

  8. Genotoxicity test of irradiated foods

    International Nuclear Information System (INIS)

    Tanaka, Noriho

    2004-01-01

    Safety tests of radiation irradiated foods started as early as from 1967 in Japan and genotoxicity tests in the Hatano Res. Inst., from 1977. The latter is unique in the world and is reviewed in this paper. Tests included those for the initial injury of DNA, mutagenicity, chromosomal aberration and transformation with use of bacteria, cultured mammalian cells and animals (for chromosomal aberration, micronucleus formation and dominant lethality). Foods tested hitherto were onion, rice, wheat and flour, Vienna sausage, fish sausage (kamaboko), mandarian orange, potato, black pepper and red capsicum, of which extract or powder was subjected to the test. Irradiation doses and its purposes were 0.15-6 kGy γ-ray ( 60 Co) or electron beam by the accelerator (only for the orange), and suppression of germination, pesticide action or sterilization, respectively. Genotoxicity of all foods under tested conditions is shown negative. (N.I.)

  9. HISTORICAL-CRITICAL PEDAGOGY AND SEXUALITY IN SCHOOL EDUCATION: CONSIDERATIONS FROM THE ANALYSIS OF SEXUALITY AS A CROSS-CURRICULAR THEME IN THE NATIONAL CURRICULUM PARAMETERS

    Directory of Open Access Journals (Sweden)

    Márcio Magalhães da Silva

    2015-06-01

    Full Text Available This article examines how the theme “sexual orientation” was inserted in the Brazilian official curriculum from some assumptions of the historical-critical pedagogy, such as the definition of classical knowledge and the role that this pedagogical theory attaches to school education. Thus we question the relevance of the theme for individual development and present some considerations on how it could be taught in schools from the perspective of overcoming the capitalist society.

  10. Selecting an Architecture for a Safety-Critical Distributed Computer System with Power, Weight and Cost Considerations

    Science.gov (United States)

    Torres-Pomales, Wilfredo

    2014-01-01

    This report presents an example of the application of multi-criteria decision analysis to the selection of an architecture for a safety-critical distributed computer system. The design problem includes constraints on minimum system availability and integrity, and the decision is based on the optimal balance of power, weight and cost. The analysis process includes the generation of alternative architectures, evaluation of individual decision criteria, and the selection of an alternative based on overall value. In this example presented here, iterative application of the quantitative evaluation process made it possible to deliberately generate an alternative architecture that is superior to all others regardless of the relative importance of cost.

  11. Consciousness as a phenomenon in the operational architectonics of brain organization: Criticality and self-organization considerations

    International Nuclear Information System (INIS)

    Fingelkurts, Andrew A.; Fingelkurts, Alexander A.; Neves, Carlos F.H.

    2013-01-01

    In this paper we aim to show that phenomenal consciousness is realized by a particular level of brain operational organization and that understanding human consciousness requires a description of the laws of the immediately underlying neural collective phenomena, the nested hierarchy of electromagnetic fields of brain activity – operational architectonics. We argue that the subjective mental reality and the objective neurobiological reality, although seemingly worlds apart, are intimately connected along a unified metastable continuum and are both guided by the universal laws of the physical world such as criticality, self-organization and emergence

  12. Feasibility and incentives for the consideration of spent fuel operating histories in the criticality analysis of spent fuel shipping casks

    International Nuclear Information System (INIS)

    Sanders, T.L.; Westfall, R.M.; Jones, R.H.

    1987-08-01

    Analyses have been completed that indicate the consideration of spent fuel histories (''burnup credit'') in the design of spent fuel shipping casks is a justifiable concept that would result in cost savings and public risk benefits in the transport of spent nuclear fuel. Since cask capacities could be increased over those of casks without burnup credit, the number of shipments necessary to transport a given amount of fuel could be reduced. Reducing the number of shipments would increase safety benefits by reducing public and occupational exposure to both radiological and nonradiological risks associated with the transport of spent fuel. Economic benefits would include lower in-transit shipping, reduced transportation fleet capital costs, and reduced numbers of cask handling operations at both shipping and receiving facilities. 44 refs., 66 figs., 28 tabs

  13. Commentary: critical questions, misconceptions and a road map for improving the use of the lymphocyte cytokinesis-block micronucleus assay for in vivo biomonitoring of human exposure to genotoxic chemicals-a HUMN project perspective.

    Science.gov (United States)

    Kirsch-Volders, Micheline; Bonassi, Stefano; Knasmueller, Siegfried; Holland, Nina; Bolognesi, Claudia; Fenech, Michael F

    2014-01-01

    The lymphocyte cytokinesis-block micronucleus (CBMN) assay has been applied in hundreds of in vivo biomonitoring studies of humans exposed to genotoxic chemicals because it allows the measurement of both structural and numerical chromosome aberrations. The CBMN cytome assay version which, apart from measuring micronuclei (MN) already present in cells in vivo or expressed ex vivo, also includes measurement of nucleoplasmic bridges (NPB), nuclear buds (NBUD), necrosis and apoptosis, is also increasingly being used in such studies. Because of the numerous published studies there is now a need to re-evaluate the use of MN and other biomarkers within the lymphocyte CBMN cytome assay as quantitative indicators of exposure to chemical genotoxins and the genetic hazard this may cause. This review has identified some important misconceptions as well as knowledge gaps that need to be addressed to make further progress in the proper application of this promising technique and enable its full potential to be realised. The HUMN project consortium recommends a three pronged approach to further improve the knowledge base and application of the lymphocyte CBMN cytome assay to measure DNA damage in humans exposed to chemical genotoxins: (i) a series of systematic reviews, one for each class of chemical genotoxins, of studies which have investigated the association of in vivo exposure in humans with MN, NPB and NBUD induction in lymphocytes; (ii) a comprehensive analysis of the literature to obtain new insights on the potential mechanisms by which different classes of chemicals may induce MN, NPB and NBUD in vitro and in vivo and (iii) investigation of the potential advantages of using the lymphocyte CBMN cytome assay in conjunction with other promising complementary DNA damage diagnostics to obtain an even more complete assessment of the DNA damage profile induced by in vivo exposure to chemical genotoxins in humans. Copyright © 2014 The Authors. Published by Elsevier B.V. All

  14. Toward a Genotoxic Protection Factor

    International Nuclear Information System (INIS)

    Cesarini, J.P.; Demanneville, S.

    2000-01-01

    P53, a molecule normally expressed before mitosis, is considered as the 'guardian of the genome'. In the skin its level is normally very low (<3% of cells), detected by immunohistochemical methods. At least 50% of the keratinocytes express p53 protein, 24 h following a significant UV irradiation (2 SED). It is expected using sunscreens to reduce the expression of p53 in parallel with their ability to reduce the actinic erythema, the endpoint adopted to evaluate the Sun Protection Factor (SPF) of sunscreens. P53 detection on biopsies performed on the buttocks of human volunteers was used to evaluate the genotoxic protecting factor (GPF) of several sunscreens with either high UVB filtration or high UVA filtration, characterised by various SPF (COLIPA) from 10 to 40. The p53 count in parallel with sunburn cell count were the parameters studied. In general, the GPF of the sunscreens was found below the proprietary SPF. If a genotoxic effect is shown in an increased p53 expression, this effect is still observed at a dose lower than the dose inducing the faintest actinic erythema. (author)

  15. Toward a Genotoxic Protection Factor

    Energy Technology Data Exchange (ETDEWEB)

    Cesarini, J.P.; Demanneville, S

    2000-07-01

    P53, a molecule normally expressed before mitosis, is considered as the 'guardian of the genome'. In the skin its level is normally very low (<3% of cells), detected by immunohistochemical methods. At least 50% of the keratinocytes express p53 protein, 24 h following a significant UV irradiation (2 SED). It is expected using sunscreens to reduce the expression of p53 in parallel with their ability to reduce the actinic erythema, the endpoint adopted to evaluate the Sun Protection Factor (SPF) of sunscreens. P53 detection on biopsies performed on the buttocks of human volunteers was used to evaluate the genotoxic protecting factor (GPF) of several sunscreens with either high UVB filtration or high UVA filtration, characterised by various SPF (COLIPA) from 10 to 40. The p53 count in parallel with sunburn cell count were the parameters studied. In general, the GPF of the sunscreens was found below the proprietary SPF. If a genotoxic effect is shown in an increased p53 expression, this effect is still observed at a dose lower than the dose inducing the faintest actinic erythema. (author)

  16. EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Ai ds (CEF); Scientific Opinion on Flavouring Group Evaluation 208 (FGE.208): Consideration of genotoxicity data on representatives for 10 alicyclic aldehydes with the α , β - unsaturation in ring / side - chain

    DEFF Research Database (Denmark)

    Beltoft, Vibe Meister; Binderup, Mona-Lise; Lund, Pia

    The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate the genotoxic potential of one flavouring substance from subgroup 2.2 of FGE.19 in the Flavouring Group Evaluation 208. The Flavour Industry has provided a...

  17. EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 226 (FGE.226): Consideration of genotoxicity data on one α,β-unsaturated aldehyde from chemical subgroup 1.1.1(b) of FGE.19 by EFSA

    DEFF Research Database (Denmark)

    Larsen, John Christian; Nørby, Karin Kristiane; Beltoft, Vibe Meister

    The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate the genotoxic potential of one flavouring substance from subgroup 1.1.1(b) of FGE.19 in the Flavouring Group Evaluation 226. The Flavour Industry has provi...

  18. EFSA CEF Panel (EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids), 2014. Scientific Opinion on Flavouring Group Evaluation 213, Revision 1 (FGE.213Rev1): Consideration of genotoxic potential for α , β -Unsaturated Alicyclic ketones and precursors from chemical subgroup

    DEFF Research Database (Denmark)

    Beltoft, Vibe Meister; Binderup, Mona-Lise; Lund, Pia

    The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate the genotoxic potential of 26 flavouring substances from subgroup 2.7 of FGE.19 in the Flavouring Group Evaluation 213. In the first version of FGE.213 the...

  19. EFSA CEF Panel (EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids), 2013. Scientific Opinion on Flavouring Group Evaluation 217, Revision 1 (FGE.217Rev1). Consideration of genotoxic potential for α,β-Unsaturated ketones and precursors from chemical subgroup 4.1 of FGE

    DEFF Research Database (Denmark)

    Beltoft, Vibe Meister; Binderup, Mona-Lise; Lund, Pia

    The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate the genotoxic potential of 12 flavouring substances from subgroup 4.1 of FGE.19 in the Flavouring Group Evaluation 217 (FGE.217). In FGE.217, 6-methylcouma...

  20. EFSA CEF Panel (EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids), 2015. Scientific Opinion on Flavouring Group Evaluation 213, Revision 2 (FGE.213Rev2): Consideration of genotoxic potential for α,β-unsaturated alicyclic ketones and precursors from chemical subgroup 2

    DEFF Research Database (Denmark)

    Beltoft, Vibe Meister; Nørby, Karin Kristiane

    The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF Panel) of the European Food Safety Authority (EFSA) was requested to evaluate the genotoxic potential of 26 flavouring substances from subgroup 2.7 of FGE.19 in Flavouring Group Evaluation (FGE) 213. In the first v...

  1. EFSA CEF Panel (EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids), 2014. Scientific Opinion on Flavouring Group Evaluation 210, Revision 1 (FGE.210Rev1): Consideration of genotoxic potential for α,β-unsaturated alicyclic ketones and precursors from chemical subgroup 2

    DEFF Research Database (Denmark)

    Beltoft, Vibe Meister; Binderup, Mona-Lise; Lund, Pia

    The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate the genotoxic potential of 13 flavouring substances in Flavouring Group Evaluation 210 (FGE.210) and one additional substance [FL-no: 07.225] in this revis...

  2. Comparison of the in vivo and in vitro genotoxicity of glyphosate isopropylamine salt in three different organisms

    Directory of Open Access Journals (Sweden)

    Carlos Alvarez-Moya

    2014-01-01

    Full Text Available There is considerable controversy with regard to the genotoxicity of glyphosate, with some reports stating that this compound is non-toxic for fish, birds and mammals. In this work, we used the comet assay to examine the genotoxicity of glyphosate isopropylamine (0.7, 7, 70 and 700 µM in human lymphocytes, erythrocytes of Oreochromis niloticus and staminal nuclei of Tradescantia (4430 in vitro and in vivo. Cells, nuclei and fish that had and had not been exposed to 5 mM N-nitrosodiethylamine (NDEA were used as positive and negative controls, respectively. Significant (p 7 µM, whereas in vitro, glyphosphate was genotoxic in human lymphocytes and Tradescantia hairs at > 0.7 µM. These results indicate that glyphosate is genotoxic in the cells and organisms studied at concentrations of 0.7-7 µM.

  3. DNA dosimetry assessment for sunscreen genotoxic photoprotection.

    Directory of Open Access Journals (Sweden)

    André Passaglia Schuch

    Full Text Available Due to the increase of solar ultraviolet radiation (UV incidence over the last few decades, the use of sunscreen has been widely adopted for skin protection. However, considering the high efficiency of sunlight-induced DNA lesions, it is critical to improve upon the current approaches that are used to evaluate protection factors. An alternative approach to evaluate the photoprotection provided by sunscreens against daily UV radiation-induced DNA damage is provided by the systematic use of a DNA dosimeter.The Sun Protection Factor for DNA (DNA-SPF is calculated by using specific DNA repair enzymes, and it is defined as the capacity for inhibiting the generation of cyclobutane pyrimidine dimers (CPD and oxidised DNA bases compared with unprotected control samples. Five different commercial brands of sunscreen were initially evaluated, and further studies extended the analysis to include 17 other products representing various formulations and Sun Protection Factors (SPF. Overall, all of the commercial brands of SPF 30 sunscreens provided sufficient protection against simulated sunlight genotoxicity. In addition, this DNA biosensor was useful for rapidly screening the biological protection properties of the various sunscreen formulations.The application of the DNA dosimeter is demonstrated as an alternative, complementary, and reliable method for the quantification of sunscreen photoprotection at the level of DNA damage.

  4. DNA dosimetry assessment for sunscreen genotoxic photoprotection.

    Science.gov (United States)

    Schuch, André Passaglia; Lago, Juliana Carvalhães; Yagura, Teiti; Menck, Carlos Frederico Martins

    2012-01-01

    Due to the increase of solar ultraviolet radiation (UV) incidence over the last few decades, the use of sunscreen has been widely adopted for skin protection. However, considering the high efficiency of sunlight-induced DNA lesions, it is critical to improve upon the current approaches that are used to evaluate protection factors. An alternative approach to evaluate the photoprotection provided by sunscreens against daily UV radiation-induced DNA damage is provided by the systematic use of a DNA dosimeter. The Sun Protection Factor for DNA (DNA-SPF) is calculated by using specific DNA repair enzymes, and it is defined as the capacity for inhibiting the generation of cyclobutane pyrimidine dimers (CPD) and oxidised DNA bases compared with unprotected control samples. Five different commercial brands of sunscreen were initially evaluated, and further studies extended the analysis to include 17 other products representing various formulations and Sun Protection Factors (SPF). Overall, all of the commercial brands of SPF 30 sunscreens provided sufficient protection against simulated sunlight genotoxicity. In addition, this DNA biosensor was useful for rapidly screening the biological protection properties of the various sunscreen formulations. The application of the DNA dosimeter is demonstrated as an alternative, complementary, and reliable method for the quantification of sunscreen photoprotection at the level of DNA damage.

  5. DNA Dosimetry Assessment for Sunscreen Genotoxic Photoprotection

    Science.gov (United States)

    Schuch, André Passaglia; Lago, Juliana Carvalhães; Yagura, Teiti; Menck, Carlos Frederico Martins

    2012-01-01

    Background Due to the increase of solar ultraviolet radiation (UV) incidence over the last few decades, the use of sunscreen has been widely adopted for skin protection. However, considering the high efficiency of sunlight-induced DNA lesions, it is critical to improve upon the current approaches that are used to evaluate protection factors. An alternative approach to evaluate the photoprotection provided by sunscreens against daily UV radiation-induced DNA damage is provided by the systematic use of a DNA dosimeter. Methodology/Principal Findings The Sun Protection Factor for DNA (DNA-SPF) is calculated by using specific DNA repair enzymes, and it is defined as the capacity for inhibiting the generation of cyclobutane pyrimidine dimers (CPD) and oxidised DNA bases compared with unprotected control samples. Five different commercial brands of sunscreen were initially evaluated, and further studies extended the analysis to include 17 other products representing various formulations and Sun Protection Factors (SPF). Overall, all of the commercial brands of SPF 30 sunscreens provided sufficient protection against simulated sunlight genotoxicity. In addition, this DNA biosensor was useful for rapidly screening the biological protection properties of the various sunscreen formulations. Conclusions/Significance The application of the DNA dosimeter is demonstrated as an alternative, complementary, and reliable method for the quantification of sunscreen photoprotection at the level of DNA damage. PMID:22768281

  6. Decisions to regulate genotoxic substances

    Energy Technology Data Exchange (ETDEWEB)

    Bengtsson, G

    1988-07-01

    Decisions to regulate genotoxic substances involve trade-offs between various incomparable factors such as risks to human health and other environmental risks, public perceptions, costs and uncertainties. Two different approaches towards these trade-offs are discussed. In one approach, all relevant factors are defined and trade-offs are considered using a general and very elaborate analysis. Cost-benefit analysis is an exponent of this approach. An illustration is given for the regulation of transboundary releases of radioactive materials. The other approach considers what is politically feasible for the time being and seeks a decision with much room for later corrections. Incrementalism is a philosophy in this vein. It is illustrated by reference to the regulation of transboundary air pollution. Weaknesses and strengths of the two approaches are discussed. (author)

  7. Decisions to regulate genotoxic substances

    International Nuclear Information System (INIS)

    Bengtsson, G.

    1988-01-01

    Decisions to regulate genotoxic substances involve trade-offs between various incomparable factors such as risks to human health and other environmental risks, public perceptions, costs and uncertainties. Two different approaches towards these trade-offs are discussed. In one approach, all relevant factors are defined and trade-offs are considered using a general and very elaborate analysis. Cost-benefit analysis is an exponent of this approach. An illustration is given for the regulation of transboundary releases of radioactive materials. The other approach considers what is politically feasible for the time being and seeks a decision with much room for later corrections. Incrementalism is a philosophy in this vein. It is illustrated by reference to the regulation of transboundary air pollution. Weaknesses and strengths of the two approaches are discussed. (author)

  8. EFSA Panel on Food Contact Materials , Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 224 (FGE.224): Consideration of genotoxic potential for two α,β - unsaturated thiophenes from subgroup 5.2 of FGE.19 by EFSA

    DEFF Research Database (Denmark)

    Beltoft, Vibe Meister; Binderup, Mona-Lise; Lund, Pia

    The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate the genotoxic potential of two flavouring substances from subgroup 5.2 of FGE.19 in the Flavouring Group Evaluation 224 (FGE.224). The Flavour Industry has...... provided additional genotoxicity studies for one of the two substances in FGE.224, namely 5-methyl-2-thiophenecarbaldehyde [FL-no: 15.004]. The data requested by EFSA for the other substance, 3-acetyl-2,5-dimethylthiophene [FL-no: 15.024] of FGE.224 will be provided subsequently according to the Flavour...... are still pending and no conclusion could be drawn in the present FGE. © European Food Safety Authority, 2013...

  9. EFSA Panel on Food Contact Material, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 222: Consideration of genotoxicity data on representatives for alpha,betaunsaturated furyl derivatives with the α,β-unsaturation in the side chain from subgroup 4.6 of FGE.19 by EFSA

    DEFF Research Database (Denmark)

    Larsen, John Christian; Nørby, Karin Kristiane; Beltoft, Vibe Meister

    additional genotoxicity studies for two representative substances, 3-(2-furyl)acrylaldehyde [FL-no: 13.034] and 4-(2-furyl)but-3-en-2-one [FL-no: 13.044], in FGE.222. Based on these new data the Panel could not rule out a clastogenic and aneugenic potential for the two substances and a in vivo Comet assay...... was requested for both substances, the one including a micronucleus assay....

  10. Genotoxic effects of environmental pollutants genotoxic monitoring and detection of antigenotoxic effects

    International Nuclear Information System (INIS)

    Simic, D.; Knezevic-Vukcevic, J.; Vukovi -Gacic, B.; Mitic, D.; Beric, T.; Nikolic, B.; Stanojevic, J.; Stankovic, S.

    2002-01-01

    The control of genotoxic agents mass release, which can adversely affect the ecosystem stability and human health is of the greatest importance. Therefore, it is necessary to seriously elaborate the strategy of genotoxic monitoring and relevant legislation. Additional approach is the study and dietary use of antigenotoxic plant substances for prevention of mutation-related diseases. (author)

  11. Genotoxic effects of environmental pollutants genotoxic monitoring and detection of antigenotoxic effects

    Energy Technology Data Exchange (ETDEWEB)

    Simic, D; Knezevic-Vukcevic, J; Vukovi -Gacic, B; Mitic, D; Beric, T; Nikolic, B; Stanojevic, J; Stankovic, S [Faculty of Biology, University of Belgrade, Belgrade (Yugoslavia)

    2002-05-01

    The control of genotoxic agents mass release, which can adversely affect the ecosystem stability and human health is of the greatest importance. Therefore, it is necessary to seriously elaborate the strategy of genotoxic monitoring and relevant legislation. Additional approach is the study and dietary use of antigenotoxic plant substances for prevention of mutation-related diseases. (author)

  12. Management of infections in critically ill returning travellers in the intensive care unit—II: clinical syndromes and special considerations in immunocompromised patients

    Directory of Open Access Journals (Sweden)

    Jordi Rello

    2016-07-01

    Full Text Available This position paper is the second ESCMID Consensus Document on this subject and aims to provide intensivists, infectious disease specialists, and emergency physicians with a standardized approach to the management of serious travel-related infections in the intensive care unit (ICU or the emergency department. This document is a cooperative effort between members of two European Society of Clinical Microbiology and Infectious Diseases (ESCMID study groups and was coordinated by Hakan Leblebicioglu and Jordi Rello for ESGITM (ESCMID Study Group for Infections in Travellers and Migrants and ESGCIP (ESCMID Study Group for Infections in Critically Ill Patients, respectively. A relevant expert on the subject of each section prepared the first draft which was then edited and approved by additional members from both ESCMID study groups. This article summarizes considerations regarding clinical syndromes requiring ICU admission in travellers, covering immunocompromised patients.

  13. Critical Consideration on TV Culture

    Institute of Scientific and Technical Information of China (English)

    涂艳

    2015-01-01

    Since TV culture has been the mainstream,TV,as an important cultural media,have spread its influence widely and rapidly so as to alter people’s ideology and life style.The emergency of TV has brought about convenience and happiness and created popularity,but due to its vulgarity,it has inevitably become one of piece of the mainstream culture and a means of social control.

  14. GENOTOXICITY OF TOBACCO SMOKE AND TOBACCO SMOKE CONDENSATE: A REVIEW

    Science.gov (United States)

    Genotoxicity of Tobacco Smoke and Tobacco Smoke Condensate: A ReviewAbstractThis report reviews the literature on the genotoxicity of main-stream tobacco smoke and cigarette smoke condensate (CSC) published since 1985. CSC is genotoxic in nearly all systems in which it h...

  15. Genotoxic evaluation of polymeric nanoparticles

    Directory of Open Access Journals (Sweden)

    Tamara Iglesias Alonso

    2015-06-01

    Full Text Available An important strategy for optimizing the therapeutic efficacy of many conventional drugs is the development of polymeric nanoparticles (NPs, as it may expand their activities, reduce their toxicity, increase their bioactivity and improve biodistribution. The main objective of this study was to evaluate the genotoxicity of 8 different poly (anhydride NPs designed for the oral administration of therapeutic compounds by using the comet assay in combination with the enzyme formamidopypiridine DNA-glycosylase (FPG. Furthermore, the mitogen capacity of the NPs was evaluated by the proliferation assay. All NPs were tested at four concentrations (0, 0.5, 1 and 2 mg/mL in Caco-2 cells after 3 hours of treatment while selected NPs were also tested after 24 h. The comet assay was performed immediately after the treatment and cell proliferation was assessed by counting the treated cells after their incubation at 37 °C for 48h. Cells treated with 1 µM of the photosensitizer Ro 19-8022 plus 5 min of light, as well as cells treated with 100 µM H2O2 were included as positive controls in all the experiments. All NPs studied did not result in any increase in the frequency of strand breaks or alkali-labile sites in Caco-2 cells but they induced a slight concentration-dependent increase in net FPG sensitive sites (oxidized and/or alkylated bases. Furthermore, treated cells did not show changes in levels of proliferation in comparison with the negative control.

  16. Scientific opinion of Flavouring Group Evaluation 205 Revision 1 (FGE.205Rev1): consideration of genotoxicity data on representatives for 13 α,β-unsaturated aliphatic ketones with terminal double bonds and precursors from chemical subgroup 1.2.2 of FGE.19

    DEFF Research Database (Denmark)

    Beltoft, Vibe Meister; Nørby, Karin Kristiane

    The EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF Panel) was requested to consider in the Flavouring Group Evaluation 205 (FGE.205), the additional data on genotoxicity submitted by the Industry on two representative substances, oct-1-en-3-one [FL-no: 07.......081] and pent-1-en-3-one [FL-no: 07.102], from subgroup 1.2.2 of FGE.19. The Panel concluded that both substances were weakly genotoxic in bacteria with pent-1-en-3-one being the most potent (previously available data). In these assays, the representative substances were highly cytotoxic with a steep toxicity...... of the representative substances, pent-1-en-3-one, in an in vivo Comet assay on the first site of contact (e.g. the stomach or duodenum) and on the liver. The Industry has now submitted new data, a combined micronucleus and Comet assay for pent-1-en-3-one, with scoring in the liver and duodenum, and an Ames test...

  17. A novel mechanism of oxidative genotoxicity

    Indian Academy of Sciences (India)

    The genotoxicity of reactive oxygen species (ROS) is well established. The underlying mechanism involves oxidation of DNA by ROS. However, we have recently shown that hydrogen peroxide (H2O2), the major mediator of oxidative stress, can also cause genomic damage indirectly. Thus, H2O2 at pathologically relevant ...

  18. Comparative Physicochemical and Genotoxicity Assessments of ...

    African Journals Online (AJOL)

    ADOWIE PERE

    ABSTRACT: The textile industry has become indispensable in view of its basic and social importance to human life, but its environmental impact has continued to be a subject of concern. ... the economy of many countries. ... Textile and clothing production process ..... Genotoxicity screening of industrial effluents using.

  19. "Aspartame: A review of genotoxicity data".

    Science.gov (United States)

    Kirkland, David; Gatehouse, David

    2015-10-01

    Aspartame is a methyl ester of a dipeptide of aspartic acid and phenylalanine. It is 200× sweeter than sucrose and is approved for use in food products in more than 90 countries around the world. Aspartame has been evaluated for genotoxic effects in microbial, cell culture and animal models, and has been subjected to a number of carcinogenicity studies. The in vitro and in vivo genotoxicity data available on aspartame are considered sufficient for a thorough evaluation. There is no evidence of induction of gene mutations in a series of bacterial mutation tests. There is some evidence of induction of chromosomal damage in vitro, but this may be an indirect consequence of cytotoxicity. The weight of evidence from in vivo bone marrow micronucleus, chromosomal aberration and Comet assays is that aspartame is not genotoxic in somatic cells in vivo. The results of germ cell assays are difficult to evaluate considering limited data available and deviations from standard protocols. The available data therefore support the conclusions of the European Food Safety Authority (EFSA) that aspartame is non-genotoxic. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. E2F1 transcription is induced by genotoxic stress through ATM/ATR activation.

    Science.gov (United States)

    Carcagno, Abel L; Ogara, María F; Sonzogni, Silvina V; Marazita, Mariela C; Sirkin, Pablo F; Ceruti, Julieta M; Cánepa, Eduardo T

    2009-05-01

    E2F1, a member of the E2F family of transcription factors, plays a critical role in controlling both cell cycle progression and apoptotic cell death in response to DNA damage and oncogene activation. Following genotoxic stresses, E2F1 protein is stabilized by phosphorylation and acetylation driven to its accumulation. The aim of the present work was to examine whether the increase in E2F1 protein levels observed after DNA damage is only a reflection of an increase in E2F1 protein stability or is also the consequence of enhanced transcription of the E2F1 gene. The data presented here demonstrates that UV light and other genotoxics induce the transcription of E2F1 gene in an ATM/ATR dependent manner, which results in increasing E2F1 mRNA and protein levels. After genotoxic stress, transcription of cyclin E, an E2F1 target gene, was significantly induced. This induction was the result of two well-differentiated effects, one of them dependent on de novo protein synthesis and the other on the protein stabilization. Our results strongly support a transcriptional effect of DNA damaging agents on E2F1 expression. The results presented herein uncover a new mechanism involving E2F1 in response to genotoxic stress.

  1. Mixture Genotoxicity of 2,4-Dichlorophenoxyacetic Acid, Acrylamide, and Maleic Hydrazide on Human Caco-2 Cells Assessed with Comet Assay

    DEFF Research Database (Denmark)

    Syberg, Kristian; Binderup, Mona-Lise; Cedergreen, Nina

    2015-01-01

    Assessment of genotoxic properties of chemicals is mainly conducted only for single chemicals, without taking mixture genotoxic effects into consideration. The current study assessed mixture effects of the three known genotoxic chemicals, 2,4-dichlorophenoxyacetic acid (2,4-D), acrylamide (AA......), and maleic hydrazide (MH), in an experiment with a fixed ratio design setup. The genotoxic effects were assessed with the single-cell gel electrophoresis assay (comet assay) for both single chemicals and the ternary mixture. The concentration ranges used were 0-1.4, 0-20, and 0-37.7 mM for 2,4-D, AA, and MH......, respectively. Mixture toxicity was tested with a fixed ratio design at a 10:23:77% ratio for 2.4-D:AA:MH. Results indicated that the three chemicals yielded a synergistic mixture effect. It is not clear which mechanisms are responsible for this interaction. A few possible interactions are discussed...

  2. EFSA CEF Panel (EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids), 2015. Scientific Opinion on Flavouring Group Evaluation 208 Revision 1 (FGE.208Rev1): Consideration of genotoxicity data on representatives for 10 alicyclic aldehydes with the a,b-unsaturation in ring / side-chain and precursors from chemical subgroup 2.2 of FGE.19

    DEFF Research Database (Denmark)

    Beltoft, Vibe Meister; Nørby, Karin Kristiane

    genotoxicity studies on p-mentha-1,8-dien-7-al [FL-no: 05.117], the representative substance for FGE.19 subgroup 2.2. This substance was tested in vivo in a combined micronucleus assay in bone marrow and Comet assay in liver and duodenum. It did not induce any increase in micronucleated polychromatic...... erythrocytes of the bone marrow of male rats in the micronucleus test and it did not induce DNA damage in duodenum of the same animals as analysed by the Comet assay. The Comet assay performed in liver shows a positive result and therefore the Panel concluded that p-mentha-1,8-dien-7-al [FL-no: 05...

  3. An evaluation of the genotoxic and cytotoxic effects of the anti-obesity drugs sibutramine and fenproporex.

    Science.gov (United States)

    da Silva, Cristiano José; dos Santos, José Ernesto; Satie Takahashi, Catarina

    2010-03-01

    Anti-obesity medications deserve special considerations at the present time due to an increasing number of overweight and obese people who require these therapeutic alternatives. Obesity is positively associated with several chronic illnesses, including cancer. In this work, we evaluated the possible genotoxic and/or cytotoxic actions of two drugs, sibutramine and fenproporex, in the doses of 10, 20 and 40 mg/kg body weight (bw), administered intraperitoneally in male Swiss mice. The genotoxic effect was analyzed by comet assay and micronucleus test. We found that both drugs increased the frequency of genotoxic damage in Swiss mice, but did not present cytotoxic activities towards the polychromatic erythrocytes of the bone marrow of these animals.

  4. Oxcarbazepine-induced cytotoxicity and genotoxicity in human lymphocyte cultures with or without metabolic activation.

    Science.gov (United States)

    Atlı Şekeroğlu, Zülal; Kefelioğlu, Haluk; Kontaş Yedier, Seval; Şekeroğlu, Vedat; Delmecioğlu, Berrin

    2017-03-01

    There has been considerable debate about the relationship between epilepsy and cancer. Oxcarbazepine (OXC) is used for treating certain types of seizures in patients with epilepsy. There have been no detailed investigations about genotoxicity of OXC and its metabolites. Therefore, the aim of this study is to investigate the cytotoxic and genotoxic effects of OXC and its metabolites on cultured human lymphocytes. The cytotoxicity and genotoxicity of OXC on human peripheral blood lymphocytes were examined in vitro by sister chromatid exchange (SCE), chromosomal aberration (CA) and micronucleus (MN) tests. Cultures were treated with 125, 250 and 500 μg/ml of OXC in the presence (3 h treatment) and absence (24 h and 48 h treatment) of a metabolic activator (S9 mix). Dimethyl sulfoxide (DMSO) was used as a solvent control. OXC showed cytotoxic activities due to significant decreases in mitotic index (MI), proliferation index (PI) and nuclear division index (NDI) in the absence of S9 mix when compared with solvent control. Metabolites of OXC also significantly reduced MI and PI in cultures with S9 mix. OXC significantly increased the CAs, aberrant cells, SCE and MN values in the presence and absence of S9 mix. Our results indicated that both OXC and its metabolites have cytotoxic, cytostatic and genotoxic potential on human peripheral blood lymphocyte cultures under the experimental conditions. Further studies are necessary to elucidate the relationship between cytotoxic, cytostatic and genotoxic effects, and to make a possible risk assessment in patients receiving therapy with this drug.

  5. Ecotoxicity and genotoxicity assessment of cytostatic pharmaceuticals

    Czech Academy of Sciences Publication Activity Database

    Zounková, R.; Odráška, P.; Doležalová, L.; Hilscherová, Klára; Maršálek, Blahoslav; Bláha, Luděk

    2007-01-01

    Roč. 26, č. 10 (2007), s. 2208-2214 ISSN 0730-7268 Grant - others:GA MŠk(CZ) 2B06171; ECODIS(XE) 518043-1 Institutional research plan: CEZ:AV0Z60050516 Source of funding: R - rámcový projekt EK Keywords : cytostatic pharmaceuticals * genotoxicity * antineoplastics Subject RIV: EF - Botanics Impact factor: 2.309, year: 2007

  6. Genoprotective and Genotoxic Effects of Thymoquinone on ...

    African Journals Online (AJOL)

    Comet assays and apoptotic cell studies were performed to evaluate the effect of TQ on the cytotoxicity and genotoxicity-induced by DXR. Results: TQ treatment, alone, (5.0, 10, or 20 µM) increased DNA damage index (DI) in a concentrationdependent manner (0.64 ± 0.09, 0.84 ± 0.07, and 0.93 ± 0.06, respectively).

  7. Cytotoxicity and genotoxicity of biogenic silver nanoparticles

    International Nuclear Information System (INIS)

    Lima, R; Feitosa, L O; Ballottin, D; Tasic, L; Durán, N; Marcato, P D

    2013-01-01

    Biogenic silver nanoparticles with 40.3 ± 3.5 nm size and negative surface charge (− 40 mV) were prepared with Fusarium oxysporum. The cytotoxicity of 3T3 cell and human lymphocyte were studied by a TaliTM image-based cytometer and the genotoxicity through Allium cepa and comet assay. The results of BioAg-w (washed) and BioAg-nw (unwashed) biogenic silver nanoparticles showed cytotoxicity exceeding 50 μg/mL with no significant differences of response in 5 and 10 μg/mL regarding viability. Results of genotoxicity at concentrations 5.0 and 10.0 ug/mL show some response, but at concentrations 0.5 and 1.0 μg/mL the washed and unwashed silver nanoparticles did not present any effect. This in an important result since in tests with different bacteria species and strains, including resistant, MIC (minimal inhibitory concentration) had good answers at concentrations less than 1.9 μg/mL. This work concludes that biogenic silver nanoparticles may be a promising option for antimicrobial use in the range where no cyto or genotoxic effect were observed. Furthermore, human cells were found to have a greater resistance to the toxic effects of silver nanoparticles in comparison with other cells.

  8. METABOLISM, GENOTOXICITY, AND CARCINOGENICITY OF COMFREY

    Science.gov (United States)

    Mei, Nan; Guo, Lei; Fu, Peter P.; Fuscoe, James C.; Luan, Yang; Chen, Tao

    2018-01-01

    Comfrey has been consumed by humans as a vegetable and a tea and used as an herbal medicine for more than 2000 years. Comfrey, however, produces hepatotoxicity in livestock and humans and carcinogenicity in experimental animals. Comfrey contains as many as 14 pyrrolizidine alkaloids (PA), including 7-acetylintermedine, 7-acetyllycopsamine, echimidine, intermedine, lasiocarpine, lycopsamine, myoscorpine, symlandine, symphytine, and symviridine. The mechanisms underlying comfrey-induced genotoxicity and carcinogenicity are still not fully understood. The available evidence suggests that the active metabolites of PA in comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development. Genotoxicities attributed to comfrey and riddelliine (a representative genotoxic PA and a proven rodent mutagen and carcinogen) are discussed in this review. Both of these compounds induced similar profiles of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and similar mutation spectra. Further, the two agents share common mechanisms of drug metabolism and carcinogenesis. Overall, comfrey is mutagenic in liver, and PA contained in comfrey appear to be responsible for comfrey-induced toxicity and tumor induction. PMID:21170807

  9. Metabolism, genotoxicity, and carcinogenicity of comfrey.

    Science.gov (United States)

    Mei, Nan; Guo, Lei; Fu, Peter P; Fuscoe, James C; Luan, Yang; Chen, Tao

    2010-10-01

    Comfrey has been consumed by humans as a vegetable and a tea and used as an herbal medicine for more than 2000 years. Comfrey, however, produces hepatotoxicity in livestock and humans and carcinogenicity in experimental animals. Comfrey contains as many as 14 pyrrolizidine alkaloids (PA), including 7-acetylintermedine, 7-acetyllycopsamine, echimidine, intermedine, lasiocarpine, lycopsamine, myoscorpine, symlandine, symphytine, and symviridine. The mechanisms underlying comfrey-induced genotoxicity and carcinogenicity are still not fully understood. The available evidence suggests that the active metabolites of PA in comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development. Genotoxicities attributed to comfrey and riddelliine (a representative genotoxic PA and a proven rodent mutagen and carcinogen) are discussed in this review. Both of these compounds induced similar profiles of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and similar mutation spectra. Further, the two agents share common mechanisms of drug metabolism and carcinogenesis. Overall, comfrey is mutagenic in liver, and PA contained in comfrey appear to be responsible for comfrey-induced toxicity and tumor induction.

  10. Detection of genotoxic and non-genotoxic carcinogens in Xpc−/−p53+/− mice

    International Nuclear Information System (INIS)

    Melis, Joost P.M.; Speksnijder, Ewoud N.; Kuiper, Raoul V.; Salvatori, Daniela C.F.; Schaap, Mirjam M.; Maas, Saskia; Robinson, Joke; Verhoef, Aart; Benthem, Jan van; Luijten, Mirjam; Steeg, Harry van

    2013-01-01

    An accurate assessment of the carcinogenic potential of chemicals and pharmaceutical drugs is essential to protect humans and the environment. Therefore, substances are extensively tested before they are marketed to the public. Currently, the rodent two-year bioassay is still routinely used to assess the carcinogenic potential of substances. However, over time it has become clear that this assay yields false positive results and also has several economic and ethical drawbacks including the use of large numbers of animals, the long duration, and the high cost. The need for a suitable alternative assay is therefore high. Previously, we have proposed the Xpa*p53 mouse model as a very suitable alternative to the two-year bioassay. We now show that the Xpc*p53 mouse model preserves all the beneficial traits of the Xpa*p53 model for sub-chronic carcinogen identification and can identify both genotoxic and non-genotoxic carcinogens. Moreover, Xpc*p53 mice appear to be more responsive than Xpa*p53 mice towards several genotoxic and non-genotoxic carcinogens. Furthermore, Xpc*p53 mice are far less sensitive than Xpa*p53 mice for the toxic activity of DNA damaging agents and as such clearly respond in a similar way as wild type mice do. These advantageous traits of the Xpc*p53 model make it a better alternative for in vivo carcinogen testing than Xpa*p53. This pilot study suggests that Xpc*p53 mice are suited for routine sub-chronic testing of both genotoxic and non-genotoxic carcinogens and as such represent a suitable alternative to possibly replace the murine life time cancer bioassay. Highlights: ► The Xpc*p53 mouse model is able to identify genotoxic and non-genotoxic carcinogens. ► Time, animals and cost can be significantly reduced compared to the 2-year bioassay. ► Xpc*p53 mice are more advantageous for carcinogen identification than Xpa*p53 mice. ► Xpc*p53 mice exhibit a wild type response upon exposure to genotoxicants.

  11. Genotoxicity evaluation of the insecticide ethion in root of Allium ...

    African Journals Online (AJOL)

    USER

    2010-07-05

    Jul 5, 2010 ... In this study, the genotoxic effects of ethion were investigated in the mitotic cell division of Allium ... The use of plant root tips, particularly those of A. cepa and Vicia faba, as a bioassay test system for the genotoxicity of pesticides has shown extremely ..... the long run, even below the recommended dose.

  12. The cyto- and genotoxicity of organotin compounds is dependent on the cellular uptake capability

    International Nuclear Information System (INIS)

    Dopp, E.; Hartmann, L.M.; Recklinghausen, U. von; Florea, A.M.; Rabieh, S.; Shokouhi, B.; Hirner, A.V.; Obe, G.; Rettenmeier, A.W.

    2007-01-01

    Organotin compounds have been widely used as stabilizers and anti-fouling agents with the result that they are ubiquitously distributed in the environment. Organotins accumulate in the food chain and potential effects on human health are disquieting. It is not known as yet whether cell surface adsorption or accumulation within the cell, or indeed both is a prerequisite for the toxicity of organotin compounds. In this study, the alkylated tin derivatives monomethyltin trichloride (MMT), dimethyltin dichloride (DMT), trimethyltin chloride (TMT) and tetramethyltin (TetraMT) were investigated for cyto- and genotoxic effects in CHO-9 cells in relation to the cellular uptake. To identify genotoxic effects, induction of micronuclei (MN), chromosome aberrations (CA) and sister chromatid exchanges (SCE) were analyzed and the nuclear division index (NDI) was calculated. The cellular uptake was assessed using ICP-MS analysis. The toxicity of the tin compounds was also evaluated after forced uptake by electroporation. Our results show that uptake of the organotin compounds was generally low but dose-dependent. Only weak genotoxic effects were observed after exposure of cells to DMT and TMT. MMT and TetraMT were negative in the test systems. After forced uptake by electroporation MMT, DMT and TMT induced significant DNA damage at non-cytotoxic concentrations. The results presented here indicate a considerable toxicological potential of some organotin species but demonstrate clearly that the toxicity is modulated by the cellular uptake capability

  13. Eco- and genotoxicity profiling of a rapeseed biodiesel using a battery of bioassays.

    Science.gov (United States)

    Eck-Varanka, Bettina; Kováts, Nora; Horváth, Eszter; Ferincz, Árpád; Kakasi, Balázs; Nagy, Szabolcs Tamás; Imre, Kornélia; Paulovits, Gábor

    2018-04-30

    Biodiesel is considered an important renewable energy source but still there is some controversy about its environmental toxicity, especially to aquatic life. In our study, the toxicity of water soluble fraction of biodiesel was evaluated in relatively low concentrations using a battery of bioassays: Vibrio fischeri bioluminescence inhibition, Sinapis alba root growth inhibition, Daphnia magna immobilization, boar semen live/dead ratio and DNA fragmentation and Unio pictorum micronucleus test. While the S. alba test indicated nutritive (stimulating) effect of the sample, the biodiesel exerted toxic effect in the aquatic tests. D. magna was the most sensitive with EC 50 value of 0.0226%. For genotoxicity assessment, the mussel micronucleus test (MNT) was applied, detecting considerable genotoxic potential of the biodiesel sample: it elucidated micronuclei formation already at low concentration of 3.3%. Although this test has never been employed in biodiesel eco/genotoxicity assessments, it seems a promising tool, based on its appropriate sensitivity, and representativity. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Evaluation of the genotoxicity of cellulose nanofibers.

    Science.gov (United States)

    de Lima, Renata; Oliveira Feitosa, Leandro; Rodrigues Maruyama, Cintia; Abreu Barga, Mariana; Yamawaki, Patrícia Cristina; Vieira, Isolda Jesus; Teixeira, Eliangela M; Corrêa, Ana Carolina; Caparelli Mattoso, Luiz Henrique; Fernandes Fraceto, Leonardo

    2012-01-01

    Agricultural products and by products provide the primary materials for a variety of technological applications in diverse industrial sectors. Agro-industrial wastes, such as cotton and curaua fibers, are used to prepare nanofibers for use in thermoplastic films, where they are combined with polymeric matrices, and in biomedical applications such as tissue engineering, amongst other applications. The development of products containing nanofibers offers a promising alternative for the use of agricultural products, adding value to the chains of production. However, the emergence of new nanotechnological products demands that their risks to human health and the environment be evaluated. This has resulted in the creation of the new area of nanotoxicology, which addresses the toxicological aspects of these materials. Contributing to these developments, the present work involved a genotoxicological study of different nanofibers, employing chromosomal aberration and comet assays, as well as cytogenetic and molecular analyses, to obtain preliminary information concerning nanofiber safety. The methodology consisted of exposure of Allium cepa roots, and animal cell cultures (lymphocytes and fibroblasts), to different types of nanofibers. Negative controls, without nanofibers present in the medium, were used for comparison. The nanofibers induced different responses according to the cell type used. In plant cells, the most genotoxic nanofibers were those derived from green, white, and brown cotton, and curaua, while genotoxicity in animal cells was observed using nanofibers from brown cotton and curaua. An important finding was that ruby cotton nanofibers did not cause any significant DNA breaks in the cell types employed. This work demonstrates the feasibility of determining the genotoxic potential of nanofibers derived from plant cellulose to obtain information vital both for the future usage of these materials in agribusiness and for an understanding of their environmental

  15. Cells behaviors and genotoxicity on topological surface

    International Nuclear Information System (INIS)

    Yang, N.; Yang, M.K.; Bi, S.X.; Chen, L.; Zhu, Z.Y.; Gao, Y.T.; Du, Z.

    2013-01-01

    To investigate different cells behaviors and genotoxicity, which were driven by specific microenvironments, three patterned surfaces (pillars, wide grooves and narrow grooves) and one smooth surface were prepared by template-based technique. Vinculin is a membrane-cytoskeletal protein in focal adhesion plaques and associates with cell–cell and cell–matrix junctions, which can promote cell adhesion and spreading. The immunofluorescence staining of vinculin revealed that the narrow grooves patterned substrate was favorable for L929 cell adhesion. For cell multiplication, the narrow grooves surface was fitted for the proliferation of L929, L02 and MSC cells, the pillars surface was only in favor of L929 cells to proliferate during 7 days of cell cultivation. Cell genetic toxicity was evaluated by cellular micronuclei test (MNT). The results indicated that topological surfaces were more suitable for L929 cells to proliferate and maintain the stability of genome. On the contrary, the narrow grooves surface induced higher micronuclei ratio of L02 and MSC cells than other surfaces. With the comprehensive results of cell multiplication and MNT, it was concluded that the wide grooves surface was best fitted for L02 cells to proliferate and have less DNA damages, and the smooth surface was optimum for the research of MSC cells in vitro. - Highlights: • Different cells behaviors on microstructure surfaces were discussed in this paper. • The expression of cell protein of Vinculin was studied in this research. • Cellular micronuclei test was applied to evaluate cells' genotoxicity. • Cell genotoxicity was first studied in the research field of topological surfaces

  16. Evaluation of perfluorooctanoate for potential genotoxicity

    Directory of Open Access Journals (Sweden)

    John L. Butenhoff

    2014-01-01

    Full Text Available Perfluorooctanoate (PFOA is a fully fluorinated eight-carbon fatty acid analog with exceptional stability toward degradation that has been used as an industrial surfactant and has been detected in environmental and biological matrices. Exposures to PFOA in the workplace and in the environment have continuously stimulated investigations into its potential human health hazards. In this article, the results of fifteen unpublished genotoxicity assays conducted with perfluorooctanoate (as either the linear or linear/branched ammonium salt (APFO or the linear/branched sodium salt are reported and include: seven mutation assays (three in vitro reverse mutation assays with histidine auxotrophic strains of Salmonella typhimurium, two in vitro reverse mutation assays with the tryptophan auxotrophic Escherichia coli WP2uvr strain, one in vitro mitotic recombination (gene conversion assay with Saccharomyces cerevisiae D4, and an in vitro Chinese hamster ovary (CHO HGPRT forward mutation assay; seven studies to assess potential for chromosomal damage (three in vitro CHO chromosomal aberration studies, an in vitro human whole blood lymphocyte chromosomal aberration study, and three in vivo mouse micronucleus assays; and an in vitro C3H 10T1/2 cell transformation assay. Although PFOA has not been demonstrated to be metabolized, all in vitro assays were conducted both in the presence and in the absence of a mammalian hepatic microsomal activation system. These assays were originally described in twelve contract laboratory reports which have been available via the United States Environmental Protection Agency public docket (Administrative Record 226 for over a decade; however, the details of these assays have not been published previously in the open scientific literature. With the exception of limited positive findings at high and cytotoxic concentrations in some assay trials which reflected the likely consequence of cytotoxic disruption of normal cellular

  17. Cytotoxicity and genotoxicity of calcium silicate-based cements on an osteoblast lineage

    Directory of Open Access Journals (Sweden)

    Ana Lívia GOMES-CORNÉLIO

    2016-01-01

    Full Text Available Abstract Several calcium silicate-based biomaterials have been developed in recent years, in addition to Mineral Trioxide Aggregate (MTA. The aim of this study was to evaluate the cytotoxicity, genotoxicity and apoptosis/necrosis in human osteoblast cells (SAOS-2 of pure calcium silicate-based cements (CSC and modified formulations: modified calcium silicate-based cements (CSCM and three resin-based calcium silicate cements (CSCR1 (CSCR 2 (CSCR3. The following tests were performed after 24 hours of cement extract exposure: methyl-thiazolyl tetrazolium (MTT, apoptosis/necrosis assay and comet assay. The negative control (CT- was performed with untreated cells, and the positive control (CT+ used hydrogen peroxide. The data for MTT and apoptosis were submitted to analysis of variance and Bonferroni’s posttest (p < 0.05, and the data for the comet assay analysis, to the Kruskal-Wallis and Dunn tests (p < 0.05. The MTT test showed no significant difference among the materials in 2 mg/mL and 10 mg/mL concentrations. CSCR3 showed lower cell viability at 10 mg/mL. Only CSC showed lower cell viability at 50 mg/mL. CSCR1, CSCR2 and CSCR3 showed a higher percentage of initial apoptosis than the control in the apoptosis test, after 24 hours exposure. The same cements showed no genotoxicity in the concentration of 2 mg/mL, with the comet assay. CSC and CSCR2 were also not genotoxic at 10 mg/mL. All experimental materials showed viability with MTT. CSC and CSCR2 presented a better response to apoptosis and genotoxicity evaluation in the 10 mg/mL concentration, and demonstrated a considerable potential for use as reparative materials.

  18. Genotoxicity Expert Panel review: weight of evidence evaluation of the genotoxicity of glyphosate, glyphosate-based formulations, and aminomethylphosphonic acid.

    Science.gov (United States)

    Brusick, David; Aardema, Marilyn; Kier, Larry; Kirkland, David; Williams, Gary

    2016-09-01

    In 2015, the International Agency for Research on Cancer (IARC) published a monograph concluding there was strong evidence for genotoxicity of glyphosate and glyphosate formulations and moderate evidence for genotoxicity of the metabolite aminomethylphosphonic acid (AMPA). These conclusions contradicted earlier extensive reviews supporting the lack of genotoxicity of glyphosate and glyphosate formulations. The IARC Monograph concluded there was strong evidence of induction of oxidative stress by glyphosate, glyphosate formulations, and AMPA. The Expert Panel reviewed the genotoxicity and oxidative stress data considered in the IARC Monograph, together with other available data not considered by IARC. The Expert Panel defined and used a weight of evidence (WoE) approach that included ranking of studies and endpoints by the strength of their linkage to events associated with carcinogenic mechanisms. Importantly, the Expert Panel concluded that there was sufficient information available from a very large number of regulatory genotoxicity studies that should have been considered by IARC. The WoE approach, the inclusion of all relevant regulatory studies, and some differences in interpretation of individual studies led to significantly different conclusions by the Expert Panel compared with the IARC Monograph. The Expert Panel concluded that glyphosate, glyphosate formulations, and AMPA do not pose a genotoxic hazard and the data do not support the IARC Monograph genotoxicity evaluation. With respect to carcinogenicity classification and mechanism, the Expert Panel concluded that evidence relating to an oxidative stress mechanism of carcinogenicity was largely unconvincing and that the data profiles were not consistent with the characteristics of genotoxic carcinogens.

  19. Genotoxicity tests on D-tagatose.

    Science.gov (United States)

    Kruger, C L; Whittaker, M H; Frankos, V H

    1999-04-01

    D-tagatose is a low-calorie sweetener that tastes like sucrose. Its genotoxic potential was examined in five standard assays: the Ames Salmonella typhimurium reverse mutation assay, the Escherichia coli/mammalian microsome assay, a chromosomal aberration assay in Chinese hamster ovary cells, a mouse lymphoma forward mutation assay, and an in vivo mouse micronucleus assay. D-tagatose was not found to increase the number of revertants per plate relative to vehicle controls in either the S. typhimurium tester strains or the WP2uvrA- tester strain with or without metabolic activation at doses up to 5000 microg/plate. No significant increase in Chinese hamster ovary cells with chromosomal aberrations was observed at concentrations up to 5000 microg/ml with or without metabolic activation. D-tagatose was not found to increase the mutant frequency in mouse lymphoma L5178Y cells with or without metabolic activation up to concentrations of 5000 microg/ml. D-tagatose caused no significant increase in micronuclei in bone marrow polychromatic erythrocytes at doses up to 5000 mg/kg. D-tagatose was not found to be genotoxic under the conditions of any of the assays described above. Copyright 1999 Academic Press.

  20. Current methods in risk assessment of genotoxic chemicals.

    Science.gov (United States)

    Cartus, Alexander; Schrenk, Dieter

    2017-08-01

    Chemical contaminants and residues are undesired chemicals occurring in consumer products such as food and drugs, at the workplace and in the environment, i.e. in air, soil and water. These compounds can be detected even at very low concentrations and lead frequently to considerable concerns among consumers and in the media. Thus it is a major challenge for modern toxicology to provide transparent and versatile tools for the risk assessment of such compounds in particular with respect to human health. Well-known examples of toxic contaminants are dioxins or mercury (in the environment), mycotoxins (from infections by molds) or acrylamide (from thermal treatment of food). The process of toxicological risk assessment of such chemicals is based on i) the knowledge of their contents in food, air, water etc., ii) the routes and extent of exposure of humans, iii) the toxicological properties of the compound, and, iv) its mode(s) of action. In this process quantitative dose-response relationships, usually in experimental animals, are of outstanding importance. For a successful risk assessment, in particular of genotoxic chemicals, several conditions and models such as the Margin of Exposure (MoE) approach or the Threshold of Toxicological Concern (TTC) concept exist, which will be discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. The Vulnerabilities of Orphaned Children Participating in Research: A Critical Review and Factors for Consideration for Participation in Biomedical and Behavioral Research

    Science.gov (United States)

    Thompson, Rachel T.; Meslin, Eric M.; Braitstein, Paula K. A.; Nyandiko, Winstone M.; Ayaya, Samuel O.; Vreeman, Rachel C.

    2013-01-01

    Orphans are a subpopulation with a unique set of additional vulnerabilities. Increasing focus on children’s rights, pediatric global health, and pediatric research makes it imperative to recognize and address unique vulnerabilities of orphaned children. This paper describes the unique vulnerabilities of the orphaned pediatric population and offers a structured set of factors that require consideration when including orphans in biomedical research. Pediatric orphans are particularly vulnerable due to decreased economic resources, psychosocial instability, increased risk of abuse, and delayed/decreased access to healthcare. These vulnerabilities are significant. By carefully considering each issue in a population in a culturally specific and study-specific manner, researchers can make valuable contributions to the overall health and well-being of this uniquely vulnerable population. PMID:23086048

  2. Involvement of mismatch repair proteins in adaptive responses induced by N-methyl-N'-nitro-N-nitrosoguanidine against {gamma}-induced genotoxicity in human cells

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Ayumi; Sakamoto, Yasuteru; Masumura, Kenichi; Honma, Masamitsu [Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan); Nohmi, Takehiko, E-mail: nohmi@nihs.go.jp [Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan)

    2011-08-01

    Highlights: {yields} Health effects of radiation should be evaluated in combination with chemicals. {yields} Here, we show that MNNG suppresses radiation-induced genotoxicity in human cells. {yields} Mismatch repair proteins play critical roles in the apparent adaptive responses. {yields} Chemical exposure may modulate radiation-induced genotoxicity in humans. - Abstract: As humans are exposed to a variety of chemical agents as well as radiation, health effects of radiation should be evaluated in combination with chemicals. To explore combined genotoxic effects of radiation and chemicals, we examined modulating effects of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a direct-acting methylating agent, against genotoxicity of {gamma}-radiation. Human lymphoblastoid TK6 cells and its mismatch-deficient derivative, i.e., MT1 cells, were treated with MNNG for 24 h before they were exposed to {gamma}-irradiation at a dose of 1.0 Gy, and the resulting genotoxicity was examined. In TK6 cells, the pretreatments with MNNG at low doses suppressed frequencies of the thymidine kinase (TK) gene mutation and micronucleus (MN) formation induced by {gamma}-irradiation and thus the dose responses of TK and MN assays were U-shaped along with the pretreatment doses of MNNG. In contrast, the genotoxic effects of MNNG and {gamma}-irradiation were additive in MT1 cells and the frequencies of TK mutations and MN induction increased along with the doses of MNNG. Apoptosis induced by {gamma}-radiation was suppressed by the pretreatments in TK6 cells, but not in MT1 cells. The expression of p53 was induced and cell cycle was delayed at G2/M phase in TK6, but not in MT1 cells, by the treatments with MNNG. These results suggest that pretreatments of MNNG at low doses suppress genotoxicity of {gamma}-radiation in human cells and also that mismatch repair proteins are involved in the apparent adaptive responses.

  3. Genotoxicity of copper oxide nanoparticles with different surface chemistry on rat bone marrow mesenchymal stem cells

    DEFF Research Database (Denmark)

    Zhang, Wenjing; Jiang, Pengfei; Chen, Wei

    2016-01-01

    The surface chemistry of nanoparticles (NPs) is one of the critical factors determining their cellular responses. In this study, the cytotoxicity and genotoxicity of copper oxide (CuO) NPs with a similar size but different surface chemistry to rat bone marrow mesenchymal stem cells (MSCs) were......V and showed a similar tendency to form agglomerates with a size of ∼200 nm in cell culture environment. The cytotoxicity of CuO NPs to MSCs at various concentrations and incubation periods were firstly evaluated. The CuO NPs showed dose-dependent and time-dependent toxicity to MSCs, and their surface...

  4. Genotoxicity in the eyes of bystander cells

    International Nuclear Information System (INIS)

    Hei, Tom K.; Persaud, Rudranath; Zhou, Hongning; Suzuki, Masao

    2004-01-01

    The controversial use of a linear, no threshold extrapolation model for low dose risk assessment has become even more so in light of the recent reports on the bystander phenomenon. The answer to the question as to which of the two phenomena, bystander versus adaptive response, is more important has practical implication in terms of low dose radiation risk assessment. In this review, genotoxicity is used as an endpoint to introduce the two phenomena, provide some insight into the mechanisms of bystander effect and to bridge the two low dose phenomena which operate in opposite directions: the bystander effect tends to exaggerate the effect at low doses, by communicating damage from hit to non-hit cells whereas the adaptive response confers resistance to a subsequent challenging dose by an initial low priming dose

  5. The interaction between milk and beef production and emissions from land use change – critical considerations in life cycle assessment and carbon footprint studies of milk

    DEFF Research Database (Denmark)

    Flysjö, Anna Maria; Cederberg, Christel; Henriksson, Maria

    2012-01-01

    Two most critical factors to address in environmental system analysis of future milk production are 1) the link between milk and beef production, and 2) the competition for land, possibly leading to land use change (LUC) with greenhouse gas (GHG) emissions and loss of biodiversity as important...... is investigated for 23 dairy farms (both organic and conventional) in Sweden. Use of a fixed allocation factor of 90% (based on economic value) indicates a reduction in CF with increased milk yield, while no correlation can be noted when system expansion is applied. The average CF for two groups of farms, organic...... and high yielding conventional, is also calculated. When conducting system expansion the CF is somewhat lower for the organic farms (which have a lower milk yield per cow, but more meat per kg milk), but when a 90% allocation factor is used, the CF is somewhat higher for the organic farms compared...

  6. The impact of fire suppression tasks on firefighter hydration: a critical review with consideration of the utility of reported hydration measures.

    Science.gov (United States)

    Walker, Adam; Pope, Rodney; Orr, Robin Marc

    2016-01-01

    Firefighting is a highly stressful occupation with unique physical challenges, apparel and environments that increase the potential for dehydration. Dehydration leaves the firefighter at risk of harm to their health, safety and performance. The purpose of this review was to critically analyse the current literature investigating the impact of fighting 'live' fires on firefighter hydration. A systematic search was performed of four electronic databases for relevant published studies investigating the impact of live fire suppression on firefighter hydration. Study eligibility was assessed using strict inclusion and exclusion criteria. The included studies were critically appraised using the Downs and Black protocol and graded according to the Kennelly grading system. Ten studies met the eligibility criteria for this review. The average score for methodological quality was 55 %, ranging from 50 % ('fair' quality) to 61 % ('good' quality) with a 'substantial agreement' between raters ( k  = .772). Wildfire suppression was considered in five studies and structural fire suppression in five studies. Results varied across the studies, reflecting variations in outcome measures, hydration protocols and interventions. Three studies reported significant indicators of dehydration resulting from structural fire suppression, while two studies found mixed results, with some measures indicating dehydration and other measures an unchanged hydration status. Three studies found non-significant changes in hydration resulting from wildfire firefighting and two studies found significant improvements in markers of hydration. Ad libitum fluid intake was a common factor across the studies finding no, or less severe, dehydration. The evidence confirms that structural and wildfire firefighting can cause dehydration. Ad libitum drinking may be sufficient to maintain hydration in many wildfire environments but possibly not during intense, longer duration, hot structural fire operations

  7. Genotoxicity Screening of Industrial Effluents using Onion bulbs ...

    African Journals Online (AJOL)

    Michael Horsfall

    ABSTRACT: The potential cytotoxicity and genotoxicity of three industrial wastewaters (brewery .... National recommended water quality criteria – correction; cWorld Health Organisation (1996). ..... Industrial Pollution Policy Management Study.

  8. Determination of heavy metals and genotoxicity of water from an ...

    African Journals Online (AJOL)

    Determination of heavy metals and genotoxicity of water from an artesian well ... do Amaral, Vanessa Marques de Oliveira Moraes, Luciana Pereira Silva ... environmental interest because it is the most important zinc producer district of Brazil.

  9. Genotoxic Effect of Atrazine, Arsenic, Cadmium and Nitrate ...

    African Journals Online (AJOL)

    Atrazine has clastogenic effects and may also act as tumor promoter as it induces the aromatase enzyme. ... bladder cancer. This study ... in MCF-10A cells, suggesting that estrogen receptor modulated the genotoxicity of estrogen. Cd caused ...

  10. In vitro evaluation of mutagenicity and genotoxicity of sitagliptin ...

    African Journals Online (AJOL)

    Keywords: Sitagliptin, Artificial sweeteners, Comet assay, DNA damage, Ames assay, Genotoxicity,. Mutagenicity. Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus,. International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, EBSCO, African.

  11. Titanium dioxide nanoparticles cause genotoxicity in human lung epithelial cells

    Science.gov (United States)

    The use of engineered nanoparticles in consumer products is steadily increasing. However, the health effects of exposure to these nanoparticles are not thoroughly understood. This study investigated the genotoxicity of six titanium dioxide and two cerium oxide nanoparticles of va...

  12. THE GENOTOXICITY OF AMBIENT OUTDOOR AIR, A REVIEW: SALMONELLA MUTAGENICITY

    Science.gov (United States)

    The genotoxicity of ambient outdoor air, a review: Salmonella mutagenicityAbstractMutagens in urban air pollution come from anthropogenic sources (especially combustion sources) and are products of airborne chemical reactions. Bacterial mutation tests have been used ...

  13. Genotoxicity evaluation of alpha-linolenic acid-diacylglycerol oil

    Directory of Open Access Journals (Sweden)

    Hiroshi Honda

    Full Text Available The alpha-linolenic acid (ALA-diacylglycerol (DAG oil is an edible oil enriched with DAG (>80% and ALA (>50%. Although DAG oil, which mainly consists of oleic and linoleic acids has no genotoxic concerns, the fatty acid composition could affect the chemical property of DAG. Therefore, the purpose of this study was to evaluate the genotoxicity of ALA-DAG oil using standard genotoxicity tests in accordance with the OECD guidelines. ALA-DAG oil showed negative results in the bacterial reverse mutation test (Ames test and in vitro micronucleus test in cultured Chinese hamster lung cells with and without metabolic activation, and in the in vivo bone marrow micronucleus test in mice. Our results did not show any genotoxicity, suggesting that the fatty acid composition had no deleterious effects. We conclude that ALA-DAG oil had no genotoxicity concerns under the testing conditions. Keywords: Alpha-linolenic acid-rich diacylglycerol, Diacylglycerol, Alpha-linolenic acid, Fatty acid composition, Genotoxicity

  14. Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential.

    Science.gov (United States)

    Walker, Claire-Dominique; Bath, Kevin G; Joels, Marian; Korosi, Aniko; Larauche, Muriel; Lucassen, Paul J; Morris, Margaret J; Raineki, Charlis; Roth, Tania L; Sullivan, Regina M; Taché, Yvette; Baram, Tallie Z

    2017-09-01

    The immediate and long-term effects of exposure to early life stress (ELS) have been documented in humans and animal models. Even relatively brief periods of stress during the first 10 days of life in rodents can impact later behavioral regulation and the vulnerability to develop adult pathologies, in particular an impairment of cognitive functions and neurogenesis, but also modified social, emotional, and conditioned fear responses. The development of preclinical models of ELS exposure allows the examination of mechanisms and testing of therapeutic approaches that are not possible in humans. Here, we describe limited bedding and nesting (LBN) procedures, with models that produce altered maternal behavior ranging from fragmentation of care to maltreatment of infants. The purpose of this paper is to discuss important issues related to the implementation of this chronic ELS procedure and to describe some of the most prominent endpoints and consequences, focusing on areas of convergence between laboratories. Effects on the hypothalamic-pituitary adrenal (HPA) axis, gut axis and metabolism are presented in addition to changes in cognitive and emotional functions. Interestingly, recent data have suggested a strong sex difference in some of the reported consequences of the LBN paradigm, with females being more resilient in general than males. As both the chronic and intermittent variants of the LBN procedure have profound consequences on the offspring with minimal external intervention from the investigator, this model is advantageous ecologically and has a large translational potential. In addition to the direct effect of ELS on neurodevelopmental outcomes, exposure to adverse early environments can also have intergenerational impacts on mental health and function in subsequent generation offspring. Thus, advancing our understanding of the effect of ELS on brain and behavioral development is of critical concern for the health and wellbeing of both the current

  15. Comparison of the in vivo and in vitro genotoxicity of glyphosate isopropylamine salt in three different organisms.

    Science.gov (United States)

    Alvarez-Moya, Carlos; Silva, Mónica Reynoso; Ramírez, Carlos Valdez; Gallardo, David Gómez; Sánchez, Rafael León; Aguirre, Alejandro Canales; Velasco, Alfredo Feria

    2014-03-01

    There is considerable controversy with regard to the genotoxicity of glyphosate, with some reports stating that this compound is non-toxic for fish, birds and mammals. In this work, we used the comet assay to examine the genotoxicity of glyphosate isopropylamine (0.7, 7, 70 and 700 μM) in human lymphocytes, erythrocytes of Oreochromis niloticus and staminal nuclei of Tradescantia (4430) in vitro and in vivo. Cells, nuclei and fish that had and had not been exposed to 5 mM N-nitrosodiethylamine (NDEA) were used as positive and negative controls, respectively. Significant (p cell types and organisms tested. Human lymphocytes and Tradescantia hairs showed lower genetic damage in vivo compared to in vitro, possibly because of efficient metabolization of the herbicide. In O. niloticus erythrocytes, significant (p cells and organisms studied at concentrations of 0.7-7 μM.

  16. Chapter 2. Surge capacity and infrastructure considerations for mass critical care. Recommendations and standard operating procedures for intensive care unit and hospital preparations for an influenza epidemic or mass disaster.

    Science.gov (United States)

    Hick, John L; Christian, Michael D; Sprung, Charles L

    2010-04-01

    To provide recommendations and standard operating procedures for intensive care unit (ICU) and hospital preparations for a mass disaster or influenza epidemic with a specific focus on surge capacity and infrastructure considerations. Based on a literature review and expert opinion, a Delphi process was used to define the essential topics including surge capacity and infrastructure considerations. Key recommendations include: (1) hospitals should increase their ICU beds to the maximal extent by expanding ICU capacity and expanding ICUs into other areas; (2) hospitals should have appropriate beds and monitors for these expansion areas; hospitals should develop contingency plans at the facility and government (local, state, provincial, national) levels to provide additional ventilators; (3) hospitals should develop a phased staffing plan (nursing and physician) for ICUs that provides sufficient patient care supervision during contingency and crisis situations; (4) hospitals should provide expert input to the emergency management personnel at the hospital both during planning for surge capacity as well as during response; (5) hospitals should assure that adequate infrastructure support is present to support critical care activities; (6) hospitals should prioritize locations for expansion by expanding existing ICUs, using postanesthesia care units and emergency departments to capacity, then step-down units, large procedure suites, telemetry units and finally hospital wards. Judicious planning and adoption of protocols for surge capacity and infrastructure considerations are necessary to optimize outcomes during a pandemic.

  17. Genotoxic damage in auto body shop workers.

    Science.gov (United States)

    Siebel, Anna Maria; Basso da Silva, Luciano

    2010-10-01

    Some studies have shown increased DNA damage among car painters, but other professionals working in auto body and paint shops have not been extensively assessed. The aim of this study was to assess DNA damage in different types of auto body shop workers by measuring micronucleus (MN) levels in exfoliated buccal cells. The mean number of cells with MN per 2000 exfoliated buccal cells was analyzed in three groups of male workers: auto body repair technicians, painters, and office workers (control group). All participants answered a questionnaire inquiring about age, smoking habits, alcohol consumption, work practices, occupational exposure time, job activities, and use of protective equipment. The mean number of cells with MN was 3.50 ± 1.50 in auto body painters, 3.91 ± 2.10 in auto body repair technicians, and 0.80 ± 0.78 in office workers, with a significant difference between the control group and the two other groups (p = 0.0001). Age, occupational exposure time, use of protective masks, alcohol consumption, and smoking habit did not affect MN results. The findings indicate that technicians and painters working in auto body shops are at risk for genotoxic damage, while office workers seem to be protected.

  18. Genotoxic effects of zinc oxide nanoparticles

    Science.gov (United States)

    Heim, Julia; Felder, Eva; Tahir, Muhammad Nawaz; Kaltbeitzel, Anke; Heinrich, Ulf Ruediger; Brochhausen, Christoph; Mailänder, Volker; Tremel, Wolfgang; Brieger, Juergen

    2015-05-01

    The potential toxicity of nanoparticles has currently provoked public and scientific discussions, and attempts to develop generally accepted handling procedures for nanoparticles are under way. The investigation of the impact of nanoparticles on human health is overdue and reliable test systems accounting for the special properties of nanomaterials must be developed. Nanoparticular zinc oxide (ZnO) may be internalised through ambient air or the topical application of cosmetics, only to name a few, with unpredictable health effects. Therefore, we analysed the determinants of ZnO nanoparticle (NP) genotoxicity. ZnO NPs (15-18 nm in diameter) were investigated at concentrations of 0.1, 10 and 100 μg mL-1 using the cell line A549. Internalised NPs were only infrequently detectable by TEM, but strongly increased Zn2+ levels in the cytoplasm and even more in the nuclear fraction, as measured by atom absorption spectroscopy, indicative of an internalised zinc and nuclear accumulation. We observed a time and dosage dependent reduction of cellular viability after ZnO NP exposure. ZnCl2 exposure to cells induced similar impairments of cellular viability. Complexation of Zn2+ with diethylene triamine pentaacetic acid (DTPA) resulted in the loss of toxicity of NPs, indicating the relevant role of Zn2+ for ZnO NP toxicity. Foci analyses showed the induction of DNA double strand breaks (DSBs) by ZnO NPs and increased intracellular reactive oxygen species (ROS) levels. Treatment of the cells with the ROS scavenger N-acetyl-l-cysteine (NAC) resulted in strongly decreased intracellular ROS levels and reduced DNA damage. However, a slow increase of ROS after ZnO NP exposure and reduced but not quashed DSBs after NAC-treatment suggest that Zn2+ may exert genotoxic activities without the necessity of preceding ROS-induction. Our data indicate that ZnO NP toxicity is a result of cellular Zn2+ intake. Subsequently increased ROS-levels cause DNA damage. However, we found evidence for

  19. Evaluation of Cytotoxicity and Genotoxicity of Acacia aroma Leaf Extracts

    Directory of Open Access Journals (Sweden)

    C. M. Mattana

    2014-01-01

    Full Text Available Acacia aroma, native plant from San Luis, Argentina, is commonly used as antiseptic and for healing of wounds. The present study was conducted to investigate the in vitro cytotoxicity and genotoxicity of hot aqueous extract (HAE and ethanolic extract (EE of A. aroma. The cytotoxic activity was assayed by neutral red uptake assay on Vero cell. Cell treatment with a range from 100 to 5000 μg/mL of HAE and EE showed that 500 μg/mL and 100 μg/mL were the maximum noncytotoxic concentrations, respectively. The CC50 was 658 μg/mL for EE and 1020 μg/mL for HAE. The genotoxicity was tested by the single-cell gel electrophoresis comet assay. The results obtained in the evaluation of DNA cellular damage exposed to varied concentrations of the HAE showed no significant genotoxic effect at range of 1–20 mg/mL. The EE at 20 mg/mL showed moderate genotoxic effect related to the increase of the DNA percentage contained in tail of the comet; DNA was classified in category 2. At concentrations below 5 mg/mL, the results of cytotoxicity and genotoxicity of aqueous and ethanolic extracts of Acacia aroma guarantee the safety at cell and genomic level. However further studies are needed for longer periods including animal models to confirm the findings.

  20. Distinct Functional Domains of Ubc9 Dictate Cell Survival and Resistance to Genotoxic Stress

    Science.gov (United States)

    van Waardenburg, Robert C. A. M.; Duda, David M.; Lancaster, Cynthia S.; Schulman, Brenda A.; Bjornsti, Mary-Ann

    2006-01-01

    Covalent modification with SUMO alters protein function, intracellular localization, or protein-protein interactions. Target recognition is determined, in part, by the SUMO E2 enzyme, Ubc9, while Siz/Pias E3 ligases may facilitate select interactions by acting as substrate adaptors. A yeast conditional Ubc9P123L mutant was viable at 36°C yet exhibited enhanced sensitivity to DNA damage. To define functional domains in Ubc9 that dictate cellular responses to genotoxic stress versus those necessary for cell viability, a 1.75-Å structure of yeast Ubc9 that demonstrated considerable conservation of backbone architecture with human Ubc9 was solved. Nevertheless, differences in side chain geometry/charge guided the design of human/yeast chimeras, where swapping domains implicated in (i) binding residues within substrates that flank canonical SUMOylation sites, (ii) interactions with the RanBP2 E3 ligase, and (iii) binding of the heterodimeric E1 and SUMO had distinct effects on cell growth and resistance to DNA-damaging agents. Our findings establish a functional interaction between N-terminal and substrate-binding domains of Ubc9 and distinguish the activities of E3 ligases Siz1 and Siz2 in regulating cellular responses to genotoxic stress. PMID:16782883

  1. Genotoxicity test of Maytenus rigida and Aristolochia birostris in the radicular meristem of the onion, Allium cepa

    Directory of Open Access Journals (Sweden)

    Sandra S. Mendes

    2011-09-01

    Full Text Available Medicinal plants are an important source of treatment for many ailments, although little is known of the potential genotoxic effects of most species. In the present study, two species from diverse and medicinally important genera - Maytenus rigida Mart., Celastraceae, and Aristolochia birostris Ducht, Aristolochiaceae - were analyzed to identify potentially significant secondary metabolites and the possible effects of their aqueous and alcoholic extracts on cell division in the onion root stem (genotoxicity test. The phytochemical testing revealed the presence of a number of potentially important secondary compounds in both species, including phenols, flavonoids, triterpenoids, steroids, and saponins. In the genotoxicity tests, no chromosomal abnormalities of any kind were observed in either species. In the case of M. rigida, a significant increase in mitotic activity was observed at the highest concentration. No significant tendency was recorded in A. birostris, although a considerable increase in the prophase was observed at all concentrations of the alcoholic extract. The triterpenoid content of both species may be especially important from a medicinal viewpoint, although recent findings on the carcinogenic potential of Aristolochia extracts demands caution in the interpretation of the results, and the need for further research.

  2. Genotoxicity test of Maytenus rigida and Aristolochia birostris in the radicular meristem of the onion, Allium cepa

    Directory of Open Access Journals (Sweden)

    Sandra S. Mendes

    2012-02-01

    Full Text Available Medicinal plants are an important source of treatment for many ailments, although little is known of the potential genotoxic effects of most species. In the present study, two species from diverse and medicinally important genera - Maytenus rigida Mart., Celastraceae, and Aristolochia birostris Ducht, Aristolochiaceae - were analyzed to identify potentially significant secondary metabolites and the possible effects of their aqueous and alcoholic extracts on cell division in the onion root stem (genotoxicity test. The phytochemical testing revealed the presence of a number of potentially important secondary compounds in both species, including phenols, flavonoids, triterpenoids, steroids, and saponins. In the genotoxicity tests, no chromosomal abnormalities of any kind were observed in either species. In the case of M. rigida, a significant increase in mitotic activity was observed at the highest concentration. No significant tendency was recorded in A. birostris, although a considerable increase in the prophase was observed at all concentrations of the alcoholic extract. The triterpenoid content of both species may be especially important from a medicinal viewpoint, although recent findings on the carcinogenic potential of Aristolochia extracts demands caution in the interpretation of the results, and the need for further research.

  3. ITER plasma facing materials. Some critical considerations

    International Nuclear Information System (INIS)

    Barabash, V.; Dietz, K.J.; Federici, G.; Janeschitz, G.; Matera, R.; Tanaka, S.

    1995-01-01

    The description of current status with the choice of materials for ITER plasma facing components is presented. The main problem with lifetime of divertor elements is the particle and energy-induced erosion of armour materials. A solution for the first operation phase consists in using Be as an armour for the first wall and the divertor, however other possible materials (e.g. W) could be considered. (orig.)

  4. Genotoxicity of Superparamagnetic Iron Oxide Nanoparticles in Granulosa Cells

    Directory of Open Access Journals (Sweden)

    Marina Pöttler

    2015-11-01

    Full Text Available Nanoparticles that are aimed at targeting cancer cells, but sparing healthy tissue provide an attractive platform of implementation for hyperthermia or as carriers of chemotherapeutics. According to the literature, diverse effects of nanoparticles relating to mammalian reproductive tissue are described. To address the impact of nanoparticles on cyto- and genotoxicity concerning the reproductive system, we examined the effect of superparamagnetic iron oxide nanoparticles (SPIONs on granulosa cells, which are very important for ovarian function and female fertility. Human granulosa cells (HLG-5 were treated with SPIONs, either coated with lauric acid (SEONLA only, or additionally with a protein corona of bovine serum albumin (BSA; SEONLA-BSA, or with dextran (SEONDEX. Both micronuclei testing and the detection of γH2A.X revealed no genotoxic effects of SEONLA-BSA, SEONDEX or SEONLA. Thus, it was demonstrated that different coatings of SPIONs improve biocompatibility, especially in terms of genotoxicity towards cells of the reproductive system.

  5. Plant genotoxicity: a molecular cytogenetic approach in plant bioassays.

    Science.gov (United States)

    Maluszynska, Jolanta; Juchimiuk, Jolanta

    2005-06-01

    It is important for the prevention of DNA changes caused by environment to understand the biological consequences of DNA damages and their molecular modes of action that lead to repair or alterations of the genetic material. Numerous genotoxicity assay systems have been developed to identify DNA reactive compounds. The available data show that plant bioassays are important tests in the detection of genotoxic contamination in the environment and the establishment of controlling systems. Plant system can detect a wide range of genetic damage, including gene mutations and chromosome aberrations. Recently introduced molecular cytogenetic methods allow analysis of genotoxicity, both at the chromosomal and DNA level. FISH gives a new possibility of the detection and analysis of chromosomal rearrangements in a great detail. DNA fragmentation can be estimated using the TUNEL test and the single cell gel electrophoresis (Comet assay).

  6. Mequindox Induced Genotoxicity and Carcinogenicity in Mice

    Directory of Open Access Journals (Sweden)

    Qianying Liu

    2018-04-01

    Full Text Available Mequindox (MEQ, acting as an inhibitor of deoxyribonucleic acid (DNA synthesis, is a synthetic heterocyclic N-oxides. To investigate the potential carcinogenicity of MEQ, four groups of Kun-Ming (KM mice (50 mice/sex/group were fed with diets containing MEQ (0, 25, 55, and 110 mg/kg for one and a half years. The result showed adverse effects on body weights, feed consumption, hematology, serum chemistry, organ weights, relative organ weights, and incidence of tumors during most of the study period. Treatment-related changes in hematology, serum chemistry, relative weights and histopathological examinations revealed that the hematological system, liver, kidneys, and adrenal glands, as well as the developmental and reproductive system, were the main targets after MEQ administration. Additionally, MEQ significantly increased the frequency of micronucleated normochromatic erythrocytes in bone marrow cells of mice. Furthermore, MEQ increased the incidence of tumors, including mammary fibroadenoma, breast cancer, corticosuprarenaloma, haemangiomas, hepatocarcinoma, and pulmonary adenoma. Interestingly, the higher incidence of tumors was noted in M25 mg/kg group, the lowest dietary concentration tested, which was equivalent to approximately 2.25 and 1.72 mg/kg b.w./day in females and males, respectively. It was assumed that the lower toxicity might be a reason for its higher tumor incidence in M25 mg/kg group. This finding suggests a potential relationships among the dose, general toxicity and carcinogenicity in vivo, and further study is required to reveal this relationship. In conclusion, the present study demonstrates that MEQ is a genotoxic carcinogen in KM mice.

  7. Hepatotoxicity and genotoxicity of gasoline fumes in albino rats

    Directory of Open Access Journals (Sweden)

    Folarin O. Owagboriaye

    2017-09-01

    Full Text Available Toxic effects of gasoline fumes have been reported, but evidence of its hepatotoxicity and genotoxicity are rare. Therefore, this study assesses hepatotoxicity and genotoxicity of gasoline fumes on forty Albino rats randomly assigned to five experimental treatments (T with eight rats per treatment (T1, T2, T3, T4 and T5. T1(Control was housed in a section of experimental animal house free from gasoline fumes while T2, T3, T4 and T5 were exposed to gasoline fumes in exposure chambers for one, three, five and nine hours daily respectively for twelve weeks. Serum alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP and histopathological examination of the liver tissues were used as diagnostic markers to assess liver dysfunction. Genotoxicity test was conducted on the lung tissues using randomly amplified polymorphic DNA fingerprinting polymerase chain reaction (RAPD PCR technique. Significant increase (p < 0.05 in the level of ALT, AST and ALP for T2, T3, T4 and T5 compared to T1 were recorded. Photomicrograph examination of the liver sections of T1 showed hepatic tissue with normal liver cell architecture while that of T2, T3, T4 and T5 revealed degenerative changes in the ultrastructural integrity of the hepatic cells. Genotoxicity test revealed DNA bands at a reducing intensity from T1 to T5. Dendrogram showed DNA damage in the lungs of T3, T4 and T5 were closely similar and the genotoxic impact was more in T3. Frequent exposure to gasoline fumes was observed to induce hepatoxicity and genotoxicity, hence impairing the normal liver function and gene structure.

  8. Subtle cytotoxicity and genotoxicity differences in superparamagnetic iron oxide nanoparticles coated with various functional groups

    Directory of Open Access Journals (Sweden)

    Hong SC

    2011-12-01

    , and DNA stability in L-929 fibroblasts were determined by water-soluble tetrazolium, 2',7'-dichlorodihydrofluorescein, lactate dehydrogenase, and comet assays, respectively. Our toxicological observations suggest that the functional groups and sizes of SPIONs are critical determinants of cellular responses, degrees of cytotoxicity and genotoxicity, and potential mechanisms of toxicity. Nanoparticles with various surface modifications and of different sizes induced slight, but possibly meaningful, changes in cell cytotoxicity and genotoxicity, which would be significantly valuable in further studies of bioconjugation and cell interaction for drug delivery, cell culture, and cancer-targeting applications.Keywords: superparamagnetic iron oxide nanoparticles, surface functional groups, cytotoxicity, genotoxicity

  9. Fusion facility siting considerations

    International Nuclear Information System (INIS)

    Bussell, G.T.

    1985-01-01

    Inherent in the fusion program's transition from hydrogen devices to commercial power machines is a general increase in the size and scope of succeeding projects. This growth will lead to increased emphasis on safety, environmental impact, and the external effects of fusion in general, and of each new device in particular. A critically important consideration in this regard is site selection. The purpose of this paper is to examine major siting issues that may affect the economics, safety, and environmental impact of fusion

  10. The Consultancy Activity on In Silico Models for Genotoxic Prediction of Pharmaceutical Impurities.

    Science.gov (United States)

    Pavan, Manuela; Kovarich, Simona; Bassan, Arianna; Broccardo, Lorenza; Yang, Chihae; Fioravanzo, Elena

    2016-01-01

    The toxicological assessment of DNA-reactive/mutagenic or clastogenic impurities plays an important role in the regulatory process for pharmaceuticals; in this context, in silico structure-based approaches are applied as primary tools for the evaluation of the mutagenic potential of the drug impurities. The general recommendations regarding such use of in silico methods are provided in the recent ICH M7 guideline stating that computational (in silico) toxicology assessment should be performed using two (Q)SAR prediction methodologies complementing each other: a statistical-based method and an expert rule-based method.Based on our consultant experience, we describe here a framework for in silico assessment of mutagenic potential of drug impurities. Two main applications of in silico methods are presented: (1) support and optimization of drug synthesis processes by providing early indication of potential genotoxic impurities and (2) regulatory evaluation of genotoxic potential of impurities in compliance with the ICH M7 guideline. Some critical case studies are also discussed.

  11. Correlation between the genotoxicity endpoints measured by two different genotoxicity assays: comet assay and CBMN assay

    Directory of Open Access Journals (Sweden)

    Carina Ladeira

    2015-06-01

    The results concerning of positive findings by micronuclei and non significant ones by comet assay, are corroborated by Deng et al. (2005 study performed in workers occupationally exposed to methotrexate, also a cytostatic drug. According to Cavallo et al. (2009, the comet assay seems to be more suitable for the prompt evaluation of the genotoxic effects, for instance, of polycyclic aromatic hydrocarbons mixtures containing volatile substances, whereas the micronucleus test seems more appropriate to evaluate the effects of exposure to antineoplastic agents. However, there are studies that observed an increase in both the comet assay and the micronucleus test in nurses handling antineoplastic drugs, although statistical significance was only seen in the comet assay, quite the opposite of our results (Maluf & Erdtmann, 2000; Laffon et al. 2005.

  12. In-vitro Antioxidant, Cytotoxic, Cholinesterase Inhibitory Activities and Anti-Genotoxic Effects of Hypericum retusum Aucher Flowers, Fruits and Seeds Methanol Extracts in Human Mononuclear Leukocytes.

    Science.gov (United States)

    Keskin, Cumali; Aktepe, Necmettin; Yükselten, Yunus; Sunguroglu, Asuman; Boğa, Mehmet

    2017-01-01

    The present study investigates the antioxidant, anticancer, anticholinesterase, anti-genotoxic activities and phenolic contents of flower, fruit and seed methanol extracts of Hypericum retusum AUCHER. The amounts of protocatechuic acid, catechin, caffeic acid and syringic acid in methanol extracts were determined by HPLC. Total phenolic content of H. retusum seed extract was found more than fruit and flower extracts. The DPPH free radical scavenging activity of flower and seed methanol extracts showed close activity versus BHT as control. Among three extracts of H. retusum only flower methanol extract was exhibited considerable cytotoxic activities against to HeLa and NRK-52E cell lines. Moreover, seed methanol extract showed both acetyl and butyrl-cholinesterase inhibitory activity. The highest anti-genotoxic effects were seen 25 and 50 μg/mL concentrations. In this study, the extracts showed a strong antioxidant and anti-genotoxic effect. The seed extract was more efficient- than extracts of fruit and flowers. Our results suggest that the antioxidant and anti-genotoxic effects of extracts depend on their phenolic contents. Further studies should evaluate the in-vitro and in-vivo the benefits of H. retusum seed methanol extracts.

  13. SIGNALING TO THE P53 TUMOR SUPPRESSOR THROUGH PATHWAYS ACTIVATED BY GENOTOXIC AND NON-GENOTOXIC STRESSES.

    Energy Technology Data Exchange (ETDEWEB)

    ANDERSON,C.W.APPELLA,E.

    2002-07-01

    The p53 tumor suppressor is a tetrameric transcription factor that is post-translational modified at {approx}18 different sites by phosphorylation, acetylation, or sumoylation in response to various cellular stress conditions. Specific posttranslational modifications, or groups of modifications, that result from the activation of different stress-induced signaling pathways are thought to modulate p53 activity to regulate cell fate by inducing cell cycle arrest, apoptosis, or cellular senescence. Here we review the posttranslational modifications to p53 and the pathways that produce them in response to both genotoxic and non-genotoxic stresses.

  14. Cytotoxicity and genotoxicity of lipid nanocapsules.

    Science.gov (United States)

    Le Roux, Gaël; Moche, Hélène; Nieto, Alejandro; Benoit, Jean-Pierre; Nesslany, Fabrice; Lagarce, Frédéric

    2017-06-01

    Lipid nanocapsules (LNCs) offer a promising method for the entrapment and nanovectorisation of lipophilic molecules. This new type of nanocarrier, formulated according to a solvent-free process and using only regulatory-approved components, exhibits many prerequisites for being well tolerated. Although toxicological reference values have already been obtained in mice, interaction of LNCs at the cell level needs to be elucidated. LNCs, measuring from 27.0±0.1nm (25nm LNCs) and 112.1±1.8nm (100nm LNCs) and with a zeta potential between -38.7±1.2mV and +9.18±0.4mV, were obtained by a phase inversion process followed by post-insertion of carboxy- or amino-DSPE-PEG. Trypan blue, MTS and neutral red uptake (NRU) assays were performed to evaluate the cytotoxicity of LNCs on mouse macrophage-like cells RAW264.7 after 24h of exposure. The determination of 50% lethal concentration (LC50) showed a size effect of LNCs on toxicity profiles: LC50 ranged from 1.036mg/L (MTS) and 0.477mg/mL (NRU) for 25nm LNCs, to 4.42mg/mL (MTS) and 2.18mg/mL (NRU) for 100nm LNCs. Surfactant Solutol® HS15 has been shown to be the only constituent to exhibit cytotoxicity; its LC50 reached 0.427mg/mL. Moreover, LNCs were not more toxic than their components in simple mixtures. At sublethal concentration, 100nm LNCs only were able to induce a significant production of nitric oxide (NO) by RAW264.7 cells, as assessed by the Griess reaction. Again, surfactant was the only component responsible for an increased NO release (1.8±0.2-fold). Genotoxicity assays revealed no DNA damage on human lymphocytes in both the in vitro Comet and micronucleus assays using 4-hour and 24-hour treatments, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Genotoxic Maillard byproducts in current phytopharmaceutical preparations of Echinodorus grandiflorus

    Directory of Open Access Journals (Sweden)

    ELISANGELA C. LIMA-DELLAMORA

    2014-09-01

    Full Text Available Extracts of Echinodorus grandiflorus obtained from dried leaves by three different techniques were evaluated by bacterial lysogenic induction assay (Inductest in relation to their genotoxic properties. Before being added to test cultures, extracts were sterilized either by steam sterilization or ultraviolet light. Only the extracts prepared by infusion and steam sterilized have shown genotoxic activity. The phytochemical analysis revealed the presence of the flavonoids isovitexin, isoorientin, swertisin and swertiajaponin, isolated from a genotoxic fraction. They were assayed separately and tested negative in the Inductest protocol. The development of browning color and sweet smell in extracts submitted to heat, prompted further chemical analysis in search for Maillard's reaction precursors. Several aminoacids and reducing sugars were cast in the extract. The presence of characteristic Maillard's melanoidins products was determined by spectrophotometry in the visible region and the inhibition of this reaction was observed when its characteristic inhibitor, sodium bisulfite, was added prior to heating. Remarkably, this is the first paper reporting on the appearance of such compounds in a phytomedicine preparation under a current phytopharmaceutical procedure. The genotoxic activity of such heat-prepared infusions imply in some risk of developing degenerative diseases for patients in long-term, uncontrolled use of such phytomedicines.

  16. Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water

    Science.gov (United States)

    Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroaceticacid and chlorite) are not carcinogenic-in either of2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxicity...

  17. Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water**

    Science.gov (United States)

    Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroaceticacid and chlorite) are not carcinogenic-in either of2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxicity...

  18. Mutagenicity and genotoxicity of coal fly ash water leachate.

    Science.gov (United States)

    Chakraborty, Rajarshi; Mukherjee, Anita

    2009-03-01

    Fly ash is a by-product of coal-fired electricity generation plants. The prevalent practice of disposal is as slurry of ash and water to storage or ash ponds located near power stations. This has lain to waste thousands of hectares of land all over the world. Since leaching is often the cause of off-site contamination and pathway of introduction into the human environment, a study on the genotoxic effects of fly ash leachate is essential. Leachate prepared from the fly ash sample was analyzed for metal content, and tested for mutagenicity and genotoxicity. Analyses of metals show predominance of the metals-sodium, silicon, potassium, calcium, magnesium, iron, manganese, zinc, and sulphate. The Ames Salmonella mutagenicity assay, a short-term bacterial reverse mutation assay, was conducted on two-tester strains of Salmonella typhimurium strains TA97a and TA102. For genotoxicity, the alkaline version of comet assay on fly ash leachate was carried in vitro on human blood cells and in vivo on Nicotiana plants. The leachate was directly mutagenic and induced significant (Ppercentage (%), tail length (mum), and olive tail moment (arbitrary units). Our results indicate that leachate from fly ash dumpsites has the genotoxic potential and may lead to adverse effects on vegetation and on the health of exposed human populations.

  19. Formation and removal of genotoxic activity during UV/H

    NARCIS (Netherlands)

    Heringa, M.B.; Harmsen, D.J.H.; Beerendonk, E.F.; Reus, A.A.; Krul, C.A.M.; Metz, D.H.; Ijpelaar, G.F.

    2011-01-01

    The objective of this study was to determine the genotoxic activity of water after UV/H2O2 oxidation and GAC filtration. Pre-treated surface water from three locations was treated with UV/H2O2 with medium pressure (MP) lamps and passed through granulated

  20. Mercury-induced genotoxicity in marine diatom (Chaetoceros tenuissimus)

    Digital Repository Service at National Institute of Oceanography (India)

    Sarker, S.; Desai, S.R.; Verlecar, X.N.; Sarker, M.S.; Sarkar, A.

    In this paper, we present an evaluation of genotoxic responses in marine diatom, Chaetoceros tenuissimus, isolated from Kandla Creek (lat 23.03° N, long 70.22° E), Gujarat, India, in terms of impairment of DNA integrity as a function...

  1. Genotoxicity and mutagenicity of solid waste leachates: A review

    African Journals Online (AJOL)

    user

    2013-07-03

    Jul 3, 2013 ... There is need for a shift from waste disposal to sustainable waste management. Awareness on possible health ... Key words: Solid waste leachate, genotoxicity, mutagenicity, environmental pollution. INTRODUCTION. Solid wastes .... landfills and incineration residues from Japan include persistent organic ...

  2. Genotoxic damage in cultured human peripheral blood lymphocytes ...

    African Journals Online (AJOL)

    Falaq Naz

    2012-06-29

    Jun 29, 2012 ... Genotoxic damage in cultured human peripheral blood lymphocytes of oral ... catechol estrogens and quinines, via redox reactions causes oxidative damage to .... volume was prepared for each donor. About, 0.8 ml of cell sus .... duce the adverse effects of OCs, such as the reduction in the estrogen content.

  3. QSAR ligand dataset for modelling mutagenicity, genotoxicity, and rodent carcinogenicity

    Directory of Open Access Journals (Sweden)

    Davy Guan

    2018-04-01

    Full Text Available Five datasets were constructed from ligand and bioassay result data from the literature. These datasets include bioassay results from the Ames mutagenicity assay, Greenscreen GADD-45a-GFP assay, Syrian Hamster Embryo (SHE assay, and 2 year rat carcinogenicity assay results. These datasets provide information about chemical mutagenicity, genotoxicity and carcinogenicity.

  4. Does Caesalpinia bonducella ameliorate genotoxicity? An in vitro ...

    African Journals Online (AJOL)

    The aim of the study is to investigate the antimutagenic and antigenotoxic potential of alcoholic extracts of C. bonducella against methyl methane sulfonate (MMS) induced genotoxicity. In this experiment we have used in vitro method i.e., human lymphocyte culture and in vivo method in bone marrow cells of albino mice, ...

  5. Evaluation of Genotoxic Pressure along the Sava River.

    Directory of Open Access Journals (Sweden)

    Stoimir Kolarević

    Full Text Available In this study we have performed a comprehensive genotoxicological survey along the 900 rkm of the Sava River. In total, 12 sites were chosen in compliance with the goals of GLOBAQUA project dealing with the effects of multiple stressors on biodiversity and functioning of aquatic ecosystems. The genotoxic potential was assessed using a complex battery of bioassays performed in prokaryotes and aquatic eukaryotes (freshwater fish. Battery comprised evaluation of mutagenicity by SOS/umuC test in Salmonella typhimurium TA1535/pSK1002. The level of DNA damage as a biomarker of exposure (comet assay and biomarker of effect (micronucleus assay and the level of oxidative stress as well (Fpg-modified comet assay was studied in blood cells of bleak and spirlin (Alburnus alburnus/Alburnoides bipunctatus respectively. Result indicated differential sensitivity of applied bioassays in detection of genotoxic pressure. The standard and Fpg-modified comet assay showed higher potential in differentiation of the sites based on genotoxic potential in comparison with micronucleus assay and SOS/umuC test. Our data represent snapshot of the current status of the river which indicates the presence of genotoxic potential along the river which can be traced to the deterioration of quality of the Sava River by communal and industrial wastewaters. The major highlight of the study is that we have provided complex set of data obtained from a single source (homogeneity of analyses for all samples.

  6. Genotoxicity evaluation of the insecticide ethion in root of Allium ...

    African Journals Online (AJOL)

    In this study, the genotoxic effects of ethion were investigated in the mitotic cell division of Allium cepa. Primary roots of A. cepa were treated with various concentrations (25, 50, 75, and 100%) of ethion solutions for different duration of time. The result revealed that increase in the concentration and duration of treatment ...

  7. Somatic cell genotoxicity at the glycophorin A locus in humans

    International Nuclear Information System (INIS)

    Jensen, R.H.; Grant, S.G.; Langlois, R.G.; Bigbee, W.L.

    1990-01-01

    We have developed an assay for detecting variant erythrocytes that occur as a result of in vivo allele loss at the glycophorin A (GPA) locus on chromosome 4 in humans. This gene codes for an erythroid- specific cell surface glycoprotein, and with our assay we are able to detect rare variant erythrocytes that have lost expression of one of the two GPA alleles. Two distinctly different variant cell types are detected with this assay. One variant cell type (called N OE) is hemizygous. Our assay also detects homozygous variant erythrocytes that have lost expression of the GPA(M) allele and express the GPA(N) allele at twice the heterozygous level. The results of this assay are an enumeration of the frequency of N OE and NN variant cell types for each individual analyzed. These variant cell frequencies provide a measure of the amount of somatic cell genotoxicity that has occurred at the GPA locus. Such genotoxicity could be the result of (1) reactions of toxic chemicals to which the individual has been exposed, or (2) high energy radiation effects on erythroid precursor cells, or (3) errors in DNA replication or repair in these cells of the bone marrow. Thus, the GPA-based variant cell frequency can serve as a biodosimeter that indicates the amount of genotoxic exposure each individual has received. Because two very different kinds of variant cells are enumerated, different kinds of genotoxicity should be distinguishable. Results of the GPA somatic genotoxicity assay may also provide valuable information for cancer-risk estimation on each individual. 16 refs

  8. Assessing the risks of genotoxicity in the therapeutic development of induced pluripotent stem cells.

    Science.gov (United States)

    Hong, So Gun; Dunbar, Cynthia E; Winkler, Thomas

    2013-02-01

    Induced pluripotent stem cells (iPSCs) have great potential for regenerative medicine as well as for basic and translational research. However, following the initial excitement over the enormous prospects of this technology, several reports uncovered serious concerns regarding its safety for clinical applications and reproducibility for laboratory applications such as disease modeling or drug screening. In particular, the genomic integrity of iPSCs is the focus of extensive research. Epigenetic remodeling, aberrant expression of reprogramming factors, clonal selection, and prolonged in vitro culture are potential pathways for acquiring genomic alterations. In this review, we will critically discuss current reprogramming technologies particularly in the context of genotoxicity, and the consequences of these alternations for the potential applications of reprogrammed cells. In addition, current strategies of genetic modification of iPSCs, as well as applicable suicide strategies to control the risk of iPSC-based therapies will be introduced.

  9. Genotoxic damage in non-irradiated cells: contribution from the bystander effect

    International Nuclear Information System (INIS)

    Zhou, H.; Randers-Pherson, G.; Suzuki, M.; Waldren, C.A.; Hei, T.K.

    2002-01-01

    It has always been accepted dogma that the deleterious effects of ionising radiation such as mutagenesis and carcinogenesis are due mainly to direct damage to DNA. Using the Columbia University charged-particle microbeam and the highly sensitive A L cell mutagenic assay, it is shown here that non-irradiated cells acquire the mutagenic phenotype through direct contact with cells whose nuclei are traversed with 2 alpha particles each. Pre-treatment of cells with lindane, a gap junction inhibitor, significantly decreased the mutant yield. Furthermore, when irradiated cells were mixed with control cells in a similar ration as the in situ studies, no enhancement in bystander mutagenesis was detected. Our studies provide clear evidence that genotoxic damage can be induced in non-irradiated cells, and that gap junction mediated cell-cell communication plays a critical role in the bystander phenomenon. (author)

  10. Molecular and genotoxic effects in Mytilus galloprovincialis exposed to tritiated water at an elevated temperature

    Energy Technology Data Exchange (ETDEWEB)

    Dallas, L.; Jha, A. [School of Biological Sciences, Plymouth University (United Kingdom); Bean, T.; Lyons, B. [Cefas Weymouth Laboratory (United Kingdom); Turner, A. [School of Geography, Earth and Environmental Sciences, Plymouth University (United Kingdom)

    2014-07-01

    Radioactive contaminants do not occur in isolation; organisms are also exposed to fluctuations in biological, biotic and physico-chemical factors, such as competition, other contaminants, salinity and temperature. Thermal discharge from nuclear facilities is considered to be one of the most important environmental issues surrounding these establishments, second only to the release of radionuclides. Cooling water from nuclear institutions is one of the major sources of tritium ({sup 3}H) to the aquatic environment; temperature is therefore an abiotic factor of particular concern when it comes to assessing the potential detrimental impacts of {sup 3}H exposure in marine species. In this context, we used a molecular approach to elucidate the potential mechanisms behind the genotoxicity of tritiated water (HTO) to marine mussels, at 'normal' and elevated temperatures. Mussels were exposed to control seawater or 15 MBq L{sup -1} HTO at 15 and 25 deg. C for 7 days, with haemolymph and gill tissue sampling (for comet assay to detect DNA strand breaks and gene expression analysis, respectively) after 0, 1, 12, 72 and 168 h. In addition, a Cu concentration of 40 μg L{sup -1} (previously established as genotoxic under these exposure conditions) was used concurrently as a positive control (at 15 deg. C). Tissue-specific accumulation of {sup 3}H was also determined, allowing the calculation of dose rates using the ERICA tool. Comparison of DNA strand breakage (DSB) as a function of time suggested that significant levels of DSB were induced earlier in haemocytes of mussels exposed to HTO at 25 deg. C compared to 15 deg. C (72 h vs. 168 h). Alterations in transcriptional expression of key genes also suggest that the 72 h time point is critical, with gill showing reduced expression of hsp70, hsp90, mt20, p53 and rad51 during HTO exposure at the elevated temperature. In contrast, HTO exposure at 15 deg. C resulted in significant up-regulation of the same genes after 72

  11. Genotoxicity of diuron and glyphosate in oyster spermatozoa and embryos.

    Science.gov (United States)

    Akcha, F; Spagnol, C; Rouxel, J

    2012-01-15

    We investigated the effects of genotoxicant exposure in gametes and embryos to find a possible link between genotoxicity and reproduction/developmental impairment, and explore the impact of chemical genotoxicity on population dynamics. Our study focused on the genotoxic effects of two herbicides on oyster gametes and embryos: glyphosate (both as an active substance and in the Roundup formulation) and diuron. France is Europe's leading consumer of agrochemical substances and as such, contamination of France's coastal waters by pesticides is a major concern. Glyphosate and diuron are among the most frequently detected herbicides in oyster production areas; as oyster is a specie with external reproduction, its gametes and embryos are in direct contact with the surrounding waters and are hence particularly exposed to these potentially dangerous substances. In the course of this study, differences in genotoxic and embryotoxic responses were observed in the various experiments, possibly due to differences in pollutant sensitivity between the tested genitor lots. Glyphosate and Roundup had no effect on oyster development at the concentrations tested, whereas diuron significantly affected embryo-larval development from the lowest tested concentration of 0.05 μg L⁻¹, i.e. an environmentally realistic concentration. Diuron may therefore have a significant impact on oyster recruitment rates in the natural environment. Our spermiotoxicity study revealed none of the tested herbicides to be cytotoxic for oyster spermatozoa. However, the alkaline comet assay showed diuron to have a significant genotoxic effect on oyster spermatozoa at concentrations of 0.05 μg L⁻¹ upwards. Conversely, no effects due to diuron exposure were observed on sperm mitochondrial function or acrosomal membrane integrity. Although our initial results showed no negative effect on sperm function, the possible impact on fertilization rate and the consequences of the transmission of damaged DNA for

  12. Genotoxicity of 2-bromo-3′-chloropropiophenone

    International Nuclear Information System (INIS)

    Meng, Fanxue; Yan, Jian; Li, Yan; Fu, Peter P.; Fossom, Linda H.; Sood, Ramesh K.; Mans, Daniel J.; Chu, Pei-I; Moore, Martha M.; Chen, Tao

    2013-01-01

    Impurities are present in any drug substance or drug product. They can be process-related impurities that are not completely removed during purification or are formed due to the degradation of the drug substance over the product shelf-life. Unlike the drug substance, impurities generally do not have beneficial effects and may present a risk without associated benefit. Therefore, their amount should be minimized. 2-Bromo-3′-chloropropiophenone (BCP) is an impurity of bupropion, a second-generation antidepressant and a smoking cessation aid. The United States Pharmacopeia recommends an acceptable level for BCP that is not more than 0.1% of the bupropion. Because exposure to genotoxic impurities even at low levels is of significant concern, it is important to determine whether or not BCP is genotoxic. Therefore, in this study the Ames test and the in vitro micronucleus assay were conducted to evaluate the genotoxicity of BCP. BCP was mutagenic with S9 metabolic activation, increasing the mutant frequencies in a concentration-dependent manner, up to 22- and 145-fold induction over the controls in Salmonella strains TA100 and TA1535, respectively. BCP was also positive in the in vitro micronucleus assay, resulting in up to 3.3- and 5.1-fold increase of micronucleus frequency for treatments in the absence and presence of S9, respectively; and 9.9- and 7.4-fold increase of aneuploidies without and with S9, respectively. The addition of N-acetyl-L-cysteine, an antioxidant, reduced the genotoxicity of BCP in both assays. Further studies showed that BCP treatment resulted in induction of reactive oxygen species (ROS) in the TK6 cells. The results suggest that BCP is mutagenic, clastogenic, and aneugenic, and that these activities are mediated via generation of reactive metabolites. - Highlights: • 2-Bromo-3′-chloropropiophenone is an impurity of bupropion. • BCP was positive in both the Ames test and the in vitro micronucleus assay. • It induced high frequencies of

  13. Genotoxicity of 2-bromo-3′-chloropropiophenone

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Fanxue; Yan, Jian; Li, Yan [Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079 (United States); Fu, Peter P. [Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079 (United States); Fossom, Linda H.; Sood, Ramesh K.; Mans, Daniel J.; Chu, Pei-I [Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993 (United States); Moore, Martha M. [Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079 (United States); Chen, Tao, E-mail: tao.chen@fda.hhs.gov [Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079 (United States)

    2013-07-15

    Impurities are present in any drug substance or drug product. They can be process-related impurities that are not completely removed during purification or are formed due to the degradation of the drug substance over the product shelf-life. Unlike the drug substance, impurities generally do not have beneficial effects and may present a risk without associated benefit. Therefore, their amount should be minimized. 2-Bromo-3′-chloropropiophenone (BCP) is an impurity of bupropion, a second-generation antidepressant and a smoking cessation aid. The United States Pharmacopeia recommends an acceptable level for BCP that is not more than 0.1% of the bupropion. Because exposure to genotoxic impurities even at low levels is of significant concern, it is important to determine whether or not BCP is genotoxic. Therefore, in this study the Ames test and the in vitro micronucleus assay were conducted to evaluate the genotoxicity of BCP. BCP was mutagenic with S9 metabolic activation, increasing the mutant frequencies in a concentration-dependent manner, up to 22- and 145-fold induction over the controls in Salmonella strains TA100 and TA1535, respectively. BCP was also positive in the in vitro micronucleus assay, resulting in up to 3.3- and 5.1-fold increase of micronucleus frequency for treatments in the absence and presence of S9, respectively; and 9.9- and 7.4-fold increase of aneuploidies without and with S9, respectively. The addition of N-acetyl-L-cysteine, an antioxidant, reduced the genotoxicity of BCP in both assays. Further studies showed that BCP treatment resulted in induction of reactive oxygen species (ROS) in the TK6 cells. The results suggest that BCP is mutagenic, clastogenic, and aneugenic, and that these activities are mediated via generation of reactive metabolites. - Highlights: • 2-Bromo-3′-chloropropiophenone is an impurity of bupropion. • BCP was positive in both the Ames test and the in vitro micronucleus assay. • It induced high frequencies of

  14. Storage array reflection considerations

    International Nuclear Information System (INIS)

    Haire, M.J.; Jordan, W.C.; Taylor, R.G.

    1997-01-01

    The assumptions used for reflection conditions of single containers are fairly well established and consistently applied throughout the industry in nuclear criticality safety evaluations. Containers are usually considered to be either fully water-reflected (i.e. surrounded by 6 to 12 in. of water) for safety calculations or reflected by 1 in. of water for nominal (structural material and air) conditions. Tables and figures are usually available for performing comparative evaluations of containers under various loading conditions. Reflection considerations used for evaluating the safety of storage arrays of fissile material are not as well established

  15. Study of physiological and genotoxic status of fish populations of Azerbaijan shore of the Caspian sea

    International Nuclear Information System (INIS)

    Kasimov, R.Yu.; Palatnikov, G.M.; Mekhtiev, A.A.

    2005-01-01

    Full text : According to the studies conducted on Ecotox program of Caspian Ecological program, littoral waters of Azerbaijan and Iran are characterized with high content of heavy metals and organic compounds. Actually, all these substances are not just toxicants but mutagens as well. Taking into account these considerations, it appears important to be aware of physiological and genotoxic status of fish populations dwelling along Azerbaijan shore of the Caspian Sea for present time. The purpose of proposed project is collecting data concerning actual physiological and genotoxic status of fish populations dwelling in the littoral zone of Azerbaijan shore of the Caspian Sea. That will present the real picture of ecological status of ichtyofauna in Azerbaijan sector of the Caspian Sea and give grounds to conduct comparative analysis of changes while conducting all kinds of activities in the sea with the data provided within this project's frames. For this purpose we offer to conduct studies of fish populations along Azerbaijan littoral zone of the Caspian Sea beginning from north ones, sharing all shore into 5-6 points where fish catches should be done. Not less than 5 specimens of attached-dwelling fish, for instance gobies, are planned to catch in each of defined points. Blood samples for genotoxic analysis and samples of muscles, livers and gills for immunochemical and histopathological analysis will be taken. Along with this in these points the analysis of water - oxygen content, ph, salinity, temperature will be realized. Physiological status of fish will be evaluated by determination of serotonin-modulating protein content in ELISA-test. This analysis gives precise estimation of serotonergic system status that is very sensitive to adverse conditions. The second test - histopathological tissue studies gives grounds to determine functional status of internal organs of caught fish. The third test - micronuclei counting in erythrocytes. This technique allows

  16. Genotoxicity of topoisomerase II inhibitors: An anti-infective perspective

    International Nuclear Information System (INIS)

    Smart, Daniel J.

    2008-01-01

    At present, an inevitable consequence of a chemical's inhibitory activity on key regulators of DNA topology in bacteria, the type II topoisomerases, is a less pronounced effect on their eukaryotic counterparts. In the context of anti-infectives drug development, this may pose a risk to patient safety as inhibition of eukaryotic type II topoisomerases (TOPO II) can result in the generation of DNA double-strand breaks (DSBs), which have the potential to manifest as mutations, chromosome breakage or cell death. The biological effects of several TOPO II inhibitors in mammalian cells are described herein; their modulation of DSB damage response parameters is examined and evidence for the existence of a threshold concept for genotoxicity and its relevance in safety assessment is discussed. The potential utility of γH2AX, a promising and highly sensitive molecular marker for DSBs, in a novel genotoxicity 'pre-screen' to conventional assays is also highlighted

  17. Genotoxicity of indium tin oxide by comet test

    Directory of Open Access Journals (Sweden)

    İbrahim Hakkı Ciğerci

    2015-06-01

    Full Text Available Indium tin oxide (ITO is used for liquid crystal display (LCDs, electrochromic displays, flat panel displays, field emission displays, touch or laptop computer screens, cell phones, energy conserving architectural windows, defogging aircraft and automobile windows, heat-reflecting coatings to increase light bulb efficiency, gas sensors, antistatic window coatings, wear resistant layers on glass, nanowires and nanorods because of its unique properties of high electrical conductivity, transparency and mechanical resistance.Genotoxic effects of ITO were investigated on the root cells of Allium cepa by Comet assay. A. cepa roots were treated with the aqueous dispersions of ITO at 5 different concentrations (12.5, 25, 50, 75, and 100 ppm for 4 h. A significant increase in DNA damage was a observed at all concentrations of ITO by Comet assay. These result indicate that ITO exhibit genotoxic activity in A. cepa root meristematic cells.

  18. Genotoxicity of unmodified and organo-modified montmorillonite

    DEFF Research Database (Denmark)

    Sharma, Anoop Kumar; Schmidt, Bjørn; Frandsen, Henrik Lauritz

    2010-01-01

    absent in the filtered samples, which was independently confirmed by dynamic light-scattering measurements. Detection and identification of free quaternary ammonium modifier in the filtered sample was carried out by HPLC-Q-TOF/MS and revealed a total concentration of a mixture of quaternary ammonium...... assay, none of the clays produced ROS in a cell-free test system (the DCFH-DA assay). Inductively coupled plasma mass-spectrometry (ICP-MS) was used to detect clay particles in the filtered samples using aluminium as a tracer element characteristic to clay. The results indicated that clay particles were...... analogues of 1.57 mu g/ml. These findings suggest that the genotoxicity of organo-modified montmorillonite was caused by the organo-modifier. The detected organo-modifier mixture was synthesized and comet-assay results showed that the genotoxic potency of this synthesized organo-modifier was in the same...

  19. Genotoxicity of gemfibrozil in the gilthead seabream (Sparus aurata).

    Science.gov (United States)

    Barreto, A; Luis, L G; Soares, A M V M; Paíga, P; Santos, L H M L M; Delerue-Matos, C; Hylland, K; Loureiro, S; Oliveira, M

    2017-09-01

    Widespread use of pharmaceuticals and suboptimal wastewater treatment have led to increased levels of these substances in aquatic ecosystems. Lipid-lowering drugs such as gemfibrozil, which are among the most abundant human pharmaceuticals in the environment, may have deleterious effects on aquatic organisms. We examined the genotoxicity of gemfibrozil in a fish species, the gilthead seabream (Sparus aurata), which is commercially important in southern Europe. Following 96-h waterborne exposure, molecular (erythrocyte DNA strand breaks) and cytogenetic (micronuclei and other nuclear abnormalities in cells) endpoints were measured. Gemfibrozil was positive in both endpoints, at environmentally relevant concentrations, a result that raises concerns about the potential genotoxic effects of the drug in recipient waters. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. DNA Dosimetry Assessment for Sunscreen Genotoxic Photoprotection

    OpenAIRE

    Schuch, André Passaglia; Lago, Juliana Carvalhães; Yagura, Teiti; Menck, Carlos Frederico Martins

    2012-01-01

    Background: Due to the increase of solar ultraviolet radiation (UV) incidence over the last few decades, the use of sunscreen has been widely adopted for skin protection. However, considering the high efficiency of sunlight-induced DNA lesions, it is critical to improve upon the current approaches that are used to evaluate protection factors. An alternative approach to evaluate the photoprotection provided by sunscreens against daily UV radiation-induced DNA damage is provided by the systemat...

  1. Genotoxicity of extracts of Japanese traditional herbal medicines (Kampo)

    OpenAIRE

    Makoto, Katami; Haruo, Kuboniwa; Shunichi, Maemura; Toshihiko, Yanagisawa; New Drug Discovery Laboratory, R & D Division, TSUMURA & Co.; New Drug Discovery Laboratory, R & D Division, TSUMURA & Co.; New Drug Discovery Laboratory, R & D Division, TSUMURA & Co.; New Drug Discovery Laboratory, R & D Division, TSUMURA & Co.

    2002-01-01

    The possible genotoxicity potential of 128 Japanese traditional herbal medicines (Kampo) was investigated using a bacterial reverse mutation test (the Ames test), an in vivo micronucleus test (MN test) in mouse bone marrow cells and an unscheduled DNA synthesis test (UDS test) in rat hepatocytes. Of 128 Kampo extracts examined, 98 did not induce mutations in bacteria while 30 induced mutations weakly in Salmonella typhimurium TA1537. Extracts of Scutellariae Radix, a common herbal drug, and i...

  2. Bioengineering a non-genotoxic vector for genetic modification of mesenchymal stem cells.

    Science.gov (United States)

    Chen, Xuguang; Nomani, Alireza; Patel, Niket; Nouri, Faranak S; Hatefi, Arash

    2018-01-01

    Vectors used for stem cell transfection must be non-genotoxic, in addition to possessing high efficiency, because they could potentially transform normal stem cells into cancer-initiating cells. The objective of this research was to bioengineer an efficient vector that can be used for genetic modification of stem cells without any negative somatic or genetic impact. Two types of multifunctional vectors, namely targeted and non-targeted were genetically engineered and purified from E. coli. The targeted vectors were designed to enter stem cells via overexpressed receptors. The non-targeted vectors were equipped with MPG and Pep1 cell penetrating peptides. A series of commercial synthetic non-viral vectors and an adenoviral vector were used as controls. All vectors were evaluated for their efficiency and impact on metabolic activity, cell membrane integrity, chromosomal aberrations (micronuclei formation), gene dysregulation, and differentiation ability of stem cells. The results of this study showed that the bioengineered vector utilizing VEGFR-1 receptors for cellular entry could transfect mesenchymal stem cells with high efficiency without inducing genotoxicity, negative impact on gene function, or ability to differentiate. Overall, the vectors that utilized receptors as ports for cellular entry (viral and non-viral) showed considerably better somato- and genosafety profiles in comparison to those that entered through electrostatic interaction with cellular membrane. The genetically engineered vector in this study demonstrated that it can be safely and efficiently used to genetically modify stem cells with potential applications in tissue engineering and cancer therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Evaluation of river water genotoxicity using the piscine micronucleus test.

    Science.gov (United States)

    Ergene, Serap; Cavaş, Tolga; Celik, Ayla; Köleli, Nurcan; Aymak, Cemil

    2007-07-01

    The Berdan River, which empties into the Mediterranean Sea on the east coast of Turkey, receives discharges of industrial and municipal waste. In the present study, the in vivo piscine micronucleus (MN) test was used to evaluate the genotoxicity of water samples collected from different locations along the Berdan River. Nile tilapia (Oreochromis niloticus) were exposed in the laboratory for 2, 4, and 6 days, and micronuclei were evaluated in peripheral blood erythrocytes, gill cells, and caudal fin epithelial cells. A single dose of 5 mg/L cyclophosphamide was used as a positive control. In addition to micronuclei, nuclear abnormalities (NAs), such as binucleated cells and blebbed, notched, and lobed nuclei, were assessed in the erythrocytes, and chemical analyses were carried out to determine the amount of heavy metals in the water samples. MN and NA frequencies were significantly elevated (up to 2- to 3-fold) in fish exposed to river water samples taken downstream of potential discharges, and the elevated responses in gill and fin cells were related to the concentration of heavy metals in the water. MN frequencies (expressed as micronucleated cells/1,000 cells), in both treated and untreated fish, were greatest in gill cells (range: 0.80-3.70), and generally lower in erythrocytes (range: 0.50-2.80), and fin cells (range: 0.45-1.70). The results of this study indicate that the Berdan River is contaminated with genotoxic pollutants and that the genotoxicity is related to the discharge of wastes into the river water.

  4. Genotoxic evaluation of terbinafine in human lymphocytes in vitro.

    Science.gov (United States)

    Tolomeotti, Danielle; de Castro-Prado, Marialba Avezum Alves; de Sant'Anna, Juliane Rocha; Martins, Ana Beatriz Tozzo; Della-Rosa, Valter Augusto

    2015-01-01

    Terbinafine is an antimycotic drug usually used against several superficial fungal infections and with a potential application in the treatment of human cancers. Since to date there are few data on the genotoxic effects of terbinafine in mammalian cells, current study evaluated the potential genotoxic of such antifungal agent in cultured human peripheral blood lymphocytes. Terbinafine was used at the peak plasma concentration (1.0 μg/ml) and in four additional concentrations higher than the human plasmatic peak (5.0 μg/ml, 25.0 μg/ml, 50.0 μg/ml and 100.0 μg/ml). Chromosomal aberrations (CA), sister chromatid exchanges (SCE), micronuclei (MN), nucleoplasmic bridges (NP) and nuclear buds (NB) were scored as genetic endpoints. In all analysis no significant differences (α = 0.05, Kruskal-Wallis test) were observed. Complementary criterion adopted to obtain the final response in cytogenetic agreed with statistical results. Therefore, results of this study showed that terbinafine neither induced CA, SCE, MN, NP and NB nor affected significantly mitotic, replication and cytokinesis-block proliferation indices in any of the tested concentrations. It may be assumed that terbinafine was not genotoxic or cytotoxic to cultured human peripheral blood lymphocytes in our experimental conditions.

  5. Genotoxic and apoptotic effects of Goeckerman therapy for psoriasis

    Energy Technology Data Exchange (ETDEWEB)

    Borska, L.; Andrys, C.; Krejsek, J.; Hamakova, K.; Kremlacek, J.; Palicka, V.; Ranna, D.; Fiala, Z. [Charles University Prague, Prague (Czech Republic). Faculty of Medicine

    2010-03-15

    Goeckerman therapy (GT) for psoriasis is based on cutaneous application of crude coal tar (polycyclic aromatic hydrocarbons (PAH)) and exposure to ultraviolet radiation (UVR). PAH and UVR are mutagenic, carcinogenic and immunotoxic agents that promote apoptosis. We evaluated dermal absorption of PAH as well as the genotoxic and apoptotic effects of GT in 20 patients with psoriasis, by determining numbers of chromosomal abnormalities in peripheral lymphocytes, and levels of 1-hydroxypyrene (1-OHP), p53 protein and soluble FasL (sFasL) in urine and/or blood, before and after GT. Psoriasis Area and Severity Index (PASI) score was used to evaluate clinical efficacy of GT. Compared with pre-treatment levels, there was a significant increase in urine 1-OHP, indicating a high degree of dermal absorption of PAH (P <0.01). We also found a significant increase in the number of chromosomal abnormalities in peripheral blood lymphocytes (P <0.001), suggesting that GT is genotoxic; significantly increased p53 protein in plasma (P <0.05), an indicator of cell response to DNA damage; and significantly increased sFasL in serum (P <0.01), an indicator of apoptosis. The PASI score was significantly decreased after GT (P <0.001), confirming clinical benefit of this treatment. Our results demonstrate high dermal absorption of PAH during GT and provide evidence that GT promotes genotoxicity and apoptosis.

  6. Genotoxicity assessment of some cosmetic and food additives.

    Science.gov (United States)

    Di Sotto, Antonella; Maffei, Francesca; Hrelia, Patrizia; Di Giacomo, Silvia; Pagano, Ester; Borrelli, Francesca; Mazzanti, Gabriela

    2014-02-01

    α-Hexylcinnamaldehyde (HCA) and p-tert-butyl-alpha-methylhydrocinnamic aldehyde (BMHCA) are synthetic aldehydes, characterized by a typical floral scent, which makes them suitable to be used as fragrances in personal care (perfumes, creams, shampoos, etc.) and household products, and as flavouring additives in food and pharmaceutical industry. The aldehydic structure suggests the need for a safety assessment for these compounds. Here, HCA and BMHCA were evaluated for their potential genotoxic risk, both at gene level (frameshift or base-substitution mutations) by the bacterial reverse mutation assay (Ames test), and at chromosomal level (clastogenicity and aneuploidy) by the micronucleus test. In order to evaluate a primary and repairable DNA damage, the comet assay has been also included. In spite of their potential hazardous chemical structure, a lack of mutagenicity was observed for both compounds in all bacterial strains tested, also in presence of the exogenous metabolic activator, showing that no genotoxic derivatives were produced by CYP450-mediated biotransformations. Neither genotoxicity at chromosomal level (i.e. clastogenicity or aneuploidy) nor single-strand breaks were observed. These findings will be useful in further assessing the safety of HCA and BMHCA as either flavour or fragrance chemicals. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Borax counteracts genotoxicity of aluminum in rat liver.

    Science.gov (United States)

    Turkez, Hasan; Geyikoğlu, Fatime; Tatar, Abdulgani

    2013-10-01

    This study was carried out to evaluate the protective role of borax (BX) on genotoxicity induced by aluminum (Al) in rat liver, using liver micronucleus assay as an indicator of genotoxicity. Sprague-Dawley rats were randomly separated into six groups and each group had four animals. Aluminum chloride (AlCl₃; 5 mg/kg b.w.) and BX (3.25 and 13 mg/kg b.w.) were injected intraperitoneally to rats. Besides, animals were also treated with Al for 4 consecutive days followed by BX for 10 days. Rats were anesthetized after Al and BX injections and the hepatocytes were isolated for counting the number of micronucleated hepatocytes (MNHEPs). AlCl₃ was found to significantly (p < 0.05) increase the number of MNHEPs. Rats treated with BX, however, showed no increase in MNHEPs. Moreover, simultaneous treatments with BX significantly modulated the genotoxic effects of AlCl₃ in rats. It can be concluded that BX has beneficial influences and has the ability to antagonize Al toxicity.

  8. Molecular and cytogenetic assessment of Dipterygium glaucum genotoxicity

    Directory of Open Access Journals (Sweden)

    NADA H. ALTWATY

    2016-01-01

    Full Text Available ABSTRACT The aim of the present study is to assess the genotoxicity of Dipterygium glaucum grows widely in Saudi Arabia desert to produce safety herbal products. This work is considered the first and pioneer report so far due to the lack and poor evaluated reports of the plant species for their mutagensity, genotoxicity and cytogenetics effects. Cytogenetic effects of D. glaucum on mitotic in roots of Vicia faba showed reduction in mitotic activity using three extracts; water, ethanol and ethyl acetate. Chromosomal abnormalities were recorded that included stickiness of chromosomes, chromatin bridge, fragments, lagging chromosome and micronuclei. Protein bands and RAPD analyses of V. faba treated with three D. glaucum extracts revealed some newly induced proteins and DNA fragments and other disappeared. Chemical constitution of the plant species should be identified with their biological activities against human and animal cells like HeLa cancer cell line. We are recommending using additional genotoxicity tests and other toxicity tests on animal culture with different concentrations and also utilizing several drought and heat tolerant genes of the plant species in gene cloning to develop and improve other economical crop plants instead of using the species as oral herbal remedy

  9. Genotoxicity risk assessment of diversely substituted quinolines using the SOS chromotest.

    Science.gov (United States)

    Duran, Leidy Tatiana Díaz; Rincón, Nathalia Olivar; Galvis, Carlos Eduardo Puerto; Kouznetsov, Vladimir V; Lorenzo, Jorge Luis Fuentes

    2015-03-01

    Quinolines are aromatic nitrogen compounds with wide therapeutic potential to treat parasitic and microbial diseases. In this study, the genotoxicity of quinoline, 4-methylquinoline, 4-nitroquinoline-1-oxide (4-NQO), and diversely functionalized quinoline derivatives and the influence of the substituents (functional groups and/or atoms) on their genotoxicity were tested using the SOS chromotest. Quinoline derivatives that induce genotoxicity by the formation of an enamine epoxide structure did not induce the SOS response in Escherichia coli PQ37 cells, with the exception of 4-methylquinoline that was weakly genotoxic. The chemical nature of the substitution (C-5 to C-8: hydroxyl, nitro, methyl, isopropyl, chlorine, fluorine, and iodine atoms; C-2: phenyl and 3,4-methylenedioxyphenyl rings) of quinoline skeleton did not significantly modify compound genotoxicities; however, C-2 substitution with α-, β-, or γ-pyridinyl groups removed 4-methylquinoline genotoxicity. On the other hand, 4-NQO derivatives whose genotoxic mechanism involves reduction of the C-4 nitro group were strong inducers of the SOS response. Methyl and nitrophenyl substituents at C-2 of 4-NQO core affected the genotoxic potency of this molecule. The relevance of these results is discussed in relation to the potential use of the substituted quinolines. The work showed the sensitivity of SOS chromotest for studying structure-genotoxicity relationships and bioassay-guided quinoline synthesis. © 2013 Wiley Periodicals, Inc.

  10. Workshop. Assessment of Occupational and Environmental Exposure to Genotoxic Substances - a Methodological Approach

    International Nuclear Information System (INIS)

    2000-01-01

    During the workshop various works concerning radiobiology, environmental and occupational medicine were presented. Exposure to genotoxic and carcinogenic agents, like ionizing radiation, aromatic hydrocarbons, herbicides, pesticides was investigated

  11. New investigations into the genotoxicity of cobalt compounds and their impact on overall assessment of genotoxic risk

    OpenAIRE

    Kirkland, David; Brock, Tom; Haddouk, Hasnaà; Hargeaves, Victoria; Lloyd, Melvyn; Mc Garry, Sarah; Proudlock, Raymond; Sarlang, Séverine; Sewald, Katherina; Sire, Guillaume; Sokolowski, Andrea; Ziemann, Christina

    2015-01-01

    The genotoxicity of cobalt metal and cobalt compounds has been widely studied. Several publications show induction of chromosomal aberrations, micronuclei or DNA damage in mammalian cells in vitro in the absence of S9. Mixed results were seen in gene mutation studies in bacteria and mammalian cells in vitro, and in chromosomal aberration or micronucleus assays in vivo. To resolve these inconsistencies, new studies were performed with soluble and poorly soluble cobalt compounds according to OE...

  12. Storage array reflection considerations

    International Nuclear Information System (INIS)

    Haire, M.J.; Jordan, W.C.; Taylor, R.G.

    1997-01-01

    The assumptions used for reflection conditions of single containers are fairly well established and consistently applied throughout the industry in nuclear criticality safety evaluations. Containers are usually considered to be either fully water reflected (i.e., surrounded by 6 to 12 in. of water) for safety calculations or reflected by 1 in. of water for nominal (structural material and air) conditions. Tables and figures are usually available for performing comparative evaluations of containers under various loading conditions. Reflection considerations used for evaluating the safety of storage arrays of fissile material are not as well established. When evaluating arrays, it has become more common for analysts to use calculations to demonstrate the safety of the array configuration. In performing these calculations, the analyst has considerable freedom concerning the assumptions made for modeling the reflection of the array. Considerations are given for the physical layout of the array with little or no discussion (or demonstration) of what conditions are bounded by the assumed reflection conditions. For example, an array may be generically evaluated by placing it in a corner of a room in which the opposing walls are far away. Typically, it is believed that complete flooding of the room is incredible, so the array is evaluated for various levels of water mist interspersed among array containers. This paper discusses some assumptions that are made regarding storage array reflection

  13. High throughput comet assay to study genotoxicity of nanomaterials

    Directory of Open Access Journals (Sweden)

    Naouale El Yamani

    2015-06-01

    Full Text Available The unique physicochemical properties of engineered nanomaterials (NMs have accelerated their use in diverse industrial and domestic products. Although their presence in consumer products represents a major concern for public health safety, their potential impact on human health is poorly understood. There is therefore an urgent need to clarify the toxic effects of NMs and to elucidate the mechanisms involved. In view of the large number of NMs currently being used, high throughput (HTP screening technologies are clearly needed for efficient assessment of toxicity. The comet assay is the most used method in nanogenotoxicity studies and has great potential for increasing throughput as it is fast, versatile and robust; simple technical modifications of the assay make it possible to test many compounds (NMs in a single experiment. The standard gel of 70-100 μL contains thousands of cells, of which only a tiny fraction are actually scored. Reducing the gel to a volume of 5 μL, with just a few hundred cells, allows twelve gels to be set on a standard slide, or 96 as a standard 8x12 array. For the 12 gel format, standard slides precoated with agarose are placed on a metal template and gels are set on the positions marked on the template. The HTP comet assay, incorporating digestion of DNA with formamidopyrimidine DNA glycosylase (FPG to detect oxidised purines, has recently been applied to study the potential induction of genotoxicity by NMs via reactive oxygen. In the NanoTEST project we investigated the genotoxic potential of several well-characterized metal and polymeric nanoparticles with the comet assay. All in vitro studies were harmonized; i.e. NMs were from the same batch, and identical dispersion protocols, exposure time, concentration range, culture conditions, and time-courses were used. As a kidney model, Cos-1 fibroblast-like kidney cells were treated with different concentrations of iron oxide NMs, and cells embedded in minigels (12

  14. Genotoxicity of 1,3-dichloro-2-propanol in the SOS chromotest and in the Ames test. Elucidation of the genotoxic mechanism.

    Science.gov (United States)

    Hahn, H; Eder, E; Deininger, C

    1991-01-01

    1,3-Dichloro-2-propanol (1,3-DCP-OH, glycerol dichlorohydrin) is of great importance in many industrial processes and has been detected in foodstuffs, in particular in soup spices and instant soups. It has been shown to be carcinogenic, genotoxic and mutagenic. Its genotoxic mechanisms are, however, not yet entirely understood. We have investigated whether alcohol dehydrogenase (ADH) catalysed activation to the highly mutagenic and carcinogenic 1,3-dichloroacetone or formation of epichlorohydrin or other genotoxic compounds play a role for mutagenicity and genotoxicity. In our studies, no indications of ADH catalysed formation of 1,3-dichloropropane could be found, although we could demonstrate a clear activation by ADH in the case of 2-chloropropenol. Formation of allyl chloride could also be excluded. We found, however, clear evidence that epichlorohydrin formed chemically in the buffer and medium used in the test is responsible for genotoxicity. No indication was found that enzymatic formation of epichlorohydrin plays a role. Additional mutagenicity and genotoxicity studies with epichlorohydrin also confirmed the hypothesis that genotoxic effects of 1,3-DCP-OH depend on the chemical formation of epichlorohydrin.

  15. Observations of the effect of atmospheric processes on the genotoxic potency of airborne particulate matter

    DEFF Research Database (Denmark)

    Feilberg, Anders; Nielsen, Torben; Binderup, Mona-Lise

    2002-01-01

    In this study, the relationship between genotoxic potency and the occurrence of polycyclic aromatic hydrocarbons (PAH), including benzo(a)pyrene (BaP), and nitro-PAH in urban and semi-rural air masses has been investigated. The Salmonella/microsome assay has been used as a measure of genotoxic po...

  16. Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice

    DEFF Research Database (Denmark)

    Modrzynska, Justyna; Berthing, Trine; Ravn-Haren, Gitte

    2018-01-01

    Background Little is known about the mechanism underlying the genotoxicity observed in the liver following pulmonary exposure to carbon black (CB) nanoparticles (NPs). The genotoxicity could be caused by the presence of translocated particles or by circulating inflammatory mediators released during...

  17. Proteome-wide Identification of Poly(ADP-Ribosyl)ation Targets in Different Genotoxic Stress Responses

    DEFF Research Database (Denmark)

    Jungmichel, S.; Rosenthal, F.; Altmeyer, M.

    2013-01-01

    . Nuclear proteins encompassing nucleic acid binding properties are prominently PARylated upon genotoxic stress, consistent with the nuclear localization of ARTD1/PARP1 and ARTD2/PARP2. Distinct differences in proteins becoming PARylated upon various genotoxic insults are observed, exemplified...

  18. Lack of genotoxicity in vivo for food color additive Tartrazine.

    Science.gov (United States)

    Bastaki, Maria; Farrell, Thomas; Bhusari, Sachin; Pant, Kamala; Kulkarni, Rohan

    2017-07-01

    Tartrazine is approved as a food color additive internationally with INS number 102, in the United States as food color subject to batch certification "Food, Drug, and Cosmetic" (FD&C) Yellow No. 5, and in Europe as food color additive with E number 102. In their evaluation of the color (2013), the European Food Safety Authority (EFSA) expressed concerns of potential genotoxicity, based primarily on one genotoxicity study that was not conducted according to Guidelines. The present in vivo genotoxicity study was conducted according to OECD Guidelines in response to EFSA's request for additional data. The animal species and strain, and the tissues examined were selected specifically to address the previously reported findings. The results of this study show clear absence of genotoxic activity for Tartrazine, in the bone marrow micronucleus assay and the Comet assay in the liver, stomach, and colon. These data addressed EFSA's concerns for genotoxicity. The Joint WHO/FAO Committee on Food Additives (JECFA) (2016) also reviewed these data and concluded that there is no genotoxicity concern for Tartrazine. Negative findings in parallel genotoxicity studies on Allura Red AC and Ponceau 4R (published separately) are consistent with lack of genotoxicity for azo dyes used as food colors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Interpretation of the margin of exposure for genotoxic carcinogens - elicitation of expert knowledge about the form of the dose response curve at human relevant exposures.

    Science.gov (United States)

    Boobis, Alan; Flari, Villie; Gosling, John Paul; Hart, Andy; Craig, Peter; Rushton, Lesley; Idahosa-Taylor, Ehi

    2013-07-01

    The general approach to risk assessment of genotoxic carcinogens has been to advise reduction of exposure to "as low as reasonably achievable/practicable" (ALARA/P). However, whilst this remains the preferred risk management option, it does not provide guidance on the urgency or extent of risk management actions necessary. To address this, the "Margin of Exposure" (MOE) approach has been proposed. The MOE is the ratio between the point of departure for carcinogenesis and estimated human exposure. However, interpretation of the MOE requires implicit or explicit consideration of the shape of the dose-response curve at human relevant exposures. In a structured elicitation exercise, we captured expert opinion on available scientific evidence for low dose-response relationships for genotoxic carcinogens. This allowed assessment of: available evidence for the nature of dose-response relationships at human relevant exposures; the generality of judgments about such dose-response relationships; uncertainties affecting judgments on the nature of such dose-response relationships; and whether this last should differ for different classes of genotoxic carcinogens. Elicitation results reflected the variability in experts' views on the form of the dose-response curve for low dose exposure and major sources of uncertainty affecting the assumption of a linear relationship. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Screening potential genotoxic effect of aquatic plant extracts using the mussel micronucleus test

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    Bettina Eck-Varanka

    2016-01-01

    Full Text Available Objective: To assess the genotoxic potential of selected aquatic macrophytes: Ceratophyllum demersum L. (hornwort, family Ceratophyllaceae, Typha angustifolia L. (narrowleaf cattail, family Typhaceae, Stratiotes aloides L. (water soldier, family Butomaceae, and Oenanthe aquatica (L. Poir. (water dropwort, family Umbelliferae. Methods: For genotoxicity assessment, the mussel micronucleus test was applied. Micronucleus frequency was determined from the haemolymph of Unio pictorum L. (painter’s mussel. In parallel, total and hydrolisable tannin contents were determined. Results: All plant extracts elucidated significant mutagenic effect. Significant correlation was determined between tannin content and mutagenic capacity. Conclusions: The significant correlation between genotoxicity as expressed by micronucleus frequency and tannin content (both total and hydrolisable tannins indicate that tannin is amongst the main compounds being responsible for the genotoxic potential. It might be suggested that genotoxic capacity of these plants elucidate a real ecological effect in the ecosystem.

  1. Anti-Genotoxic Potential of Bilirubin In Vivo

    DEFF Research Database (Denmark)

    Wallner, Marlies; Antl, Nadja; Rittmannsberger, Barbara

    2013-01-01

    The bile pigment bilirubin is a known antioxidant and is associated with protection from cancer and cardiovascular disease (CVD) when present in too strong concentrations. Unconjugated bilirubin (UCB) might also possess anti-genotoxic potential by preventing oxidative damage to DNA. Moderately...... elevated bilirubin levels are found in individuals with Gilbert syndrome and more severe in the hyperbilirubinemic Gunn rat model. This study was therefore aimed to assess the levels of oxidative damage to DNA in Gilbert syndrome subjects and Gunn rats compared to matched controls. Seventy-six individuals...

  2. Genotoxic thresholds, DNA repair, and susceptibility in human populations

    International Nuclear Information System (INIS)

    Jenkins, Gareth J.S.; Zair, Zoulikha; Johnson, George E.; Doak, Shareen H.

    2010-01-01

    It has been long assumed that DNA damage is induced in a linear manner with respect to the dose of a direct acting genotoxin. Thus, it is implied that direct acting genotoxic agents induce DNA damage at even the lowest of concentrations and that no 'safe' dose range exists. The linear (non-threshold) paradigm has led to the one-hit model being developed. This 'one hit' scenario can be interpreted such that a single DNA damaging event in a cell has the capability to induce a single point mutation in that cell which could (if positioned in a key growth controlling gene) lead to increased proliferation, leading ultimately to the formation of a tumour. There are many groups (including our own) who, for a decade or more, have argued, that low dose exposures to direct acting genotoxins may be tolerated by cells through homeostatic mechanisms such as DNA repair. This argument stems from the existence of evolutionary adaptive mechanisms that allow organisms to adapt to low levels of exogenous sources of genotoxins. We have been particularly interested in the genotoxic effects of known mutagens at low dose exposures in human cells and have identified for the first time, in vitro genotoxic thresholds for several mutagenic alkylating agents (Doak et al., 2007). Our working hypothesis is that DNA repair is primarily responsible for these thresholded effects at low doses by removing low levels of DNA damage but becoming saturated at higher doses. We are currently assessing the roles of base excision repair (BER) and methylguanine-DNA methyltransferase (MGMT) for roles in the identified thresholds (Doak et al., 2008). This research area is currently important as it assesses whether 'safe' exposure levels to mutagenic chemicals can exist and allows risk assessment using appropriate safety factors to define such exposure levels. Given human variation, the mechanistic basis for genotoxic thresholds (e.g. DNA repair) has to be well defined in order that susceptible individuals are

  3. The comet assay in testing the potential genotoxicity of nanomaterials

    Directory of Open Access Journals (Sweden)

    Amaya Azqueta

    2015-06-01

    Full Text Available In the last two decades the production and use of nanomaterials (NMs has impressively increased. Their small size, given a mass equal to that of the corresponding bulk material, implies an increase in the surface area and consequently in the number of atoms that can be reactive. They possess different physical, chemical and biological properties compared to bulk materials of the same composition, which makes them very interesting and valuable for many different applications in technology, energy, construction, electronics, agriculture, optics, paints, textiles, food, cosmetics, medicine... Toxicological assessment of NMs is crucial; the same properties that make them interesting also make them potentially harmful for health and the environment. However, the term NM covers many different kinds of particle , and so there is no simple, standard approach to assessing their toxicity. NMs can enter the cell, interact with cell components and even penetrate the nucleus and interfere with the genetic material. Among the different branches of toxicology, genotoxicity is a main area of concern since it is closely related with the carcinogenic potential of compounds. The Organisation for Economic Co-operation and Development (OECD has published internationally agreed in vitro and in vivo validated test methods to evaluate different genotoxic endpoints of chemicals, including chromosome and gene mutations, and DNA breaks. However not all the assays are suitable to study the genotoxic potential of NMs as has been shown by the OECD Working Party on Manufactured Nanomaterials (WPMN. Moreover, alterations to DNA bases, which are precursors to mutations and of great importance in elucidating the mechanism of action of NMs, are not covered by the OECD guidelines. The in vivo standard comet assay (which measures DNA breaks and alkali-labile sites was included in the OECD assays battery in September 2014 while the in vitro standard comet assay is currently under

  4. Genotoxicity studies in semiconductor industry. 1. In vitro mutagenicity and genotoxicity studies of waste samples resulting from plasma etching

    Energy Technology Data Exchange (ETDEWEB)

    Braun, R.; Huettner, E.M.; Merten, H.; Raabe, F. (Institute of Plant Genetics and Crop Plant Research, Gatersleben (Germany))

    1993-07-01

    Solid waste samples taken from the etching reactor, the turbo pump, and the waste air system of a plasma etching technology line in semiconductor production were studied as to their genotoxic properties in a bacterial repair test, in the Ames/Salmonella microsome assay, in the SOS chromotest, in primary mouse hepatocytes, and in Chinese hamster V79 cell cultures. All three waste samples were found to be active by inducing of unscheduled DNA-synthesis in mouse hepatocytes in vitro. In the bacterial rec-type repair test with Proteus mirabilis, waste samples taken from the turbo pump and the vacuum pipe system were not genotoxic. The waste sample taken from the chlorine-mediated plasma reactor was clearly positive in the bacterial repair assay and in the SOS chromotest with Escherichia coli. Mutagenic activity was demonstrated for all samples in the presence and absence of S9 mix made from mouse liver homogenate. Again, highest mutagenic activity was recorded for the waste sample taken from the plasma reactor, while samples collected from the turbo pump and from the waste air system before dilution and liberation of the air were less mutagenic. For all samples chromosomal damage in V79 cells was not detected, indicating absence of clastogenic activity in vitro. Altogether, these results indicate generation of genotoxic and mutagenic products as a consequence of chlorine-mediated plasma etching in the microelectronics industry and the presence of genotoxins even in places distant from the plasma reactor. Occupational exposure can be expected both from the precipitated wastes and from chemicals reaching the environment with the air stream.

  5. In vivo genotoxicity assessment of acrylamide and glycidyl methacrylate.

    Science.gov (United States)

    Dobrovolsky, Vasily N; Pacheco-Martinez, M Monserrat; McDaniel, L Patrice; Pearce, Mason G; Ding, Wei

    2016-01-01

    Acrylamide (ACR) and glycidyl methacrylate (GMA) are structurally related compounds used for making polymers with various properties. Both chemicals can be present in food either as a byproduct of processing or a constituent of packaging. We performed a comprehensive evaluation of ACR and GMA genotoxicity in Fisher 344 rats using repeated gavage administrations. Clastogenicity was measured by scoring micronucleated (MN) erythrocytes from peripheral blood, DNA damage in liver, bone marrow and kidneys was measured using the Comet assay, and gene mutation was measured using the red blood cell (RBC) and reticulocyte Pig-a assay. A limited histopathology evaluation was performed in order to determine levels of cytotoxicity. Doses of up to 20 mg/kg/day of ACR and up to 250 mg/kg/day of GMA were used. ACR treatment resulted in DNA damage in the liver, but not in the bone marrow. While ACR was not a clastogen, it was a weak (equivocal) mutagen in the cells of bone marrow. GMA caused DNA damage in the cells of bone marrow, liver and kidney, and induced MN reticulocytes and Pig-a mutant RBCs in a dose-dependent manner. Collectively, our data suggest that both compounds are in vivo genotoxins, but the genotoxicity of ACR is tissue specific. Published by Elsevier Ltd.

  6. Evaluation of environmental genotoxicity by comet assay in Columba livia.

    Science.gov (United States)

    González-Acevedo, Anahi; García-Salas, Juan A; Gosálvez, Jaime; Fernández, José Luis; Dávila-Rodríguez, Martha I; Cerda-Flores, Ricardo M; Méndez-López, Luis F; Cortés-Gutiérrez, Elva I

    2016-01-01

    The concentrations of recognized or suspected genotoxic and carcinogenic agents found in the air of large cities and, in particular, developing countries, have raised concerns about the potential for chronic health effects in the populations exposed to them. The biomonitoring of environmental genotoxicity requires the selection of representative organisms as "sentinels," as well as the development of suitable and sensitive assays, such as those aimed at assessing DNA damage. The aim of this study was to evaluate DNA damage levels in erythrocytes from Columba livia living in the metropolitan area of Monterrey, Mexico, compared with control animals via comet assay, and to confirm the results via Micronuclei test (MN) and DNA breakage detection-fluorescence in situ hybridization (DBD-FISH). Our results showed a significant increase in DNA migration in animals from the area assayed compared with that observed in control animals sampled in non-contaminated areas. These results were confirmed by MN test and DBD-FISH. In conclusion, these observations confirm that the examination of erythrocytes from Columba livia via alkaline comet assay provides a sensitive and reliable end point for the detection of environmental genotoxicants.

  7. Genotoxicity of corrosion eluates obtained from orthodontic brackets in vitro.

    Science.gov (United States)

    Angelieri, Fernanda; Marcondes, Joao Paulo C; de Almeida, Danielle Cristina; Salvadori, Daisy M F; Ribeiro, Daniel A

    2011-04-01

    The purpose of this study was to evaluate whether corrosion eluates obtained from commercially available orthodontic brackets are able to induce genetic damage in vitro. Genotoxicity was assessed by the single cell gel (comet) assay using Chinese hamster ovary (CHO) cells. The following orthodontic metallic brackets were used: Morelli (Sorocaba, Brazil); Abzil (São José do Rio Preto, Brazil); Dentaurum (Pforzheim, Germany); and 3M Unitek (Puchheim, Germany). Each dental bracket was submitted to a corrosion process in a solution containing equal amounts of acetic acid and sodium chloride at 0.1 M concentration for 1, 3, 7, 14, 21, 35, and 70 days. CHO cells were exposed to eluates for 30 minutes at 37°C. The negative control was treated with the same solution used for corrosion process for 30 minutes at 37°C. Independent positive control was performed with methyl methanesulfonate (MMS) (Sigma Aldrich, St. Louis, Mo) at 1 ug/mL for 1 hour. None of the eluates was found to exhibit genotoxicity, regardless of the different commercial brands of orthodontic appliance used. In summary, our results indicate corrosion eluates obtained from orthodontic brackets do not induce genetic damage as assessed by single cell gel (comet) assay. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  8. Histopathological and genotoxic effects of chlorpyrifos in rats.

    Science.gov (United States)

    Ezzi, Lobna; Belhadj Salah, Imen; Haouas, Zohra; Sakly, Amina; Grissa, Intissar; Chakroun, Sana; Kerkeni, Emna; Hassine, Mohsen; Mehdi, Meriem; Ben Cheikh, Hassen

    2016-03-01

    This study aims to investigate the effects of chlorpyrifos's sub-acute exposure on male rats. Two groups with six animals each were orally treated, respectively, with 3.1 mg/kg b w and 6.2 mg/kg b w of chlorpyrifos during 4 weeks. The genotoxic effect of chlopyrifos was investigated using the comet assay and the micronucleus test. Some hematological and liver's histopathological changes were also evaluated. Results revealed that chlorpyrifos induced histopathological alterations in liver parenchyma. The lymphoid infiltration observed in liver sections and the increase in white blood cells parameter are signs of inflammation. A significant increase in the platelet' count and in polychromatic erythrocytes/normochromatic erythrocytes (PCE/NCE) ratio was observed in chlorpyrifos-treated groups which could be due to the stimulatory effect of chlorpyrifos on cell formation in the bone marrow at lower doses. In addition, the increase of bone marrow micronucleus percentage and the comet tail length revealed a genotoxic potential of chlorpyrifos in vivo.

  9. Genotoxicity of formaldehyde: Molecular basis of DNA damage and mutation

    Directory of Open Access Journals (Sweden)

    Masanobu eKawanishi

    2014-09-01

    Full Text Available Formaldehyde is commonly used in the chemical industry and is present in the environment, such as vehicle emissions, some building materials, food and tobacco smoke. It also occurs as a natural product in most organisms, the sources of which include a number of metabolic processes. It causes various acute and chronic adverse effects in humans if they inhale its fumes. Among the chronic effects on human health, we summarize data on genotoxicity and carcinogenicity in this review, and we particularly focus on the molecular mechanisms involved in the formaldehyde mutagenesis. Formaldehyde mainly induces N-hydroxymethyl mono-adducts on guanine, adenine and cytosine, and N-methylene crosslinks between adjacent purines in DNA. These crosslinks are types of DNA damage potentially fatal for cell survival if they are not removed by the nucleotide excision repair pathway. In the previous studies, we showed evidence that formaldehyde causes intra-strand crosslinks between purines in DNA using a unique method (Matsuda et al. Nucleic Acids Res. 26, 1769-1774,1998. Using shuttle vector plasmids, we also showed that formaldehyde as well as acetaldehyde induces tandem base substitutions, mainly at 5’-GG and 5’-GA sequences, which would arise from the intra-strand crosslinks. These mutation features are different from those of other aldehydes such as crotonaldehyde, acrolein, glyoxal and methylglyoxal. These findings provide molecular clues to improve our understanding of the genotoxicity and carcinogenicity of formaldehyde.

  10. The genotoxic effect of oxcarbazepine on mice blood lymphocytes.

    Science.gov (United States)

    Akbar, Huma; Khan, Ajmal; Mohammadzai, Imdadullah; Khisroon, Muhammad; Begum, Ilham

    2018-04-01

    This study was conducted to assess the amount of DNA damage caused by Oxcarbazepine (OXC) through single cell gel electrophoresis (SCGE) technique/comet assay. OXC derived from dibenzazepine series is an effective second generation antiepileptic drug (AED) for both children and adults. Side effects like genotoxic effects of AEDs are of prime importance resulting from toxic metabolites, free radicals and reactive oxygen species (ROS). Forty Eight adult male Bagg's albino mice (BALB/c) were randomly classified into eight groups, each comprising of six animals. Two of these groups were control and six were tested groups. Control groups were injected with 1% tween 80 while tested groups were injected with 10, 20, and 40 mg/kg-day OXC for seven days (acute therapy) and 28 days (subchronic therapy) in peritoneal cavity. Blood samples were collected by cardiac puncture and subjected to comet assay for the analysis of DNA damage. Per sample 100 cells were scored and classified according to comet tail length. The results showed that OXC in acute and long term therapies had significantly higher (p < 0.05) genotoxicity in treated groups as compared to control groups. Our study suggests that OXC may cause significant DNA damage in both acute as well as in subchronic therapies.

  11. Hexavalent chromium is cytotoxic and genotoxic to American alligator cells.

    Science.gov (United States)

    Wise, Sandra S; Wise, Catherine; Xie, Hong; Guillette, Louis J; Zhu, Cairong; Wise, John Pierce; Wise, John Pierce

    2016-02-01

    Metals are a common pollutant in the aquatic ecosystem. With global climate change, these levels are anticipated to rise as lower pH levels allow sediment bound metals to be released. The American alligator (Alligator mississippiensis) is an apex predator in the aquatic ecosystem and is considered a keystone species; as such it serves as a suitable monitor for localized pollution. One metal of increasing concern is hexavalent chromium (Cr(VI)). It is present in the aquatic environment and is a known human carcinogen and reproductive toxicant. We measured the cytotoxicity and genotoxicity of Cr(VI) in American alligator cells derived from scute tissue. We found that particulate and soluble Cr(VI) are both cytotoxic and genotoxic to alligator cells in a concentration-dependent manner. These data suggest that alligators may be used as a model for assessing the effects of environmental Cr(VI) contamination as well as for other metals of concern. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Genotoxic effects of bismuth (III oxide nanoparticles by comet assay

    Directory of Open Access Journals (Sweden)

    Reecep Liman

    2015-06-01

    Full Text Available Bismuth oxide is one of the important transition metal oxides and it has been intensively studied due to their peculiar characteristics (semiconductor band gap, high refractive index, high dielectric permittivity, high oxygen conductivity, resistivity, photoconductivity and photoluminescence etc.. Therefore, it is used such as microelectronics, sensor technology, optical coatings, transparent ceramic glass manufacturing, nanoenergetic gas generator, biosensor for DNA hybridization, potential immobilizing platforms for glucose oxidase and polyphenol oxidase, fuel cells, a additive in paints, an astringent in a variety of medical creams and topical ointments, and for the determination of heavy metal ions in drinking water, mineral water and urine. In addition this, Bismuth (III oxide nanoparticles (BONPs are favorable for the biomolecules adsorption than regular sized particles because of their greater advantages and novel characteristics (much higher specific surface, greater surface free energy, and good electrochemical stability etc.. Genotoxic effects of BONPs were investigated on the root cells of Allium cepa by Comet assay. A. cepa roots were treated with the aqueous dispersions of BONPs at 5 different concentrations (12.5, 25, 50, 75, and 100 ppm for 4 h. A significant increase in DNA damage was also observed at all concentrations of BONPs except 12.5 ppm by Comet assay. The results were also analyzed statistically by using SPSS for Windows; Duncan’s multiple range test was performed. These result indicate that BONPs exhibit genotoxic activity in A. cepa root meristematic cells.

  13. Nanoceria have no genotoxic effect on human lens epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Pierscionek, Barbara K; Yasseen, Akeel A [School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA (United Kingdom); Li, Yuebin; Schachar, Ronald A; Chen, Wei [Department of Physics, University of Texas at Arlington, Arlington, TX 76019 (United States); Colhoun, Liza M, E-mail: b.pierscionek@ulster.ac.uk, E-mail: weichen@uta.edu [Centre for Vision and Vascular Sciences, School of Medicine, Dentistry and Biomedical Sciences, Queen' s University Belfast, Grosvenor Road, Belfast, BT12 6BA (United Kingdom)

    2010-01-22

    There are no treatments for reversing or halting cataract, a disease of the structural proteins in the eye lens, that has associations with other age-related degenerative conditions such as Alzheimer's disease. The incidence of cataract and associated conditions is increasing as the average age of the population rises. Protein folding diseases are difficult to assess in vivo as proteins and their age-related changes are assessed after extraction. Nanotechnology can be used to investigate protein changes in the intact lens as well as for a potential means of drug delivery. Nanoparticles, such as cerium oxide (CeO{sub 2}) which have antioxidant properties, may even be used as a means of treating cataract directly. Prior to use in treatments, nanoparticle genotoxicity must be tested to assess the extent of any DNA or chromosomal damage. Sister chromatid exchanges were measured and DNA damage investigated using the alkaline COMET assay on cultured human lens epithelial cells, exposed to 5 and 10 {mu}g ml{sup -1} of CeO{sub 2} nanoparticles (nanoceria). Nanoceria at these dosages did not cause any DNA damage or significant increases in the number of sister chromatid exchanges. The absence of genotoxic effects on lens cells suggests that nanoceria, in the doses and exposures tested in this study, are not deleterious to the eye lens and have the potential for use in studying structural alterations, in developing non-surgical cataract treatments and in investigating other protein folding diseases.

  14. Genotoxic action of sunlight upon Bacillus subtilis spores

    International Nuclear Information System (INIS)

    Munakata, Nobuo

    1989-01-01

    Samples of Bacillus subtilis spores dried on membrane filter were exposed to natural sunlight from solar-noon time at Tokyo. The survival and mutation induction of wild-type (UVR) and repair-deficient (UVS) spores were determined on 66 occasions since 1979. Two of the values were considered to be useful in monitoring solar UV intensity; the inverse of the time (in minutes) of exposure to kill 63% of the UVS spores ('sporocidal index') and the induced mutation frequency at 60 minutes of exposure of the UVR spores ('mutagenic index'). Both values were varied greatly due to time of a year, weather and other conditions. Estimates of year-round changes under clear skies were obtained by connecting the maximum values attained in these years. In these curves, there are more than 7-fold differences in the genotoxicity between winter and summer months, with major increases observed in early spring and decreases through autumn. Using a series of UV cut-off filters, the wavelengths most effective for the sporocidal actions were estimated to be in the range of 308 - 325 nm, shorter wavelengths being effective when the genotoxicity was higher. Sunburn meter of Robertson-Berger type seems to respond to slightly longer wavelength components of the solar spectrum. However, a reasonable correlation was obtained between the reading of the meter and the sporocidal index. (author)

  15. Genotoxicity evaluation of HMG CoA reductase inhibitor rosuvastatin.

    Science.gov (United States)

    Berber, Ahmet Ali; Celik, Mustafa; Aksoy, Hüseyin

    2014-07-01

    The genotoxic potential of rosuvastatin as one of the statin drugs was assessed by chromosomal aberrations (CAs), micronucleus (MN) and DNA damage by comet assay in the human peripheral blood lymphocytes. Rosuvastatin was used at concentrations of 0.0625, 0.125, 0.25, 0.5 and 1 µg/mL for these in vitro assays. In all assays, a negative and positive control were also included. CA frequencies were significantly increased in all concentrations at 24 hours and significantly increased in all concentrations except 0.0625 µg/mL at 48 hours, compared to the negative control. Rosuvastatin has a decreased mitotic index (MI) at 0.5- and 1-µg/mL concentrations at 24 hours and at 0.25, 0.5 and 1 µg/mL at 48 hours. A significant increase was observed for induction of MN in all treatments, compared to the negative control. Cytokinesis-block proliferation indices were not affected by treatments with rosuvastatin. In the comet assay, significant increases in comet tail length and tail moment were observed at 0.0625-, 0.5- and 1-µg/mL concentrations. Comet intensity was significantly increased in all concentrations except 0.0625 µg/mL. According to these results, rosuvastatin is cytotoxic and clastogenic/aneugenic in human peripheral lymphocytes. Further studies should be conducted in other test systems to evaluate the full genotoxic potential of rosuvastatin.

  16. Comparative Genotoxicity of Cadmium and Lead in Earthworm Coelomocytes

    Directory of Open Access Journals (Sweden)

    Ptumporn Muangphra

    2011-01-01

    Full Text Available To determine genotoxicity to coelomocytes, Pheretima peguana earthworms were exposed in filter paper studies to cadmium (Cd and lead (Pb for 48 h, at concentrations less than the LC10—Cd: 0.09, 0.19, 0.38, 0.75, and 1.50 μg cm−2; Pb: 1.65, 3.29, 6.58, 13.16, and 26.32 μg cm−2. For Cd at 0.75 μg cm−2, in the micronucleus test (detects chromosomal aberrations, significant increases (<.05 in micronuclei and binucleate cells were observed, and in the comet assay (detects DNA single-strand breaks, tail DNA% was significantly increased. Lead was less toxic with minimal effects on DNA, but the binucleates were significantly increased by Pb at 3.29 μg cm−2. This study shows that Cd is more acutely toxic and sublethally genotoxic than Pb to P. peguana. Cadmium caused chromosomal aberrations and DNA single-strand breaks at 45% of the LC10 concentration. Lead, in contrast, did not induce DNA damage but caused cytokinesis defects.

  17. Genotoxicity of Nicotiana tabacum leaves on Helix aspersa.

    Science.gov (United States)

    da Silva, Fernanda R; Erdtmann, Bernardo; Dalpiaz, Tiago; Nunes, Emilene; Ferraz, Alexandre; Martins, Tales L C; Dias, Johny F; da Rosa, Darlan P; Porawskie, Marilene; Bona, Silvia; da Silva, Juliana

    2013-07-01

    Tobacco farmers are routinely exposed to complex mixtures of inorganic and organic chemicals present in tobacco leaves. In this study, we examined the genotoxicity of tobacco leaves in the snail Helix aspersa as a measure of the risk to human health. DNA damage was evaluated using the micronucleus test and the Comet assay and the concentration of cytochrome P450 enzymes was estimated. Two groups of snails were studied: one fed on tobacco leaves and one fed on lettuce (Lactuca sativa L) leaves (control group). All of the snails received leaves (tobacco and lettuce leaves were the only food provided) and water ad libitum. Hemolymph cells were collected after 0, 24, 48 and 72 h. The Comet assay and micronucleus test showed that exposure to tobacco leaves for different periods of time caused significant DNA damage. Inhibition of cytochrome P450 enzymes occurred only in the tobacco group. Chemical analysis indicated the presence of the alkaloid nicotine, coumarins, saponins, flavonoids and various metals. These results show that tobacco leaves are genotoxic in H. aspersa and inhibit cytochrome P450 activity, probably through the action of the complex chemical mixture present in the plant.

  18. Genotoxicity of Nicotiana tabacum leaves on Helix aspersa

    Directory of Open Access Journals (Sweden)

    Fernanda R. da Silva

    2013-01-01

    Full Text Available Tobacco farmers are routinely exposed to complex mixtures of inorganic and organic chemicals present in tobacco leaves. In this study, we examined the genotoxicity of tobacco leaves in the snail Helix aspersa as a measure of the risk to human health. DNA damage was evaluated using the micronucleus test and the Comet assay and the concentration of cytochrome P450 enzymes was estimated. Two groups of snails were studied: one fed on tobacco leaves and one fed on lettuce (Lactuca sativa L leaves (control group. All of the snails received leaves (tobacco and lettuce leaves were the only food provided and water ad libitum. Hemolymph cells were collected after 0, 24, 48 and 72 h. The Comet assay and micronucleus test showed that exposure to tobacco leaves for different periods of time caused significant DNA damage. Inhibition of cytochrome P450 enzymes occurred only in the tobacco group. Chemical analysis indicated the presence of the alkaloid nicotine, coumarins, saponins, flavonoids and various metals. These results show that tobacco leaves are genotoxic in H. aspersa and inhibit cytochrome P450 activity, probably through the action of the complex chemical mixture present in the plant.

  19. Biomonitoring of genotoxic exposure among stainless steel welders

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Boisen, T; Christensen, J M

    1992-01-01

    A biosurvey in the Danish metal industry measured the genotoxic exposure from stainless steel welding. The study comprised measurements of chromosomal aberrations (CA), sister-chromatid exchanges (SCE), unscheduled DNA synthesis (UDS) in peripheral lymphocytes and serum immunoglobulin G. Environm......A biosurvey in the Danish metal industry measured the genotoxic exposure from stainless steel welding. The study comprised measurements of chromosomal aberrations (CA), sister-chromatid exchanges (SCE), unscheduled DNA synthesis (UDS) in peripheral lymphocytes and serum immunoglobulin G....... A higher frequency of chromosomal aberrations, classified as translocations, double minutes, exchanges and rings, was observed in stainless steel welders than in non-welders. SCE was lower in welders working with both MMA and TIG welding than in reference persons. N-Acetoxy-N-acetylaminofluorene (NA...... lymphocytes in exposed persons compared with non-exposed are suggested. MMA welding gave the highest exposure to chromium, an increased number of chromosomal aberrations and a decrease in SCE when compared with TIG welding. Consequently improvements in the occupational practice of stainless steel welding...

  20. Cytotoxicity and genotoxicity property of hydroxyapatite-mullite eluates.

    Science.gov (United States)

    Kalmodia, Sushma; Sharma, Vyom; Pandey, Alok K; Dhawan, Alok; Basu, Bikramjit

    2011-02-01

    Long-term biomedical applications of implant materials may cause osteolysis, aseptic losing and toxicity. Therefore, we investigated the cytotoxic and genotoxic potential of hydroxyapatite (HA) mullite eluates in L929 mouse fibroblast cells. The spark plasma sintered HA-20% mullite biocomposite (HA20M) were ground using mortar and pestle as well as ball milling. The cells were exposed for 6 h to varying concentrations (10, 25, 50, 75 and 100%) of the eluates of HA-20% mullite (87 nm), HA (171 nm) and mullite (154 nm). The scanning electron microscopy and MTT assay revealed the concentration dependent toxicity of H20M eluate at and above 50%. The analysis of the DNA damaging potential of HA, mullite and HA20M eluates using Comet assay demonstrated a significant DNA damage by HA20M which was largely related to the presence of mullite. The results collectively demonstrate the cytotoxic and genotoxic potential of HA20M eluate in L929 cells is dependent on particle size, concentration and composition.

  1. Antioxidant, genotoxic and antigenotoxic activities of daphne gnidium leaf extracts

    Directory of Open Access Journals (Sweden)

    Chaabane Fadwa

    2012-09-01

    Full Text Available Abstract Background Plants play a significant role in maintaining human health and improving the quality of human life. They serve humans well as valuable components of food, as well as in cosmetics, dyes, and medicines. In fact, many plant extracts prepared from plants have been shown to exert biological activity in vitro and in vivo. The present study explored antioxidant and antigenotoxic effects of Daphne gnidium leaf extracts. Methods The genotoxic potential of petroleum ether, chloroform, ethyl acetate, methanol and total oligomer flavonoid (TOF enriched extracts from leaves of Daphne gnidium, was assessed using Escherichia coli PQ37. Likewise, the antigenotoxicity of the same extracts was tested using the “SOS chromotest test”. Antioxidant activities were studied using non enzymatic and enzymatic method: NBT/Riboflavine and xantine oxidase. Results None of the different extracts produced a genotoxic effect, except TOF extract at the lowest tested dose. Our results showed that D. gnidium leaf extracts possess an antigenotoxic effect against the nitrofurantoin a mutagen of reference. Ethyl acetate and TOF extracts were the most effective in inhibiting xanthine oxidase activity. While, methanol extract was the most potent superoxide scavenger when tested with the NBT/Riboflavine assay. Conclusions The present study has demonstrated that D. gnidium leaf extract possess antioxidant and antigenotoxic effects. These activities could be ascribed to compounds like polyphenols and flavonoid. Further studies are required to isolate the active molecules.

  2. A review of the genotoxicity of trimethylolpropane triacrylate (TMPTA).

    Science.gov (United States)

    Kirkland, David; Fowler, Paul

    2018-04-01

    Trimethylolpropane triacrylate (TMPTA) is a trifunctional acrylate monomer which polymerizes rapidly when exposed to sources of free radicals. It is widely used as a reactive diluent and polymer building block in the formulation of overprint varnishes, inks and a variety of wood, plastic and metal coatings. TMPTA has been tested in a range of in vitro and in vivo genotoxicity tests. There is no clear evidence of induction of gene mutations by TMPTA in bacteria or mammalian cells in vitro, but there is evidence of clastogenicity from induction of small colony tk mutants in the mouse lymphoma assay, and also induction of micronuclei and chromosomal aberrations. However, TMPTA was negative in bone marrow or blood micronucleus tests in vivo following oral or repeated dermal application, and did not induce comets in bone marrow or liver of mice following intravenous administration, which would have achieved plasma (and therefore tissue) concentrations estimated to exceed those inducing clastogenic effects in vitro. It is concluded that TMPTA is not genotoxic in vivo. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Chapter 2. Surge capacity and infrastructure considerations for mass critical care. Recommendations and standard operating procedures for intensive care unit and hospital preparations for an influenza epidemic or mass disaster

    NARCIS (Netherlands)

    Hick, John L.; Christian, Michael D.; Sprung, Charles L.; Camargo, Ruben; Ceraso, Daniel; Azoulay, Elie; Duguet, Alexandre; Guery, Benoit; Reinhart, Konrad; Adini, Bruria; Barlavie, Yaron; Benin-Goren, Odeda; Cohen, Robert; Klein, Motti; Leoniv, Yuval; Margalit, Gila; Rubinovitch, Bina; Sonnenblick, Moshe; Steinberg, Avraham; Weissman, Charles; Wolff, Donna; Kesecioglu, Jozef; de Jong, Menno; Moreno, Rui; An, Youzhong; Du, Bin; Joynt, Gavin M.; Colvin, John; Loo, Shi; Richards, Guy; Artigas, Antonio; Pugin, Jerome; Amundson, Dennis; Devereaux, Asha; Beigel, John; Danis, Marion; Farmer, Chris; Maki, Dennis; Masur, Henry; Rubinson, Lewis; Sandrock, Christian; Talmor, Daniel; Truog, Robert; Zimmerman, Janice; Brett, Steve; Montgomery, Hugh; Rhodes, Andrew; Sanderson, Frances; Taylor, Bruce; Monrgomery, Hugh

    2010-01-01

    To provide recommendations and standard operating procedures for intensive care unit (ICU) and hospital preparations for a mass disaster or influenza epidemic with a specific focus on surge capacity and infrastructure considerations. Based on a literature review and expert opinion, a Delphi process

  4. Soil genotoxicity assessment: a new stategy based on biomolecular tools and plant bioindicators.

    Science.gov (United States)

    Citterio, Sandra; Aina, Roberta; Labra, Massimo; Ghiani, Alessandra; Fumagalli, Pietro; Sgorbati, Sergio; Santagostino, Angela

    2002-06-15

    The setting up of efficient early warning systems is a challenge to research for preventing environmental alteration and human disease. In this paper, we report the development and the field application of a new biomonitoring methodology for assessing soil genotoxicity. In the first part, the use of amplified fragment length polymorphism and flow cytometry techniques to detect DNA damage induced by soils artificially contaminated with heavy metals as potentially genotoxic compounds is explained. Results show that the combination of the two techniques leads to efficient detection of the sublethal genotoxic effect induced in the plant bioindicator by contaminated soil. By contrast, the classic mortality, root, and shoot growth vegetative endpoints prove inappropriate for assessing soil genotoxicity because, although they cause genotoxic damage, some heavy metals do not affect sentinel plant development negatively. The statistical elaboration of the data obtained led to the development of a statistical predictive model which differentiates four different levels of soil genotoxic pollution and can be used everywhere. The second part deals with the application of the biomonitoring protocol in the genotoxic assessment of two areas surrounding a steelworks in northern Italy and the effectiveness of this methodology. In this particular case, in these areas, the predictive model reveals a pollution level strictly correlated to the heavy metal concentrations revealed by traditional chemical analysis.

  5. Protective Effect of Curcumin against Ionizing Radiation (IR)-induced Cytotoxicity and Genotoxicity in HepG2 Cells

    International Nuclear Information System (INIS)

    Chung, Dong Min; Nasir Uddin, S. M.; Ryu, Tae Ho; Kang, Mi Young; Kim, Jin Kyu

    2013-01-01

    Ionizing radiation (IR) has many practical applications such as medicine, foods, agricultures, industries, and research laboratories. However, the increasing use of radiation is associated with radiation accidents threatening human health. It is well known that exposure to IR gives rise to genomic alterations, mutagenesis, and cell death. IR is absorbed directly by DNA, leading to various DNA damages (single or double-strand breaks, base damage, and DNA-DNA or DNA-protein cross-linkages) in many living organisms. Therefore, the development of effective and nontoxic radioprotective agents is of considerable interest. Curcumin (C 12 H 20 O 6 , structure is the major yellow component of Curcuma longa with biological activities (antioxidant, anti-proliferative and anti-inflammatory properties). It has been widely used as food and medicine for a long time. The aim of our present study is to investigate the protective effects of curcumin against IR-induced cytotoxicity and genotoxicity in cultured HepG2 cells

  6. New investigations into the genotoxicity of cobalt compounds and their impact on overall assessment of genotoxic risk.

    Science.gov (United States)

    Kirkland, David; Brock, Tom; Haddouk, Hasnaà; Hargeaves, Victoria; Lloyd, Melvyn; Mc Garry, Sarah; Proudlock, Raymond; Sarlang, Séverine; Sewald, Katherina; Sire, Guillaume; Sokolowski, Andrea; Ziemann, Christina

    2015-10-01

    The genotoxicity of cobalt metal and cobalt compounds has been widely studied. Several publications show induction of chromosomal aberrations, micronuclei or DNA damage in mammalian cells in vitro in the absence of S9. Mixed results were seen in gene mutation studies in bacteria and mammalian cells in vitro, and in chromosomal aberration or micronucleus assays in vivo. To resolve these inconsistencies, new studies were performed with soluble and poorly soluble cobalt compounds according to OECD-recommended protocols. Induction of chromosomal damage was confirmed in vitro, but data suggest this may be due to oxidative stress. No biologically significant mutagenic responses were obtained in bacteria, Tk(+/-) or Hprt mutation tests. Negative results were also obtained for chromosomal aberrations (in bone marrow and spermatogonia) and micronuclei at maximum tolerated doses in vivo. Poorly soluble cobalt compounds do not appear to be genotoxic. Soluble compounds do induce some DNA and chromosomal damage in vitro, probably due to reactive oxygen. The absence of chromosome damage in robust GLP studies in vivo suggests that effective protective processes are sufficient to prevent oxidative DNA damage in whole mammals. Overall, there is no evidence of genetic toxicity with relevance for humans of cobalt substances and cobalt metal. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  7. CriticalEd

    DEFF Research Database (Denmark)

    Kjellberg, Caspar Mølholt; Meredith, David

    2014-01-01

    . Since the comments are not input sequentially, with regard to position, but in arbitrary order, this list must be sorted by copy/pasting the rows into place—an error-prone and time-consuming process. Scholars who produce critical editions typically use off-the-shelf music notation software......The best text method is commonly applied among music scholars engaged in producing critical editions. In this method, a comment list is compiled, consisting of variant readings and editorial emendations. This list is maintained by inserting the comments into a document as the changes are made......, consisting of a Sibelius plug-in, a cross-platform application, called CriticalEd, and a REST-based solution, which handles data storage/retrieval. A prototype has been tested at the Danish Centre for Music Publication, and the results suggest that the system could greatly improve the efficiency...

  8. Evaluation of the tickcide, genotoxic, and mutagenic effects of the Ruta graveolens L. (Rutaceae

    Directory of Open Access Journals (Sweden)

    Alessandra Vargas de Carvalho

    2015-10-01

    Full Text Available Current analysis investigated the tickcide effects of the aqueous extract and chloroform fractions of Ruta graveolens L. (rue on engorged females of Rhipicephalus microplus, as well as their genotoxic and mutagenic effects on human leukocytes. The best tickcide activity (non-dependent dose and genotoxic / mutagenic effects (dependent-dose were observed on exposure to chloroform fractions. Results suggest that extract fractions of R. graveolens L are efficient against R. microplus, although the fraction and the tested concentrations show genotoxic and mutagenic potential for human leukocytes.

  9. Acute Toxicity and Genotoxic Activity of Avocado Seed Extract (Persea americana Mill., c.v. Hass

    Directory of Open Access Journals (Sweden)

    Eduardo Padilla-Camberos

    2013-01-01

    Full Text Available The use of vegetal extracts requires toxicological and genotoxic evaluations to establish and verify safety before being added to human cosmetic, pharmaceutical medicine, or alimentary products. Persea americana seeds have been used in traditional medicine as treatment for several diseases. In this work, the ethanolic seed extract of Persea americana was evaluated with respect to its genotoxic potential through micronucleus assay in rodents. The frequency of micronuclei in groups of animals treated with avocado seed extract showed no differences compared to the negative control (vehicle; therefore, it is considered that the avocado seed extract showed no genotoxic activity in the micronucleus test.

  10. Acute toxicity and genotoxic activity of avocado seed extract (Persea americana Mill., c.v. Hass).

    Science.gov (United States)

    Padilla-Camberos, Eduardo; Martínez-Velázquez, Moisés; Flores-Fernández, José Miguel; Villanueva-Rodríguez, Socorro

    2013-01-01

    The use of vegetal extracts requires toxicological and genotoxic evaluations to establish and verify safety before being added to human cosmetic, pharmaceutical medicine, or alimentary products. Persea americana seeds have been used in traditional medicine as treatment for several diseases. In this work, the ethanolic seed extract of Persea americana was evaluated with respect to its genotoxic potential through micronucleus assay in rodents. The frequency of micronuclei in groups of animals treated with avocado seed extract showed no differences compared to the negative control (vehicle); therefore, it is considered that the avocado seed extract showed no genotoxic activity in the micronucleus test.

  11. Genotoxic damage in pathology anatomy laboratory workers exposed to formaldehyde

    International Nuclear Information System (INIS)

    Costa, Solange; Coelho, Patricia; Costa, Carla; Silva, Susana; Mayan, Olga; Silva Santos, Luis; Gaspar, Jorge; Teixeira, Joao Paulo

    2008-01-01

    Formaldehyde (FA) is a chemical traditionally used in pathology and anatomy laboratories as a tissue preservative. Several epidemiological studies of occupational exposure to FA have indicated an increased risk of nasopharyngeal cancers in industrial workers, embalmers and pathology anatomists. There is also a clear evidence of nasal squamous cell carcinomas from inhalation studies in the rat. The postulated mode of action for nasal tumours in rats was considered biologically plausible and considered likely to be relevant to humans. Based on the available data IARC, the International Agency for Research on Cancer, has recently classified FA as a human carcinogen. Although the in vitro genotoxic as well as the in vivo carcinogenic potentials of FA are well documented in mammalian cells and in rodents, evidence for genotoxic effects and carcinogenic properties in humans is insufficient and conflicting thus remains to be more documented. To evaluate the genetic effects of long-term occupational exposure to FA a group of 30 Pathological Anatomy laboratory workers was tested for a variety of biological endpoints, cytogenetic tests (micronuclei, MN; sister chromatid exchange, SCE) and comet assay. The level of exposure to FA was evaluated near the breathing zone of workers, time weighted average of exposure was calculated for each subject. The association between the biomarkers and polymorphic genes of xenobiotic metabolising and DNA repair enzymes was also assessed. The mean level of exposure was 0.44 ± 0.08 ppm (0.04-1.58 ppm). MN frequency was significantly higher (p = 0.003) in the exposed subjects (5.47 ± 0.76) when compared with controls (3.27 ± 0.69). SCE mean value was significantly higher (p < 0.05) among the exposed group (6.13 ± 0.29) compared with control group (4.49 ± 0.16). Comet assay data showed a significant increase (p < 0.05) of TL in FA-exposed workers (60.00 ± 2.31) with respect to the control group (41.85 ± 1.97). A positive correlation was

  12. Dietary modulation of the biotransformation and genotoxicity of aflatoxin B1

    International Nuclear Information System (INIS)

    Gross-Steinmeyer, Kerstin; Eaton, David L.

    2012-01-01

    Diet and its various components are consistently identified as among the most important ‘risk factors’ for cancer worldwide, yet great uncertainty remains regarding the relative contribution of nutritive (e.g., vitamins, calories) vs. non-nutritive (e.g., phytochemicals, fiber, contaminants) factors in both cancer induction and cancer prevention. Among the most potent known human dietary carcinogens is the mycotoxin, aflatoxin B 1 (AFB). AFB and related aflatoxins are produced as secondary metabolites by the molds Aspergillus flavus and Aspergillus parasiticus that commonly infect poorly stored foods including peanuts, pistachios, corn, and rice. AFB is a potent hepatocarcinogenic agent in numerous animal species, and has been implicated in the etiology of human hepatocellular carcinoma. Recent research has shown that many diet-derived factors have great potential to influence AFB biotransformation, and some efficiently protect from AFB-induced genotoxicity. One key mode of action for reducing AFB-induced carcinogenesis in experimental animals was shown to be the induction of detoxification enzymes such as certain glutathione-S-transferases that are regulated through the Keap1–Nrf2–ARE signaling pathway. Although initial studies utilized the dithiolthione drug, oltipraz, as a prototypical inducer of antioxidant response, dietary components such as suforaphane (SFN) are also effective inducers of this pathway in rodent models. However, human GSTs in general do not appear to be extensively induced by SFN, and GSTM1 – the only human GST with measurable catalytic activity toward aflatoxin B 1 -8,9-epoxide (AFBO; the genotoxic metabolite of AFB), does not appear to be induced by SFN, at least in human hepatocytes, even though its expression in human liver cells does appear to offer considerable protection against AFB–DNA damage. Although induction of detoxification pathways has served as the primary mechanistic focus of chemoprevention studies, protective

  13. Can the comet assay be used reliably to detect nanoparticle-induced genotoxicity?

    Science.gov (United States)

    Karlsson, Hanna L; Di Bucchianico, Sebastiano; Collins, Andrew R; Dusinska, Maria

    2015-03-01

    The comet assay is a sensitive method to detect DNA strand breaks as well as oxidatively damaged DNA at the level of single cells. Today the assay is commonly used in nano-genotoxicology. In this review we critically discuss possible interactions between nanoparticles (NPs) and the comet assay. Concerns for such interactions have arisen from the occasional observation of NPs in the "comet head", which implies that NPs may be present while the assay is being performed. This could give rise to false positive or false negative results, depending on the type of comet assay endpoint and NP. For most NPs, an interaction that substantially impacts the comet assay results is unlikely. For photocatalytically active NPs such as TiO2 , on the other hand, exposure to light containing UV can lead to increased DNA damage. Samples should therefore not be exposed to such light. By comparing studies in which both the comet assay and the micronucleus assay have been used, a good consistency between the assays was found in general (69%); consistency was even higher when excluding studies on TiO2 NPs (81%). The strong consistency between the comet and micronucleus assays for a range of different NPs-even though the two tests measure different endpoints-implies that both can be trusted in assessing the genotoxicity of NPs, and that both could be useful in a standard battery of test methods. © 2014 Wiley Periodicals, Inc.

  14. Inhibition of TGFbeta1 Signaling Attenutates ATM Activity inResponse to Genotoxic Stress

    Energy Technology Data Exchange (ETDEWEB)

    Kirshner, Julia; Jobling, Michael F.; Pajares, Maria Jose; Ravani, Shraddha A.; Glick, Adam B.; Lavin, Martin J.; Koslov, Sergei; Shiloh, Yosef; Barcellos-Hoff, Mary Helen

    2006-09-15

    Ionizing radiation causes DNA damage that elicits a cellular program of damage control coordinated by the kinase activity of ataxia telangiectasia mutated protein (ATM). Transforming growth factor {beta}1 (TGF{beta}), which is activated by radiation, is a potent and pleiotropic mediator of physiological and pathological processes. Here we show that TGF{beta} inhibition impedes the canonical cellular DNA damage stress response. Irradiated Tgf{beta}1 null murine epithelial cells or human epithelial cells treated with a small molecule inhibitor of TGF{beta} type I receptor kinase exhibit decreased phosphorylation of Chk2, Rad17 and p53, reduced {gamma}H2AX radiation-induced foci, and increased radiosensitivity compared to TGF{beta} competent cells. We determined that loss of TGF{beta} signaling in epithelial cells truncated ATM autophosphorylation and significantly reduced its kinase activity, without affecting protein abundance. Addition of TGF{beta} restored functional ATM and downstream DNA damage responses. These data reveal a heretofore undetected critical link between the microenvironment and ATM that directs epithelial cell stress responses, cell fate and tissue integrity. Thus, TGF{beta}1, in addition to its role in homoeostatic growth control, plays a complex role in regulating responses to genotoxic stress, the failure of which would contribute to the development of cancer; conversely, inhibiting TGF{beta} may be used to advantage in cancer therapy.

  15. Genotoxic Biomarkers in Erythrocytes of Lepidochelys olivacea (Cheloniidae from Colombia

    Directory of Open Access Journals (Sweden)

    Victor Hugo Quiroz Herrera

    2017-09-01

    Full Text Available This research was conducted in the municipality of Bahia Solano, Colombia, and had as a goal to detect damage erythrocytes circulating with nuclear lesions in fifty-five Olive Ridley adult females using acridine orange immunostain, and correlate its frequencies with some physiological and biometric parameters. We determine a micronucleated erythrocytes (MNE frequency of 0.6 ± 0.6 and nuclear buds (NBE of 2.1 ± 1.9. We not found any relationship between the nuclear lesions with physiological or biometric parameters evaluated (Pearson and Kruskal-Wallis, p<0.05. We define a significative statistical difference (p=0.035 between both nuclear lesions frequencies. This results show nuclear damages in erythrocytes of Olive Ridley sea turtle for the first time in Colombia as an outcome of genotoxic stress. Also contributes key information for future research in the ecotoxicology area for endangered marine species.

  16. The potential for new methods to assess human reproductive genotoxicity

    International Nuclear Information System (INIS)

    Mendelsohn, M.L.

    1987-09-01

    The immediate prospects are not good for practical methods for measuring the human heritable mutation rate. The methods discussed here range from speculative to impractical, and at best are sensitive enough only for large numbers of subjects. Given the rapid development of DNA methods and the current status of two-dimensional gel electrophoresis, there is some hope that the intermediate prospects may be better. In contrast, the prospects for useful cellular-based male germinal methods seem more promising and immediate. Effective specific locus methods for sperm are already conceivable and may be practical in a few years. Obviously such methods will not predict heritable effects definitively, but they will provide direct information on reproductive genotoxicity and should contribute significantly to many current medical and environmental situations where genetic damage is suspected. 22 refs

  17. Genotoxicity and potential carcinogenicity of cyanobacterial toxins - a review.

    Science.gov (United States)

    Zegura, Bojana; Straser, Alja; Filipič, Metka

    2011-01-01

    The occurrence of cyanobacterial blooms has increased significantly in many regions of the world in the last century due to water eutrophication. These blooms are hazardous to humans, animals, and plants due to the production of cyanotoxins, which can be classified in five different groups: hepatotoxins, neurotoxins, cytotoxins, dermatotoxins, and irritant toxins (lipopolysaccharides). There is evidence that certain cyanobacterial toxins are genotoxic and carcinogenic; however, the mechanisms of their potential carcinogenicity are not well understood. The most frequently occurring and widespread cyanotoxins in brackish and freshwater blooms are the cyclic heptapeptides, i.e., microcystins (MCs), and the pentapeptides, i.e., nodularins (NODs). The main mechanism associated with potential carcinogenic activity of MCs and NOD is the inhibition of protein phosphatases, which leads to the hyperphosphorylation of cellular proteins, which is considered to be associated with their tumor-promoting activity. Apart from this, MCs and NOD induce increased formation of reactive oxygen species and, consequently, oxidative DNA damage. There is also evidence that MCs and NOD induce micronuclei, and NOD was shown to have aneugenic activity. Both cyanotoxins interfere with DNA damage repair pathways, which, along with DNA damage, is an important factor involved in the carcinogenicity of these agents. Furthermore, these toxins increase the expression of TNF-α and early-response genes, including proto-oncogenes, genes involved in the response to DNA damage, cell cycle arrest, and apoptosis. Rodent studies indicate that MCs and NOD are tumor promotors, whereas NOD is thought to have also tumor-initiating activity. Another cyanobacterial toxin, cylindrospermopsin (CYN), which has been neglected for a long time, is lately being increasingly found in the freshwater environment. The principal mechanism of its toxicity is the irreversible inhibition of protein synthesis. It is pro-genotoxic

  18. Urinary screening for potentially genotoxic exposures in a chemical industry

    Energy Technology Data Exchange (ETDEWEB)

    Ahlborg, G. Jr.; Bergstroem, B.H.; Hogstedt, C.; Einistoe, P.S.; Sorsa, M.

    1985-10-01

    Mutagenic activity, measured by the bacterial fluctuation assay and thioether concentration in urine from workers at a chemical plant producing pharmaceuticals and explosives, was determined before and after exposure. Of 12 groups only those exposed to trinitrotoluene (n = 14) showed a significant increase in mutagenic activity using Salmonella typhimurium TA 98 without any exogenous metabolic system. The same strain responded only weakly when the S-9 mix was used; with Escherichia coli WP2 uvrA no effect of exposure was observed. Urinary thioether concentration was higher among smokers than among non-smokers, but occupational exposure had no effect. Urinary mutagenicity testing may be a useful tool for screening potentially genotoxic exposures in complex chemical environments.

  19. Effects of wood dust:Inflammation, Genotoxicity and Cancer

    DEFF Research Database (Denmark)

    Lange, Jette Bornholdt

    cell line A549 measuring inflammatory and DNA damaging effects. The second part consists of a molecular analysis of the K-ras gene for mutations in the hotspots codons in human sinonasal cancers. Design, calibration and validation of the assays were performed. Cancer at the sinonasal cavities is rare...... with incidence rates between of 0.3 to 1.4 per 100,000 for men and 0.1 to 0.8 per 100,000 for women in Europe, depending on country. However, cancer at this site is associated with occupational exposures including wood dust. Especially the adenocarcinoma subtype is strongly associated with exposure to wood dust...... and their potential to cause DNA damage. Contrary to our hypothesis, we showed that pure wood dust is able to cause primary DNA damage, independent of inflammation as well as hardwoods had no higher inflammatory or genotoxic potential than softwoods. To investigate the molecular mechanisms behind the wood dust...

  20. Comet Assay on Daphnia magna in eco-genotoxicity testing.

    Science.gov (United States)

    Pellegri, Valerio; Gorbi, Gessica; Buschini, Annamaria

    2014-10-01

    Detection of potentially hazardous compounds in water bodies is a priority in environmental risk assessment. For the evaluation and monitoring of water quality, a series of methodologies may be applied. Among them, the worldwide used toxicity tests with organisms of the genus Daphnia is one of the most powerful. In recent years, some attempts were made to utilize Daphnia magna in genotoxicity testing as many of the new environmental contaminants are described as DNA-damaging agents in aquatic organisms. The aim of this research was to develop a highly standardized protocol of the Comet Assay adapted for D. magna, especially regarding the isolation of cells derived from the same tissue (haemolymph) from newborn organisms exposed in vivo. Several methods for haemolymph extraction and different Comet Assay parameters were compared. Electrophoretic conditions were adapted in order to obtain minimum DNA migration in cells derived from untreated organisms and, at the same time, maximum sensitivity in specimens treated with known genotoxicants (CdCl2 and H2O2). Additional tests were performed to investigate if life-history traits of the cladoceran (such as the age of adult organisms that provide newborns, the clutch size of origin, the number of generations reared in standard conditions) and the water composition as well, might influence the response of the assay. This study confirms the potential application of the Comet Assay in D. magna for assessing genotoxic loads in aqueous solution. The newly developed protocol could integrate the acute toxicity bioassay, thus expanding the possibility of using this model species in freshwater monitoring (waters, sediment and soil elutriates) and is in line with the spirit of the EU Water Framework Directive in reducing the number of bioassays that involve medium-sized species. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Genotoxicity profile of erinacine A-enriched Hericium erinaceus mycelium

    Directory of Open Access Journals (Sweden)

    I-Chen Li

    2014-01-01

    Full Text Available Hericium erinaceus (H. erinaceus has a long history of usage in traditional Chinese medicine for the treatment of gastric disorders. Recently, it has become a well-established candidate in causing positive brain and nerve health-related activities by inducing nerve growth factor (NGF from its bioactive ingredient, erinacine A. This active compound, which exists only in fermented mycelium but not in its fruiting body, increases NGF levels in astroglial cells in vitro as well as catecholamine and NGF levels in vivo. With increasing recognition of erinacine A in H. erinaceus (EAHE mycelium improving neurodegenerative diseases, numerous products are being marketed based on these functional claims. To our knowledge, there have been no reports on the mutagenicity of EAHE prior to this paper. Hence, the present study was undertaken to determine the mutagenicity and genotoxicity effects of EAHE mycelium conducted in three standard battery of tests (reverse mutation, chromosomal aberration, and micronuclei tests according to the latest guidelines in order to meet all international regulatory requirements and provide information on the safety of this new and promising natural remedy. Our results have indicated that EAHE mycelium did not significantly increase the number of revertant colonies in the bacterial reverse mutation test nor induce higher frequency of aberrations in the chromosome aberration test. Moreover, no statistically significant EAHE mycelium-related increase was observed in the incidence of reticulocytes per 1000 red blood cells and micronucleated reticulocytes per 1000 reticulocytes. In conclusion, the three standard battery of tests suggested that EAHE mycelium was devoid of mutagenicity and genotoxicity in the tested doses and experimental conditions.

  2. Pb low doses induced genotoxicity in Lactuca sativa plants.

    Science.gov (United States)

    Silva, S; Silva, P; Oliveira, H; Gaivão, I; Matos, M; Pinto-Carnide, O; Santos, C

    2017-03-01

    Soil and water contamination by lead (Pb) remains a topic of great concern, particularly regarding crop production. The admissible Pb values in irrigation water in several countries range from ≈0.1 to ≈5 mg L -1 . In order to evaluate putative effects of Pb within legal doses on crops growth, we exposed Lactuca sativa seeds and seedlings to increasing doses of Pb(NO 3 ) 2 up to 20 mg L -1 . The OECD parameter seed germination and seedling/plant growth were not affected by any of the Pb-concentrations used. However, for doses higher than 5 mg L -1 significant DNA damage was detected: Comet assay detected DNA fragmentation at ≥ 5 mg L -1 and presence of micronuclei (MN) were detected for 20 mg L -1 . Also, cell cycle impairment was observed for doses as low as 0.05 mg L -1 and 0.5 mg L -1 (mostly G 2 arrest). Our data show that for the low doses of Pb used, the OECD endpoints were not able to detect toxicity, while more sensitive endpoints (related with DNA damage and mitotic/interphase disorders) identified genotoxic and cytostatic effects. Furthermore, the nature of the genotoxic effect was dependent on the concentration. Finally, we recommend that MN test and the comet assay should be included as sensitive endpoints in (eco)toxicological assays. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Genotoxicity profile of erinacine A-enriched Hericium erinaceus mycelium.

    Science.gov (United States)

    Li, I-Chen; Chen, Yen-Lien; Chen, Wan-Ping; Lee, Li-Ya; Tsai, Yueh-Ting; Chen, Chin-Chu; Chen, Chin-Shuh

    2014-01-01

    Hericium erinaceus ( H. erinaceus ) has a long history of usage in traditional Chinese medicine for the treatment of gastric disorders. Recently, it has become a well-established candidate in causing positive brain and nerve health-related activities by inducing nerve growth factor (NGF) from its bioactive ingredient, erinacine A. This active compound, which exists only in fermented mycelium but not in its fruiting body, increases NGF levels in astroglial cells in vitro as well as catecholamine and NGF levels in vivo . With increasing recognition of erinacine A in H. erinaceus (EAHE) mycelium improving neurodegenerative diseases, numerous products are being marketed based on these functional claims. To our knowledge, there have been no reports on the mutagenicity of EAHE prior to this paper. Hence, the present study was undertaken to determine the mutagenicity and genotoxicity effects of EAHE mycelium conducted in three standard battery of tests (reverse mutation, chromosomal aberration, and micronuclei tests) according to the latest guidelines in order to meet all international regulatory requirements and provide information on the safety of this new and promising natural remedy. Our results have indicated that EAHE mycelium did not significantly increase the number of revertant colonies in the bacterial reverse mutation test nor induce higher frequency of aberrations in the chromosome aberration test. Moreover, no statistically significant EAHE mycelium-related increase was observed in the incidence of reticulocytes per 1000 red blood cells and micronucleated reticulocytes per 1000 reticulocytes. In conclusion, the three standard battery of tests suggested that EAHE mycelium was devoid of mutagenicity and genotoxicity in the tested doses and experimental conditions.

  4. Molecular and cytogenetic evaluation for potential genotoxicity of hydrocortisone

    Directory of Open Access Journals (Sweden)

    Maha Aly Fahmy

    2015-09-01

    Full Text Available Objective: To assess the risk of hydrocortisone sodium succinate through different end points of genotoxicity. Methods: The study examined the induction of chromosomal aberrations in bone marrow cells, morphological sperm abnormalities, the effect on dominant lethal gene and protein synthesis. Hydrocortisone was given intraperitoneally at three dose levels 26, 39 and 52 mg/kg body weight which was equivalent to the therapeutic doses in man. Results: The results showed that single dose treatment with different doses had no effect on chromosomal aberrations. The dose of 52 mg/kg body weight induced significant percentage of chromosomal aberrations in bone marrow cells after repeated treatment for 7 and 14 days. Significant effect of morphological sperm abnormalities was demonstrated only after treatment with the dose of 52 mg/kg body weight. For examining the dominant lethal mutation, male mice were injected with dose of 39 mg/kg body weight for 5 consecutive days. Mating between treated males and virgin untreated females were performed at different time intervals. The results showed that the percentage of fertile mating at 1–7 and 8–14 days reduced to 50% and 60% respectively compared with control group while no effect was recorded at 15–21 days. The percentage of dominant lethal mutation reached 0.32%, 4.4% and 0% in mating intervals respectively indicating pronounced effect of hydrocortisone at the interval 8–14 days which represented by the late spermatids. The results also showed that the repeated treatment with the dose of 52 mg/kg body weight inhibited protein synthesis which contributed to the cytotoxic effect of the drug. Conclusions: It is concluded that long term treatment with large doses of hydrocortisone may have genotoxic effect.

  5. Development of a Transgenic Model to Assess Bioavailable Genotoxicity in Sediments

    National Research Council Canada - National Science Library

    1999-01-01

    This technical note describes the rationale for using transgenic animal models to assess the potential genotoxicity of sediments, the benefits that can be obtained using such models versus currently...

  6. Genotoxic evaluation of an industrial effluent from an oil refinery using plant and animal bioassays

    Directory of Open Access Journals (Sweden)

    Fernando Postalli Rodrigues

    2010-01-01

    Full Text Available Polycyclic aromatic hydrocarbons (PAHs are genotoxic chemicals commonly found in effluents from oil refineries. Bioassays using plants and cells cultures can be employed for assessing environmental safety and potential genotoxicity. In this study, the genotoxic potential of an oil refinery effluent was analyzed by means of micronucleus (MN testing of Alium cepa, which revealed no effect after 24 h of treatment. On the other hand, primary lesions in the DNA of rat (Rattus norvegicus hepatoma cells (HTC were observed through comet assaying after only 2 h of exposure. On considering the capacity to detect DNA damage of a different nature and of these cells to metabolize xenobiotics, we suggest the association of the two bioassays with these cell types, plant (Allium cepa and mammal (HTC cells, for more accurately assessing genotoxicity in environmental samples.

  7. Genotoxic evaluation of an industrial effluent from an oil refinery using plant and animal bioassays.

    Science.gov (United States)

    Rodrigues, Fernando Postalli; Angeli, José Pedro Friedmann; Mantovani, Mário Sérgio; Guedes, Carmen Luisa Barbosa; Jordão, Berenice Quinzani

    2010-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are genotoxic chemicals commonly found in effluents from oil refineries. Bioassays using plants and cells cultures can be employed for assessing environmental safety and potential genotoxicity. In this study, the genotoxic potential of an oil refinery effluent was analyzed by means of micronucleus (MN) testing of Alium cepa, which revealed no effect after 24 h of treatment. On the other hand, primary lesions in the DNA of rat (Rattus norvegicus) hepatoma cells (HTC) were observed through comet assaying after only 2 h of exposure. On considering the capacity to detect DNA damage of a different nature and of these cells to metabolize xenobiotics, we suggest the association of the two bioassays with these cell types, plant (Allium cepa) and mammal (HTC) cells, for more accurately assessing genotoxicity in environmental samples.

  8. Genotoxicity and ELF-magnetic fields: a review through the micronucleus assay

    International Nuclear Information System (INIS)

    Alcaraz, M.; Andreu-Galvez, M.; Sanchez-Villalobos, J. M.; Achel, D. G.; Olmos, E.; Martinez-Hernandez, C. M.

    2012-01-01

    Thirty for (34) published studies, conducted from 1994 to the present to evaluate the genotoxic effect of magnetic fields using ELF-EMF and diagnostic resonance on humans by the micronucleus assay have been reviewed. some characteristics of the assay methods, their significance to genotoxicity and basic interpretations of the results of these assays are discussed. of the studies analysed 70.5% implicated genotoxic effects induced by these magnetic fields: 52.9% were due to exposure to magnetic fields only and 17,6% by exposure to magnetic fields in combination with some treatment types, resulting in additive or synergistic effect. Evidence exist to support the notion that exposure of humans to magnetic fields stimulates genotoxic effects, although the actual mechanisms of action or even the true human health consequences resulting from these exposure still remain unclear. (Author) 80 refs.

  9. Measurement of DNA strand breaks as a biomarker of genotoxic pollutants

    Digital Repository Service at National Institute of Oceanography (India)

    Sarkar, A.; Patil, S.S.; Holkar, P.K.R.

    This paper deals with the development of a molecular biomarker technique by measurement of DNA integrity in marine organisms for biomonitoring of pollution due to genotoxic compounds. The marine environment is continuously being polluted...

  10. Genotoxicity Biomonitoring Along a Coastal Zone Under Influence of Offshore Petroleum Exploration (Southeastern Brazil).

    Science.gov (United States)

    Gutiérrez, Juan Manuel; da Conceição, Moisés Basilio; Molisani, Mauricio Mussi; Weber, Laura Isabel

    2018-03-01

    Offshore oil exploration creates threats to coastal ecosystems, including increasing urbanization and associated effluent releases. Genotoxicity biomarkers in mussels were determined across a gradient of coastal zone influences of offshore petroleum exploration in southeastern Brazil. Coastal ecosystems such as estuaries, beaches and islands were seasonally monitored for genotoxicity evaluation using the brown mussel Perna perna. The greatest DNA damage (5.2% ± 1.9% tail DNA and 1.5‰  ± 0.8‰ MN) were observed in urban estuaries, while Santana Archipelago showed levels of genotoxicity near zero and is considered a reference site. Mussels from urban and pristine beaches showed intermediate damage levels, but were also influenced by urbanization. Thus, mussel genotoxicity biomarkers greatly indicated the proposed oil exploration and urbanization scenarios that consequently are genetically affecting coastal organisms.

  11. Acute toxicity and genotoxicity of fermented traditional medicine oyaksungi-san

    Directory of Open Access Journals (Sweden)

    Hwayong Park

    2017-06-01

    Conclusion: As a whole, no acute toxicity or genotoxicity were observed in all the assays examined. Therefore, fermented OY is considered to be a safe material that can be used for development of complementary and alternative medicine using bioconversion.

  12. Genotoxic effects of boric acid and borax in zebrafish, Danio rerio using alkaline comet assay.

    Science.gov (United States)

    Gülsoy, Nagihan; Yavas, Cüneyd; Mutlu, Özal

    2015-01-01

    The present study is conducted to determine the potential mechanisms of Boron compounds, boric acid (BA) and borax (BX), on genotoxicity of zebrafish Danio rerio for 24, 48, 72 and 96-hours acute exposure (level:1, 4, 16, 64 mg/l BA and BX) in semi-static bioassay experiment. For that purpose, peripheral erythrocytes were drawn from caudal vein and Comet assay was applied to assess genotoxicity. Acute (96 hours) exposure and high concentrations of boric acid and borax increases % tail DNA and Olive tail moment. Genotoxicity was found for BA as concentration-dependent and BX as concentration and time dependent manner. In general, significant effects (P borax-induced genotoxicity in fish.

  13. The influence of abiotic factors present in the Rio de la Plata over the chromium genotoxicity

    International Nuclear Information System (INIS)

    Lopez, L.C.; Moretton, J.

    1997-01-01

    The alterations suffered by the well-known environmental genotoxic agent, Cr(V I), were studied. Cr(V I) salts were dissolved in water effluent river receptors waters such as from the Rio de la Plata. The influence of abiotic factors present in this kind of water was evaluated using the Rec. assay in Bacillus subtilis. The results detected a soluble fraction that potentiated Cr(V I) genotoxicity. This substance (or group of substances) is sensible to sterilization by heat and UV radiation, and its activity seems to decrease with particulate matter. Its genotoxicity was not affected by high concentrations of particulate matter in the Rio de la Plata water. In samples where chromium salts were added to raw river water, abiotic interference due to sterilization process occurred. A decrease in genotoxicity was found after filtration through inorganic filters (0.22 μ m) and an increase was noticed after exposure to UV radiation. (Author)

  14. COMPARATIVE GENOTOXIC RESPONSES TO ARSENITE IN GUINEA PIG, MOUSE, RAT AND HUMAN LYMPHOCYTES

    Science.gov (United States)

    Comparative genotoxic responses to arsenite in guinea pig, mouse, rat and human lymphocytes.Inorganic arsenic is a known human carcinogen causing skin, lung, and bladder cancer following chronic exposures. Yet, long-term laboratory animal carcinogenicity studies have ...

  15. Genotoxic Effects of Titanium Dioxide and Cerium Dioxide Nanoparticles in Human Respiratory Epithelial Cells

    Science.gov (United States)

    The nanomaterial industry has recently seen rapid growth, therefore, the risk assessment of human exposure to nanomaterials in consumer products is of paramount importance. The genotoxicity of nanomaterials is a fundamental aspect of hazard identification and regulatory guidance....

  16. The Genotoxicity of Titanium Dioxide and Cerium Dioxide Nanoparticles in Human Respiratory Epithelial Cells

    Science.gov (United States)

    Due to the exponential growth of the nanomaterial industry, risk assessment of human exposure to nanomaterials in consumer products is of paramount importance. The genotoxicity of nanomaterials is an important aspect of hazard identification and regulatory guidance. However, this...

  17. Genotoxic Effects of Exposure to Gasoline Fumes on Petrol Pump Workers

    OpenAIRE

    Amrin Shaikh; Darshana Barot; Divya Chandel

    2018-01-01

    Background: Petrol pump workers are occupationally exposed to gasoline and its fumes consisting of several mutagenic chemicals. Objective: To evaluate the genotoxic effects of exposure to gasoline fumes on petrol pump workers. Methods: The study groups included 70 petrol pump workers (exposed group) and 70 healthy age-matched individuals with no known exposure (comparison group). Buccal micronucleus cytome assay (BMCyt) was performed to check the genotoxicity caused due to inhalation ...

  18. Genotoxicity assessment data for exfoliated buccal cells exposed to mobile phone radiation

    Directory of Open Access Journals (Sweden)

    F.M. de Oliveira

    2017-12-01

    Full Text Available Healthy mobile phone users aged 18–30 y.o. provided exfoliated buccal cells samples from the right and left inner cheeks. A total of 2000 cells per subject were screened for the presence of micronuclei as a sign of genotoxic damage, according to the mobile phone use profile of each user. Keywords: Electromagnetic fields, Mobile phones, Genotoxicity, Micronuclei, Exfoliated buccal cells, Feulgen stain

  19. The use of ex vivo human skin tissue for genotoxicity testing

    International Nuclear Information System (INIS)

    Reus, Astrid A.; Usta, Mustafa; Krul, Cyrille A.M.

    2012-01-01

    As a result of the chemical legislation concerning the registration, evaluation, authorization and restriction of chemicals (REACH), and the Seventh Amendment to the Cosmetics Directive, which prohibits animal testing in Europe for cosmetics, alternative methods for safety evaluation of chemicals are urgently needed. Current in vitro genotoxicity assays are not sufficiently predictive for the in vivo situation, resulting in an unacceptably high number of misleading positives. For many chemicals and ingredients of personal care products the skin is the first site of contact, but there are no in vitro genotoxicity assays available in the skin for additional evaluation of positive or equivocal responses observed in regulatory in vitro genotoxicity assays. In the present study ex vivo human skin tissue obtained from surgery was used for genotoxicity evaluation of chemicals by using the comet assay. Fresh ex vivo human skin tissue was cultured in an air–liquid interface and topically exposed to 20 chemicals, including true positive, misleading positive and true negative genotoxins. Based on the results obtained in the present study, the sensitivity, specificity and accuracy of the ex vivo skin comet assay to predict in vivo genotoxicity were 89%, 90% and 89%, respectively. Donor and experimental variability were mainly reflected in the magnitude of the response and not the difference between the presence and absence of a genotoxic response. The present study indicates that human skin obtained from surgery is a promising and robust model for safety evaluation of chemicals that are in direct contact with the skin. -- Highlights: ► We use human skin obtained from surgery for genotoxicity evaluation of chemicals. ► We use the comet assay as parameter for genotoxicity in ex vivo human skin. ► Sensitivity, specificity and accuracy to predict in vivo genotoxins are determined. ► Sensitivity, specificity and accuracy are 89%, 90% and 90%, respectively. ► The method

  20. The use of ex vivo human skin tissue for genotoxicity testing

    Energy Technology Data Exchange (ETDEWEB)

    Reus, Astrid A.; Usta, Mustafa [TNO Triskelion BV, Utrechtseweg 48, 3704 HE, Zeist (Netherlands); Krul, Cyrille A.M., E-mail: cyrille.krul@tno.nl [TNO, Utrechtseweg 48, 3704 HE Zeist (Netherlands)

    2012-06-01

    As a result of the chemical legislation concerning the registration, evaluation, authorization and restriction of chemicals (REACH), and the Seventh Amendment to the Cosmetics Directive, which prohibits animal testing in Europe for cosmetics, alternative methods for safety evaluation of chemicals are urgently needed. Current in vitro genotoxicity assays are not sufficiently predictive for the in vivo situation, resulting in an unacceptably high number of misleading positives. For many chemicals and ingredients of personal care products the skin is the first site of contact, but there are no in vitro genotoxicity assays available in the skin for additional evaluation of positive or equivocal responses observed in regulatory in vitro genotoxicity assays. In the present study ex vivo human skin tissue obtained from surgery was used for genotoxicity evaluation of chemicals by using the comet assay. Fresh ex vivo human skin tissue was cultured in an air–liquid interface and topically exposed to 20 chemicals, including true positive, misleading positive and true negative genotoxins. Based on the results obtained in the present study, the sensitivity, specificity and accuracy of the ex vivo skin comet assay to predict in vivo genotoxicity were 89%, 90% and 89%, respectively. Donor and experimental variability were mainly reflected in the magnitude of the response and not the difference between the presence and absence of a genotoxic response. The present study indicates that human skin obtained from surgery is a promising and robust model for safety evaluation of chemicals that are in direct contact with the skin. -- Highlights: ► We use human skin obtained from surgery for genotoxicity evaluation of chemicals. ► We use the comet assay as parameter for genotoxicity in ex vivo human skin. ► Sensitivity, specificity and accuracy to predict in vivo genotoxins are determined. ► Sensitivity, specificity and accuracy are 89%, 90% and 90%, respectively. ► The method

  1. In Vitro Genotoxic Effects of Four Helichrysum Species in Human Lymphocytes Cultures

    OpenAIRE

    Erolu, Erhan H; Hamzaolu, Ergin; Aksoy, Ahmet; Budak, Ümit; Özkul, Yusuf

    2010-01-01

    Helichrysum sanguineum, Helichrysum pamphylicum, Helichrysum orientale, Helichrysum noeanum (Asteraceae) are medicinal plants. For centuries, they have been used as tea in Turkey because of their medicinal properties. So far no scientifc evidence has been found in a literature survey regarding the genotoxic effects of these plants. This work evaluated the genotoxic effects on human lymphocyte cultures induced by methanol extracts of these plants, assayed in different concentrations (0.01, 0.0...

  2. Mutagenic and genotoxic activity of particulate matter MP2,5, in Pamplona, North Santander, Colombia

    OpenAIRE

    Martínez Montañez, Mónica Liseth; Meléndez Gélvez, Iván; Quijano Parra, Alfonso

    2012-01-01

    Objective: To study the mutagenic and genotoxic activities of particulate material (MP2,5 collected in Pamplona, Norte de Santander, Colombia.Materials and methods: MP2,5 was monitored by means of a Partisol 2025 sequential air sampler with Plus Palmflex quartz filters. The latter were subjected to two extraction procedures: Soxhlet extraction using dichloromethane-acetone; and ultrasonic extraction using dichloromethane, acetone and dichloromethane/ acetone mix. The mutagenic and genotoxic a...

  3. Critical elements for human health risk assessment of less than lifetime exposures.

    Science.gov (United States)

    Geraets, Liesbeth; Nijkamp, Monique M; Ter Burg, Wouter

    2016-11-01

    Less than lifetime exposure has confronted risk assessors as to how to interpret the risks for human health in case a chronic health-based limit is exceeded. Intermittent, fluctuating and peak exposures do not match with the basis of the chronic limit values possibly leading to conservative outcomes. This paper presents guidance on how to deal with human risk assessment of less than lifetime exposure. Important steps to be considered are characterization of the human exposure situation, evaluation whether the human less than lifetime exposure scenario corresponds to a non-chronic internal exposure: toxicokinetic and toxicodynamic considerations, and, finally, re-evaluation of the risk assessment. Critical elements for these steps are the mode of action, Haber's rule, and toxicokinetics (ADME) amongst others. Previous work for the endpoints non-genotoxic carcinogenicity and developmental toxicity is included in the guidance. The guidance provides a way to consider the critical elements, without setting default factors to correct for the less than lifetime exposure in risk assessment. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. The genotoxic contribution of wood smoke to indoor respirable suspended particles

    Energy Technology Data Exchange (ETDEWEB)

    Boone, P.M. (John B. Pierce Foundation Laboratory, New Haven, CT (USA)); Rossman, T.G. (New York Univ. Medical Center, New York (USA)); Daisey, J.M. (Lawrence Berkeley Laboratory, CA (USA))

    1989-01-01

    The effect of wood burning stoves on the genotoxicity of indoor respirable organic matter was investigated for four homes during the winter and spring of 1986. Paired samples, one collected when the stove was not used and one when wood was burned, were extracted with dichloromethane and acetone. Aliquots of the dichloromethane extracts were analyzed with and without metabolic activation using the Microscreen bioassay. The Microscreen is a rapid, sensitive bioassay which measures a broad genotoxic endpoint, {lambda}-prophage induction. Per nanogram of organic material, wood smoke proved to be a major source of indirect (observed with metabolic activation) but not direct genotoxins in homes. The increase in indirect genotoxicity for extracts from aerosol containing wood smoke is probably due to higher concentrations of polycyclic aromatic hydrocarbons in the wood smoke aerosol as well as other unidentified classes. The direct genotoxicity observed for extracts of aerosol not containing wood smoke decreased with metabolic activation. This direct genotoxicity may be related to cooking activities in the homes. The trends in genotoxicity observed per nanogram of organic material are more pronounced when expressed per m{sup 3} of air due to the higher percentage of extractable material in aerosol containing wood smoke.

  5. Cytotoxicity and genotoxicity of clothianidin in human lymphocytes with or without metabolic activation system.

    Science.gov (United States)

    Atlı Şekeroğlu, Zülal; Şekeroğlu, Vedat; Uçgun, Ebru; Kontaş Yedier, Seval; Aydın, Birsen

    2018-02-26

    Clothianidin (CHN) is a broad-spectrum neonicotinoid insecticide. Limited studies have been carried out on the cytotoxic and genotoxic effects of both CHN using different genotoxicity tests in human cells with or without human metabolic activation system (S9 mix). Therefore, the aim of this study is to investigate the cytotoxic and genotoxic effects of CHN and its metabolites on human lymphocyte cultures with or without S9 mix using chromosomal aberration (CA) and micronucleus (MN) tests. The cultures were treated with 25, 50, and 100 µg/ml of CHN in the presence (3 h treatment) and absence (48 h treatment) of S9 mix. Dimethyl sulfoxide (DMSO) was used as a solvent control. CHN showed cytotoxic and genotoxic effects due to significant decreases in mitotic index (MI) and nuclear division index (NDI), and significant increases in the CAs, aberrant cells, and MN formation in the absence of S9 mix when compared with solvent control. However, CHN did not significantly induce cytotoxicity and genotoxicity in the presence of S9 mix. Our results indicated that CHN has cytotoxic, cytostatic, and genotoxic potential on human peripheral blood lymphocyte cultures, but not its metabolites under the experimental conditions.

  6. Evaluation of genotoxicity of nitrile fragrance ingredients using in vitro and in vivo assays.

    Science.gov (United States)

    Bhatia, S P; Politano, V T; Api, A M

    2013-09-01

    Genotoxicity studies were conducted on a group of 8 fragrance ingredients that belong to the nitrile family. These nitriles are widely used in consumer products however there is very limited data in the literature regarding the genotoxicity of these nitriles. The 8 nitriles were assessed for genotoxicity using an Ames test, in vitro chromosome aberration test or in vitro micronucleus test. The positive results observed in the in vitro tests were further investigated using an in vivo micronucleus test. The results from these different tests were compared and these 8 nitriles are not considered to be genotoxic. Dodecanitrile and 2,2,3-trimethylcyclopent-3-enylacetonitrile were negative in the in vitro chromosome aberration test and in vitro micronucleus test, respectively. While citronellyl nitrile, 3-methyl-5-phenylpentanenitrile, cinnamyl nitrile, and 3-methyl-5-phenylpent-2-enenitrile revealed positive results in the in vitro tests, but confirmatory in vivo tests determined these nitriles to be negative in the in vivo micronucleus assay. The remaining two nitriles (benzonitrile and α-cyclohexylidene benzeneacetonitrile) were negative in the in vivo micronucleus test. This study aims to evaluate the genotoxicity potential of these nitriles as well as enrich the literature with genotoxicity data on fragrance ingredients. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Genotoxic and Antigenotoxic Assessment of Chios Mastic Oil by the In Vitro Micronucleus Test on Human Lymphocytes and the In Vivo Wing Somatic Test on Drosophila.

    Directory of Open Access Journals (Sweden)

    Dimitris Vlastos

    Full Text Available Chios mastic oil (CMO, the essential oil derived from Pistacia lentiscus (L. var. chia (Duham, has generated considerable interest because of its antimicrobial, anticancer, antioxidant and other beneficial properties. In the present study, the potential genotoxic activity of CMO as well as its antigenotoxic properties against the mutagenic agent mitomycin-C (MMC were evaluated by employing the in vitro Cytokinesis Block MicroNucleus (CBMN assay and the in vivo Somatic Mutation And Recombination Test (SMART. In the in vitro experiments, lymphocytes were treated with 0.01, 0.05 and 0.10% (v/v of CMO with or without 0.05 μg/ml MMC, while in the in vivo assay Drosophila larvae were fed with 0.05, 0.10, 0.50 and 1.00% (v/v of CMO with or without 2.50 μg/ml MMC. CMO did not significantly increase the frequency of micronuclei (MN or total wing spots, indicating lack of mutagenic or recombinogenic activity. However, the in vitro analysis suggested cytotoxic activity of CMO. The simultaneous administration of MMC with CMO did not alter considerably the frequencies of MMC-induced MN and wing spots showing that CMO doesn't exert antigenotoxic or antirecombinogenic action. Therefore, CMO could be considered as a safe product in terms of genotoxic potential. Even though it could not afford any protection against DNA damage, at least under our experimental conditions, its cytotoxic potential could be of interest.

  8. In vivo micronucleus test as a biomarker of genotoxicity in free-range goats from suspected contaminated environment

    Directory of Open Access Journals (Sweden)

    Afusat Jagun Jubril

    2017-09-01

    Conclusion: The finding indicates the prevalence and frequency of micronucleus as a biomarker of genotoxicity and an indicator of exposure to environmental genotoxic subtances. Hence, this highlights the relevance of these goats as important sentinel animal model. These findings, therefore, serve as a preliminary data for further studies on the latent genotoxic environmental contaminants and their potential deleterious impact. [J Adv Vet Anim Res 2017; 4(3.000: 281-287

  9. In vitro cytotoxicity and genotoxicity studies of gold nanoparticles-mediated photo-thermal therapy versus 5-fluorouracil

    International Nuclear Information System (INIS)

    Gomaa, Iman E.; Abdel Gaber, Sara A.; Bhatt, Samarth; Liehr, Thomas; Glei, Michael; El-Tayeb, Tarek A.; Abdel-Kader, Mahmoud H.

    2015-01-01

    This study evaluates tumour cell-killing efficacy of metallic gold nanoparticles (AuNPs)-mediated photo-thermal therapy (PTT) in comparison to 5-fluorouracil (5-FU) as a standard chemotherapeutic drug. It also focuses on the possible genetic abnormalities of both drugs in normal blood lymphocytes. Both 5-FU and light-activated spherical AuNPs of 15± nm diameter were used to target MCF-7 breast cancer cell line. Alkaline comet assay, standard karyotyping and multiplex fluorescent in situ hybridization were applied in order to investigate the respective possible genotoxic and mutagenic side effects that might result from the application of each therapeutic modality. Results showed that the LC25 of AuNPs-mediated PTT was achieved at a concentration of 100 µM for 12-h incubation and exposure to light energy of 50 J/cm 2 , while the same cytotoxic effect was obtained by incubating the MCF-7 cells with the same concentration of the chemotherapeutic drug 5-FU for 24 h. On the other hand, AuNPs showed insignificant genotoxic effect of DNA damage represented by 4.6 % in comparison to 18.58 % exerted by 5-FU. The chromosomal studies resulted in normal karyotypes for cells treated with AuNPs-mediated PTT, while those treated with 5-FU showed several types of numerical as well as structural chromosomal aberrations. In conclusion, compared to 5-FU, light-activated AuNPs-mediated PTT provides considerable efficacy in breast cancer cells killing with no genetic side effects under the proposed experimental conditions

  10. In vitro cytotoxicity and genotoxicity studies of gold nanoparticles-mediated photo-thermal therapy versus 5-fluorouracil

    Energy Technology Data Exchange (ETDEWEB)

    Gomaa, Iman E., E-mail: iman.gomaa@guc.edu.eg; Abdel Gaber, Sara A. [German University in Cairo (GUC), Faculty of Pharmacy and Biotechnology (Egypt); Bhatt, Samarth; Liehr, Thomas [Friedrich Schiller University, Jena University Hospital, Institute of Human Genetics (Germany); Glei, Michael [Friedrich Schiller University, Faculty of Biology and Pharmacy, Institute of Nutrition (Germany); El-Tayeb, Tarek A. [Cairo University, The National Institute for Laser Enhanced Sciences (NILES) (Egypt); Abdel-Kader, Mahmoud H. [German University in Cairo (GUC), Faculty of Pharmacy and Biotechnology (Egypt)

    2015-02-15

    This study evaluates tumour cell-killing efficacy of metallic gold nanoparticles (AuNPs)-mediated photo-thermal therapy (PTT) in comparison to 5-fluorouracil (5-FU) as a standard chemotherapeutic drug. It also focuses on the possible genetic abnormalities of both drugs in normal blood lymphocytes. Both 5-FU and light-activated spherical AuNPs of 15± nm diameter were used to target MCF-7 breast cancer cell line. Alkaline comet assay, standard karyotyping and multiplex fluorescent in situ hybridization were applied in order to investigate the respective possible genotoxic and mutagenic side effects that might result from the application of each therapeutic modality. Results showed that the LC25 of AuNPs-mediated PTT was achieved at a concentration of 100 µM for 12-h incubation and exposure to light energy of 50 J/cm{sup 2}, while the same cytotoxic effect was obtained by incubating the MCF-7 cells with the same concentration of the chemotherapeutic drug 5-FU for 24 h. On the other hand, AuNPs showed insignificant genotoxic effect of DNA damage represented by 4.6 % in comparison to 18.58 % exerted by 5-FU. The chromosomal studies resulted in normal karyotypes for cells treated with AuNPs-mediated PTT, while those treated with 5-FU showed several types of numerical as well as structural chromosomal aberrations. In conclusion, compared to 5-FU, light-activated AuNPs-mediated PTT provides considerable efficacy in breast cancer cells killing with no genetic side effects under the proposed experimental conditions.

  11. Cytotoxic, mutagenicity, and genotoxicity effects of guanylhydrazone derivatives.

    Science.gov (United States)

    Pinhatti, Valéria Rodrigues; da Silva, Juliana; Martins, Tales Leandro Costa; Moura, Dinara Jaqueline; Rosa, Renato Moreira; Villela, Izabel; Stopiglia, Cheila Denise Ottonelli; da Silva Santos, Selma; Scroferneker, Maria Lúcia; Machado, Carlos Renato; Saffi, Jenifer; Henriques, João Antonio Pêgas

    2016-08-01

    Several studies have reported that guanylhydrazones display a variety of desirable biological properties, such as antihypertensive, antibacterial, and antimalarial behaviour. They furthermore promote anti-pneumocystosis and anti-trypanosomiasis, exhibit antitumor activity, and show significant cytotoxicity against cancer cell lines. In this work, we have evaluated the cytotoxicity, mutagenicity, and genotoxicity of two guanylhydrazones derivatives, (E)-2-[(2,3-dimethoxyphenyl) methylene] hydrazine carboxymidamide hydrochloride (2,3-DMeB) and (E)-2-[(3,4-dimethoxyphenyl) methylene] hydrazine carboxymidamide hydrochloride (3,4-DMeB), in different biological models. Both 2,3-DMeB and 3,4-DMeB induce weak cytotoxic and mutagenic effects in bacteria and yeast. The genotoxicity of these compounds was determined in a fibroblast cell line (V79) using alkaline comet assay, as well as a modified comet assay with bacterial enzymes formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (EndoIII). Both guanylhydrazone derivatives induced DNA damage. Treatment of V79 cells with EndoIII and FPG proteins demonstrated a significant effect of 2,3-DMeB and 3,4-DMeB with respect to oxidized bases. In addition, the derivatives induced a significant increase in the frequency of micronucleated cells at high doses. The antifungal and anti-trypanosomal properties of these guanylhydrazone derivatives were also evaluated, and the obtained results suggest that 2,3-DMeB is more effective than 3,4-DMeB. The biological activity of 2,3-DMeB and 3,4-DMeB may thus be related, at least in part, to their oxidative potential, as well as to their ability to interact with DNA. Considering the previously reported in vitro antitumor activity of guanylhydrazone derivatives in combination with the lack of acute toxicity and the fact that DNA damage is only observed at high doses should render both compounds good candidates for in vivo studies on antitumor activity. Copyright © 2016 Elsevier B

  12. Genotoxic, epigenetic, and transcriptomic effects of tamoxifen in mouse liver

    International Nuclear Information System (INIS)

    Conti, Aline de; Tryndyak, Volodymyr; Churchwell, Mona I.; Melnyk, Stepan; Latendresse, John R.; Muskhelishvili, Levan; Beland, Frederick A.; Pogribny, Igor P.

    2014-01-01

    Highlights: • Treatment of female mice with tamoxifen caused genotoxic changes in the livers. • Tamoxifen treatment did not affect the hepatic epigenome. • Tamoxifen caused over-expression of hepatic Lcn13 and Pparγ genes. • Mice are resistant to tamoxifen-induced liver carcinogenesis and fatty liver injury. - Abstract: Tamoxifen is a non-steroidal anti-estrogenic drug widely used for the treatment and prevention of breast cancer in women; however, there is evidence that tamoxifen is hepatocarcinogenic in rats, but not in mice. Additionally, it has been reported that tamoxifen may cause non-alcoholic fatty liver disease (NAFLD) in humans and experimental animals. The goals of the present study were to (i) investigate the mechanisms of the resistance of mice to tamoxifen-induced hepatocarcinogenesis, and (ii) clarify effects of tamoxifen on NAFLD-associated liver injury. Feeding female WSB/EiJ mice a 420 p.p.m. tamoxifen-containing diet for 12 weeks resulted in an accumulation of tamoxifen-DNA adducts, (E)-α-(deoxyguanosin-N 2 -yl)-tamoxifen (dG-TAM) and (E)-α-(deoxyguanosin-N 2 -yl)-N-desmethyltamoxifen (dG-DesMeTAM), in the livers. The levels of hepatic dG-TAM and dG-DesMeTAM DNA adducts in tamoxifen-treated mice were 578 and 340 adducts/108 nucleotides, respectively, while the extent of global DNA and repetitive elements methylation and histone modifications did not differ from the values in control mice. Additionally, there was no biochemical or histopathological evidence of NAFLD-associated liver injury in mice treated with tamoxifen. A transcriptomic analysis of differentially expressed genes demonstrated that tamoxifen caused predominantly down-regulation of hepatic lipid metabolism genes accompanied by a distinct over-expression of the lipocalin 13 (Lcn13) and peroxisome proliferator receptor gamma (Pparγ), which may prevent the development of NAFLD. The results of the present study demonstrate that the resistance of mice to tamoxifen

  13. Genotoxicity assessment of ethylenediamine dinitrate (EDDN) and diethylenetriamine trinitrate (DETN).

    Science.gov (United States)

    Reddy, Gunda; Song, Jian; Kirby, Paul; Johnson, Mark S

    2011-12-24

    Ethylenediamine dinitrate (EDDN) and diethylenetriamine trinitrate (DETN) are relatively insensitive explosive compounds that are being explored as safe alternatives to other more sensitive compounds. When used in combination with other high explosives they are an improvement and may provide additional safety during storage and use. The genetic toxicity of these compounds was evaluated to predict the potential adverse human health effects from exposure by using a standard genetic toxicity test battery which included: a gene mutation test in bacteria (Ames), an in vitro Chinese Hamster Ovary (CHO) cell chromosome aberration test and an in vivo mouse micronucleus test. The results of the Ames test showed that EDDN increased the mean number of revertants per plate with strain TA100, without activation, at 5000μg/plate compared to the solvent control, which indicated a positive result. No positive results were observed with the other tester strains with or without activation in Salmonella typhimurium strains TA98, TA1535, TA1537, and Escherichia coli strain WP2 uvrA. DETN was negative for all Salmonella tester strains and E. coli up to 5000μg/plate both with and without metabolic activation. The CHO cell chromosome aberration assay was performed using EDDN and DETN at concentrations up to 5000μg/mL. The results indicate that these compounds did not induce structural chromosomal aberrations at all tested concentrations in CHO cells, with or without metabolic activation. EDDN and DETN, when tested in vivo in the CD-1 mouse at doses up to 2000mg/kg, did not induce any significant increase in the number of micronuclei in bone marrow erythrocytes. These studies demonstrate that EDDN is mutagenic in one strain of Salmonella (TA100) but was negative in other strains, for in vitro induction of chromosomal aberrations in CHO cells, and for micronuclei in the in vivo mouse micronucleus assay. DETN was not genotoxic in all in vitro and in vivo tests. These results show the in

  14. Therapeutic Response to Non-genotoxic Activation of p53 by Nutlin3a Is Driven by PUMA-Mediated Apoptosis in Lymphoma Cells

    Directory of Open Access Journals (Sweden)

    Liz J. Valente

    2016-03-01

    Full Text Available Nutlin3a is a small-molecule antagonist of MDM2 that promotes non-genotoxic activation of p53 through p53 protein stabilization and transactivation of p53 target genes. Nutlin3a is the forerunner of a class of cancer therapeutics that have reached clinical trials. Using transgenic and gene-targeted mouse models lacking the critical p53 target genes, p21, Puma, and Noxa, we found that only loss of PUMA conferred profound protection against Nutlin3a-induced killing in both non-transformed lymphoid cells and Eμ-Myc lymphomas in vitro and in vivo. CRISPR/Cas9-mediated targeting of the PUMA gene rendered human hematopoietic cancer cell lines markedly resistant to Nutlin3a-induced cell death. These results demonstrate that PUMA-mediated apoptosis, but not p21-mediated cell-cycle arrest or senescence, is a critical determinant of the therapeutic response to non-genotoxic p53 activation by Nutlin3a. Importantly, in human cancer, PUMA expression may predict patient responses to treatment with MDM2 antagonists.

  15. Genotoxicity of antiobesity drug orlistat and effect of caffeine intervention: an in vitro study.

    Science.gov (United States)

    Chakrabarti, Manoswini; Ghosh, Ilika; Jana, Aditi; Ghosh, Manosij; Mukherjee, Anita

    2017-07-01

    Obesity is a major global health problem associated with various adverse effects. Pharmacological interventions are often necessary for the management of obesity. Orlistat is an FDA-approved antiobesity drug which is a potent inhibitor of intestinal lipases. In the current study, orlistat was evaluated for its genotoxic potential in human lymphocyte cells in vitro and was compared with that of another antiobesity drug sibutramine, presently withdrawn from market due its undesirable health effects. Caffeine intake may be an additional burden in people using anorectic drugs, therefore, further work is needed to be carried out to evaluate the possible effects of caffeine on orlistat-induced DNA damage. Human lymphocytes were exposed to orlistat (250, 500 and 1000 μg/ml), sibutramine (250, 500 and 1000 μg/ml) and caffeine (25, 50, 75, 100, 125 and 150 μg/ml) to assess their genotoxicity by comet assay in vitro. In addition, lymphocytes were co-incubated with caffeine (50, 75 and 100 μg/ml) and a single concentration of orlistat (250 μg/ml). Orlistat and sibutramine were genotoxic at all concentrations tested, sibutramine being more genotoxic. Caffeine was found to be genotoxic at concentrations 125 μg/ml and above. Co-treatment of orlistat with non-genotoxic concentrations (50, 75 and 100 μg/ml) of caffeine lead to a decrease in DNA damage. Orlistat can induce DNA damage in human lymphocytes in vitro and caffeine was found to reduce orlistat-induced genotoxicity.

  16. The cytotoxicity and genotoxicity of soluble and particulate cobalt in human lung fibroblast cells

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Leah J.; Holmes, Amie L. [Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Maine Center for Environmental Toxicology and Health, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Department of Applied Medical Science, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Kandpal, Sanjeev Kumar; Mason, Michael D. [Department of Chemical and Biological Engineering, University of Maine, Orono, ME (United States); Zheng, Tongzhang [Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT (United States); Wise, John Pierce, E-mail: John.Wise@usm.maine.edu [Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Maine Center for Environmental Toxicology and Health, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Department of Applied Medical Science, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States)

    2014-08-01

    Cobalt exposure is increasing as cobalt demand rises worldwide due to its use in enhancing rechargeable battery efficiency, super-alloys, and magnetic products. Cobalt is considered a possible human carcinogen with the lung being a primary target. However, few studies have considered cobalt-induced toxicity in human lung cells. Therefore, in this study, we sought to determine the cytotoxicity and genotoxicity of particulate and soluble cobalt in human lung cells. Cobalt oxide and cobalt chloride were used as representative particulate and soluble cobalt compounds, respectively. Exposure to both particulate and soluble cobalt induced a concentration-dependent increase in cytotoxicity, genotoxicity, and intracellular cobalt ion levels. Based on intracellular cobalt ion levels, we found that soluble cobalt was more cytotoxic than particulate cobalt while particulate and soluble cobalt induced similar levels of genotoxicity. However, soluble cobalt induced cell cycle arrest indicated by the lack of metaphases at much lower intracellular cobalt concentrations compared to cobalt oxide. Accordingly, we investigated the role of particle internalization in cobalt oxide-induced toxicity and found that particle-cell contact was necessary to induce cytotoxicity and genotoxicity after cobalt exposure. These data indicate that cobalt compounds are cytotoxic and genotoxic to human lung fibroblasts, and solubility plays a key role in cobalt-induced lung toxicity. - Highlights: • Particulate and soluble cobalt are cytotoxic and genotoxic to human lung cells. • Soluble cobalt induces more cytotoxicity compared to particulate cobalt. • Soluble and particulate cobalt induce similar levels of genotoxicity. • Particle-cell contact is required for particulate cobalt-induced toxicity.

  17. A whole-cell bioreporter assay for quantitative genotoxicity evaluation of environmental samples.

    Science.gov (United States)

    Jiang, Bo; Li, Guanghe; Xing, Yi; Zhang, Dayi; Jia, Jianli; Cui, Zhisong; Luan, Xiao; Tang, Hui

    2017-10-01

    Whole-cell bioreporters have emerged as promising tools for genotoxicity evaluation, due to their rapidity, cost-effectiveness, sensitivity and selectivity. In this study, a method for detecting genotoxicity in environmental samples was developed using the bioluminescent whole-cell bioreporter Escherichia coli recA::luxCDABE. To further test its performance in a real world scenario, the E. coli bioreporter was applied in two cases: i) soil samples collected from chromium(VI) contaminated sites; ii) crude oil contaminated seawater collected after the Jiaozhou Bay oil spill which occurred in 2013. The chromium(VI) contaminated soils were pretreated by water extraction, and directly exposed to the bioreporter in two phases: aqueous soil extraction (water phase) and soil supernatant (solid phase). The results indicated that both extractable and soil particle fixed chromium(VI) were bioavailable to the bioreporter, and the solid-phase contact bioreporter assay provided a more precise evaluation of soil genotoxicity. For crude oil contaminated seawater, the response of the bioreporter clearly illustrated the spatial and time change in genotoxicity surrounding the spill site, suggesting that the crude oil degradation process decreased the genotoxic risk to ecosystem. In addition, the performance of the bioreporter was simulated by a modified cross-regulation gene expression model, which quantitatively described the DNA damage response of the E. coli bioreporter. Accordingly, the bioluminescent response of the bioreporter was calculated as the mitomycin C equivalent, enabling quantitative comparison of genotoxicities between different environmental samples. This bioreporter assay provides a rapid and sensitive screening tool for direct genotoxicity assessment of environmental samples. Copyright © 2017. Published by Elsevier Ltd.

  18. Bacterial reduction in genotoxicity of Direct Red 28 dye.

    Science.gov (United States)

    Bafana, Amit; Jain, Minakshi; Agrawal, Gaurav; Chakrabarti, Tapan

    2009-03-01

    Direct Red 28 (DR28) is a benzidine-based azo dye widely used in several countries. It has also been a subject of intense research for its anti-prion activity. Like other benzidine-based azo dyes, it is also carcinogenic and toxic. However, there are very few studies addressing its detoxification. In the present study, a Bacillus velezensis strain was used for detoxification of DR28. Toxicity was checked by a battery of highly sensitive genotoxicity assays like comet assay, DNA ladder formation, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and flow cytometric Annexin V binding assay. HL-60 cell line was used as the test system. All the assays showed an initial increase in toxicity upon biodegradation due to release of mutagenic products, like benzidine and 4-aminobiphenyl, from the dye. These intermediates caused significant DNA damage and induced apoptosis in HL-60 cells. Then the culture degraded these mutagenic intermediates, due to which the toxicity was reduced gradually, finally resulting in nearly complete detoxification.

  19. Assessment of mutagenic, antimutagenic and genotoxicity effects of Mimosa tenuiflora

    Directory of Open Access Journals (Sweden)

    Viviane A. Silva

    2013-02-01

    Full Text Available Genotoxic effects of Mimosa tenuiflora (Willd. Poir, Fabaceae, were investigated by using both micronucleus test and bacterial reverse mutation assay in Salmonella typhimurium TA97, TA98, TA100, TA102 respectively. In respect of Ames test results show that the extract does not induce mutations in any strains of Salmonella typhimurium tested since the mutagenicity index is less than 2. In the antimutagenic effect was observed that the extract at the concentrations tested significantly decreased the mutagenicity index of all strains tested which characterized the extract as antimutagenic in these conditions. In the micronucleus test in vivo, we observed that the concentrations used did not induce an increase in the frequency of micronucleus in normochromatic erythrocytes of mice. Therefore, we concluded that the extract of M. tenuiflora is not mutagenic in the absence of exogenous metabolizing system and does not induce an increase in the frequency of the micronucleus characterized as an agent not mutagenic in these conditions. Further studies of toxicity need to be made to the use of this plant in the treatment of diseases to be stimulated.

  20. Assessment of mutagenic, antimutagenic and genotoxicity effects of Mimosa tenuiflora

    Directory of Open Access Journals (Sweden)

    Viviane A. Silva

    2013-04-01

    Full Text Available Genotoxic effects of Mimosa tenuiflora (Willd. Poir, Fabaceae, were investigated by using both micronucleus test and bacterial reverse mutation assay in Salmonella typhimurium TA97, TA98, TA100, TA102 respectively. In respect of Ames test results show that the extract does not induce mutations in any strains of Salmonella typhimurium tested since the mutagenicity index is less than 2. In the antimutagenic effect was observed that the extract at the concentrations tested significantly decreased the mutagenicity index of all strains tested which characterized the extract as antimutagenic in these conditions. In the micronucleus test in vivo, we observed that the concentrations used did not induce an increase in the frequency of micronucleus in normochromatic erythrocytes of mice. Therefore, we concluded that the extract of M. tenuiflora is not mutagenic in the absence of exogenous metabolizing system and does not induce an increase in the frequency of the micronucleus characterized as an agent not mutagenic in these conditions. Further studies of toxicity need to be made to the use of this plant in the treatment of diseases to be stimulated.

  1. Nano-QSAR: Genotoxicity of Multi-Walled Carbon Nanotubes

    International Nuclear Information System (INIS)

    Toropova, A. P.; Toropov, A. A.; Rallo, R.; Leszczynska, D.; Leszczynski, J.

    2016-01-01

    The study was carried out to develop an efficient approach for prediction the genotoxicity of carbon nano tubes. The experimental data on the bacterial reverse mutation test (TA100) on multi-walled carbon nano tubes was collected from the literature and examined as an endpoint. By means of the optimal descriptors calculated with the Monte Carlo method a mathematical model of the endpoint was built up. The model is represented by a function of: (i) dose (μg/plate); (ii) metabolic activation (i.e. with S9 mix or without S9 mix); and (iii) two types of multi-walled carbon nano tubes. The above listed conditions were represented by so-called quasi-SMILES. Simplified molecular input-line entry system (SMILES) is a tool for representation of molecular structure. The quasi-SMILES is a tool to represent physicochemical and / or biochemical conditions for building up a predictive model. Thus, instead of well-known paradigm of predictive modeling “endpoint is a mathematical function of molecular structure” a fresh paradigm “endpoint is a mathematical function of available eclectic data (conditions) is suggested.

  2. Sewage sludge does not induce genotoxicity and carcinogenesis

    Science.gov (United States)

    Silva, Paula Regina Pereira; Barbisan, Luis Fernando; Dagli, Maria Lúcia Zaidan; Saldiva, Paulo Hilário Nascimento

    2012-01-01

    Through a series of experiments, the genotoxic/mutagenic and carcinogenic potential of sewage sludge was assessed. Male Wistar rats were randomly assigned to four groups: Group 1 - negative control; Group 2 - liver carcinogenesis initiated by diethylnitrosamine (DEN; 200 mg/kg i.p.); Group 3 and G4-liver carcinogenesis initiated by DEN and fed 10,000 ppm or 50,000 ppm of sewage sludge. The animals were submitted to a 70% partial hepatectomy at the 3rd week. Livers were processed for routine histological analysis and immunohistochemistry, in order to detect glutathione S-transferase positive altered hepatocyte foci (GST-P+ AHF). Peripheral blood samples for the comet assay were obtained from the periorbital plexus immediately prior to sacrificing. Polychromatic erythrocytes (PCEs) were analyzed in femoral bone-marrow smears, and the frequencies of those micronucleated (MNPCEs) registered. There was no sewage-sludge-induced increase in frequency of either DNA damage in peripheral blood leucocytes, or MNPCEs in the femoral bone marrow. Also, there was no increase in the levels of DNA damage, in the frequency of MNPCEs, and in the development of GST-P AHF when compared with the respective control group. PMID:23055806

  3. Metabolism and genotoxicity of aromatic amines in aquatic organisms

    International Nuclear Information System (INIS)

    Knezovich, J.P.; Krauter, P.W.; Lawton, M.P.; Harrison, F.L.

    1987-01-01

    Marine mussels (Mytilus edulis) and bullfrog tadpoles (Rana catesbeiana) were used to investigate the comparative metabolism and genotoxicity of aromatic amines in vivo. These organisms were selected because they possess distinctly different metabolic capabilities: mussels lack an active mixed-function-oxidase enzyme system that is present in most other organisms, including amphibians. Using 14 C-labeled chemical probes (o- and p-toluidine, 2-aminofluorene (2-AF), and 2-acetylaminofluorene (2-AAF)), mussels and tadpoles well dosed with individual compounds by direct immersion in aqueous solutions. The identities of metabolites were then determined by HPLC and GC/MS methods. Results indicate that the N-conjugating pathways used by mussels result primarily in the detoxification of aromatic amines by limiting the amount of primary amine available for activation. The tadpoles excreted a number of 2-AAF metabolites but did form DNA and protein adducts in the liver. Induction of micronuclei in the peripheral red blood cells was also demonstrated. The tadpole was shown to be a sensitive biological indicator of pollution in aquatic ecosystems

  4. Cytotoxic and genotoxic effects of silver nanoparticles in testicular cells

    International Nuclear Information System (INIS)

    Asare, Nana; Instanes, Christine; Sandberg, Wiggo J.; Refsnes, Magne; Schwarze, Per; Kruszewski, Marcin; Brunborg, Gunnar

    2012-01-01

    Serious concerns have been expressed about potential risks of engineered nanoparticles. Regulatory health risk assessment of such particles has become mandatory for the safe use of nanomaterials in consumer products and medicines; including the potential effects on reproduction and fertility, are relevant for this risk evaluation. In this study, we examined effects of silver particles of nano- (20 nm) and submicron- (200 nm) size, and titanium dioxide nanoparticles (TiO 2 -NPs; 21 nm), with emphasis on reproductive cellular- and genotoxicity. Ntera2 (NT2, human testicular embryonic carcinoma cell line), and primary testicular cells from C57BL6 mice of wild type (WT) and 8-oxoguanine DNA glycosylase knock-out (KO, mOgg1 −/− ) genotype were exposed to the particles. The latter mimics the repair status of human testicular cells vs oxidative damage and is thus a suitable model for human male reproductive toxicity studies. The results suggest that silver nano- and submicron-particles (AgNPs) are more cytotoxic and cytostatic compared to TiO 2 -NPs, causing apoptosis, necrosis and decreased proliferation in a concentration- and time-dependent manner. The 200 nm AgNPs in particular appeared to cause a concentration-dependent increase in DNA-strand breaks in NT2 cells, whereas the latter response did not seem to occur with respect to oxidative purine base damage analysed with any of the particles tested.

  5. Recent perspectives on the relations between faecal mutagenicity, genotoxicity and diet

    Directory of Open Access Journals (Sweden)

    Silvia eGratz

    2011-03-01

    Full Text Available DNA damage is an essential component of the genesis of colonic cancer. Gut microbial products and food components are thought to be principally responsible for the damage that initiates disease progression. Modified Ames tests and Comet assays have been developed for measuring mutagenicity and genotoxicity. Their relevance to oncogenesis remains to be confirmed, as does the relative importance of different mutagenic and genotoxic compounds present in faecal water and the bacteria involved in their metabolism. Dietary intervention studies provide clues to the likely risks of oncogenesis. High-protein diets lead to increases in N-nitroso compounds in faecal water and greater DNA damage as measured by the Comet assay, for example. Other dietary interventions, such as non-digestible carbohydrates and probiotics, may lead to lower faecal genotoxicity. In order to make recommendations to the general public, we must develop a better understanding of how genotoxic compounds are formed in the colon, how accurate the Ames and Comet assays are, and how diet affects genotoxicity.

  6. Mutagenic and genotoxic activity of particulate matter MP2,5, in Pamplona, North Santander, Colombia

    Directory of Open Access Journals (Sweden)

    Martínez Montañez, Mónica Liseth

    2012-10-01

    Full Text Available Objective: To study the mutagenic and genotoxic activities of particulate material (MP2,5 collected in Pamplona, Norte de Santander, Colombia.Materials and methods: MP2,5 was monitored by means of a Partisol 2025 sequential air sampler with Plus Palmflex quartz filters. The latter were subjected to two extraction procedures: Soxhlet extraction using dichloromethane-acetone; and ultrasonic extraction using dichloromethane, acetone and dichloromethane/ acetone mix. The mutagenic and genotoxic activities were determined for each extract.Results: This is the first study conducted in Colombia that reports the mutagenic and genotoxic activities associated with particulate matter (MP2,5 taken from vehicular emissions in Pamplona, Norte de Santander. The mutagenic assay determined by the Ames test using Salmonella typhimurium strains TA98 and TA100 showed a high direct mutagenic activity in the analyzed extracts. On the other hand, the genotoxic activity, determined by means of the comet assay, was high too.Conclusion: Particulate material (MP2,5 present in air samples in Pamplona (northeastern Colombia is a risk factor for the exposed population because it can directly induce mutations and also cause genotoxic damage.

  7. AFFINITY BIOSENSOR BASED ON SCREEN-PRINTED ELECTRODE MODIFIED WITH DNA FOR GENOTOXIC COMPOUNDS DETECTION

    Directory of Open Access Journals (Sweden)

    Bambang Kuswandi

    2010-06-01

    Full Text Available An electrochemical method for the detection of the genotoxic compounds using a DNA-modified electrode was developed. This electrode was successfully used for the electrochemical detection of genotoxic compounds in water samples. The electrochemical results clearly demonstrated that, the development is related to the molecular interaction between the surface-linked DNA obtained from calf thymus and the target compounds, such as pollutants, in order to develop a simple device for rapid screening of genotoxic compounds in environmental samples. The detection of such compounds was measured by their effect on the oxidation signal of the guanine peak of the DNA immobilised on the surface of carbon based Screen-Printed Electrode (SPE in disposable mode, and monitored by square-wave voltametric analysis. The DNA biosensor is able to detect known intercalating and groove-binding genotoxic compounds such as Dioxin, Bisphenol A, PCBs, and Phtalates. Application to real water samples is discussed and reported.   Keywords: electrochemical, screen-printed electrode, DNA biosensor, genotoxic compounds

  8. Non-genotoxic carcinogens: early effects on gap junctions, cell proliferation and apoptosis in the rat

    International Nuclear Information System (INIS)

    Mally, Angela; Chipman, James Kevin

    2002-01-01

    Non-genotoxic carcinogens are thought to induce tumour formation by disturbing the balance between cell growth and cell death. Gap junctions (GJ) contribute to the maintenance of tissue homeostasis by allowing the intercellular exchange of growth regulatory signals and potential inhibition of GJ intercellular communication through loss of connexin (Cx) plaques has been shown to be involved in the cancer process. We have investigated the time- and dose-dependent effects of the non-genotoxic hepatocarcinogens Wy-14,643, 2,3,7,8-tetrachlorodibenzo-p-dioxin, methapyrilene and hexachlorobenzene and the male rat kidney carcinogens chloroform, p-dichlorobenzene and d-limonene on gap junction plaque expression in relation to proliferation and apoptosis. With the exception of limonene, all non-genotoxic carcinogens significantly reduced the expression of GJ plaques containing Cx32 in their respective target tissue. No dose-dependent, significant effects were seen in non-target organs. Although alteration of Cx32 expression did not appear to correlate with induction of cell proliferation, out data suggest that the interaction of both processes--interference of GJ coupled with a proliferative stimulus (at the carcinogenic dose)--may be important in non-genotoxic carcinogenesis and provide a potential alert for non-genotoxic carcinogens in short-term toxicity tests

  9. Assessment of Genotoxicity of Ionizing radiation using Tradescantia-Comet assay

    Energy Technology Data Exchange (ETDEWEB)

    Han, Min; Ryu, Tae Ho; Hyun, Kyung Man; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Wilhelmova, Nad [Institute of Experimental Botany, Prague (Czech Republic)

    2010-05-15

    Over the last two decades, several new methodologies for the detection of DNA damage have been developed. The comet assay is currently used in different areas of biological sciences to detect DNA damage. The comet assay, also called the single cell gel electrophoresis (SCGE) was first introduced by Ostling and Johanson as a microelectrophoretic technique for the direct visualization of DNA damage in individual cells. The comet assay, due to its simplicity, sensitivity and need of a few cells, is ideal as a short-term genotoxicity test. The comet assay can theoretically be applied to every type of eukaryotic cell, including plant cells. Plants are very useful as monitors of genetic effects caused by pollution in the atmosphere, water and soil. Although the genotoxic effects detected by Tradescantia tests cannot be associated with mutagenesis or even carcinogenesis in humans, these bioassays are very useful tools for screening the mutagenic potential in the environment. Experiments were conducted to study the genotoxic effects of ionizing radiations on the genome integrity, particularly of Tradescantia. The increasingly frequent use of Tradescantia as a sensitive environmental bioindicator of genotoxic effects. This study was designed to assess the genotoxicity of ionizing radiation using Tradescnatia-comet assay

  10. Minimum critical mass systems

    International Nuclear Information System (INIS)

    Dam, H. van; Leege, P.F.A. de

    1987-01-01

    An analysis is presented of thermal systems with minimum critical mass, based on the use of materials with optimum neutron moderating and reflecting properties. The optimum fissile material distributions in the systems are obtained by calculations with standard computer codes, extended with a routine for flat fuel importance search. It is shown that in the minimum critical mass configuration a considerable part of the fuel is positioned in the reflector region. For 239 Pu a minimum critical mass of 87 g is found, which is the lowest value reported hitherto. (author)

  11. Criticality accident in Argentina

    International Nuclear Information System (INIS)

    Oliveira, A.R. de.

    1984-01-01

    A recent criticality type accident, ocurred in Argetina, is commented. Considerations about the nature of the facility where this accident took place, its genesis, type of operation carried out on the day of the event, and the medical aspects involved are done. (Author) [pt

  12. Evaluation of acute toxicity, genotoxicity and inhibitory effect on acute inflammation of an ethanol extract of Morus alba L. (Moraceae) in mice.

    Science.gov (United States)

    Oliveira, Alisson Macário de; Nascimento, Matheus Ferreira do; Ferreira, Magda Rhayanny Assunção; Moura, Danielle Feijó de; Souza, Talita Giselly Dos Santos; Silva, Gabriela Cavalcante da; Ramos, Eduardo Henrique da Silva; Paiva, Patrícia Maria Guedes; Medeiros, Paloma Lys de; Silva, Teresinha Gonçalves da; Soares, Luiz Alberto Lira; Chagas, Cristiano Aparecido; Souza, Ivone Antônia de; Napoleão, Thiago Henrique

    2016-12-24

    not result in genotoxicity and considerably reduced (58.6-65.6% inhibition) leukocyte migration in all doses evaluated, in comparison with the negative control. The ethanol extract from M. alba leaves administered intraperitoneally possesses a greater degree of toxicity in mice when compared to per os administration. The extract was not genotoxic when ingested by mice and exhibited a highly inhibitory effect against acute inflammation, which is probably linked to the presence of chlorogenic acid and flavonoids in the composition. This work contributes to the determination of safety of the medicinal use of M. alba leaves. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Genotoxicity of drinking water treated with different disinfectants and effects of disinfection conditions detected by umu-test.

    Science.gov (United States)

    Nie, Xuebiao; Liu, Wenjun; Zhang, Liping; Liu, Qing

    2017-06-01

    The genotoxicity of drinking water treated with 6 disinfection methods and the effects of disinfection conditions were investigated using the umu-test. The pretreatment procedure of samples for the umu-test was optimized for drinking water analysis. The results of the umu-test were in good correlation with those of the Ames-test. The genotoxicity and production of haloacetic acids (HAAs) were the highest for chlorinated samples. UV+chloramination is the safest disinfection method from the aspects of genotoxicity, HAA production and inactivation effects. For chloramination, the effects of the mass ratio of Cl 2 to N of chloramine on genotoxicity were also studied. The changes of genotoxicity were different from those of HAA production, which implied that HAA production cannot represent the genotoxic potential of water. The genotoxicity per chlorine decay of chlorination and chloramination had similar trends, indicating that the reaction of organic matters and chlorine made a great contribution to the genotoxicity. The results of this study are of engineering significance for optimizing the operation of waterworks. Copyright © 2016. Published by Elsevier B.V.

  14. Genotoxicity of clays with potential use in biopolymers for food packaging

    DEFF Research Database (Denmark)

    Sharma, Anoop Kumar; Mortensen, Alicja; Hadrup, Niels

    Genotoxicity of clays with potential use in biopolymers for food packaging Plastics produced from biopolymers are of commercial interest as they are manufactured from renewable resources such as agricultural crop wastes and have the potential to meet environmental and health requirements. Biopoly......Genotoxicity of clays with potential use in biopolymers for food packaging Plastics produced from biopolymers are of commercial interest as they are manufactured from renewable resources such as agricultural crop wastes and have the potential to meet environmental and health requirements...... in crude suspensions (suspended in cell culture medium) and crude suspensions filtrated through a 0.2 µm pore size filter in order to investigate the potential effect of “nanoparticles” only. The two clays showed noticeable differences in genotoxicity; both crude and filtered suspensions of Cloisite...

  15. Moesin Is a Biomarker for the Assessment of Genotoxic Carcinogens in Mouse Lymphoma

    Science.gov (United States)

    Lee, Yoen Jung; Choi, In-Kwon; Sheen, Yhun Yhong; Park, Sue Nie; Kwon, Ho Jeong

    2012-01-01

    1,2-Dibromoethane and glycidol are well known genotoxic carcinogens, which have been widely used in industry. To identify a specific biomarker for these carcinogens in cells, the cellular proteome of L5178Y mouse lymphoma cells treated with these compounds was analyzed by 2-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry (MS). Of 50 protein spots showing a greater than 1.5-fold increase or decrease in intensity compared to control cells on a 2-D gel, we focused on the candidate biomarker moesin. Western analysis using monoclonal rabbit anti-moesin confirmed the identity of the protein and its increased level of expression upon exposure to the carcinogenic compounds. Moesin expression also increased in cells treated with six additional genotoxic carcinogens, verifying that moesin could serve as a biomarker to monitor phenotypic change upon exposure to genotoxic carcinogens in L5178Y mouse lymphoma cells. PMID:22358511

  16. Effect of Boron Toxicity on Oxidative Stress and Genotoxicity in Wheat (Triticum aestivum L.).

    Science.gov (United States)

    Çatav, Şükrü Serter; Genç, Tuncer Okan; Kesik Oktay, Müjgan; Küçükakyüz, Köksal

    2018-04-01

    Boron (B) toxicity, which occurs in semi-arid and arid environments, can adversely affect the growth and yield of many plants. The aim of this study was to determine the effects of different concentrations of boric acid (3, 6, 9 and 12 mM) on growth, oxidative stress and genotoxicity parameters in root and shoot tissues of wheat seedlings. Our results indicate that B stress inhibits root and shoot growth of wheat in a concentration-dependent manner, and leads to increases in TBARS and H 2 O 2 contents in shoot tissue. Moreover, our findings suggest that high concentrations of B may exert a genotoxic effect on wheat. To the best of our knowledge, this is the first report to evaluate the effect of B stress on genotoxicity in both root and shoot tissues of wheat.

  17. Benzene-induced genotoxicity in mice in vivo detected by the alkaline comet assay

    DEFF Research Database (Denmark)

    Tuo, J; Loft, S; Thomsen, M S

    1996-01-01

    was further increased to 5.4-fold and 6.6-fold of the control values, respectively (p propylene glycol (5 microliters/g b.wt., twice with a 60-min interval), a selective CYP2E1 inhibitor, reduced the increase in the tail length by about half at all doses in both cell types (p ...The myelotoxic and genotoxic effects of benzene have been related to oxidative DNA damage after metabolism by CYP2E1. Single cell gel electrophoresis (alkaline comet assay) detects DNA damage and may thus be a convenient method for the study of benzene genotoxicity. Benzene exposure to NMRI mice.......01). By comparing our data with those from genotoxicity studies on benzene using other methods, we conclude that the 'alkaline comet assay' is a sensitive method to detect DNA damage induced by benzene. We also infer that CYP2E1 contributes, at least partly, to the formation of the 'comet'-inducing metabolites...

  18. In Vitro Genotoxic Effects of Four Helichrysum Species in Human Lymphocytes Cultures

    Directory of Open Access Journals (Sweden)

    Erhan H Erolu

    2010-01-01

    Full Text Available Helichrysum sanguineum, Helichrysum pamphylicum, Helichrysum orientale, Helichrysum noeanum (Asteraceae are medicinal plants. For centuries, they have been used as tea in Turkey because of their medicinal properties. So far no scientifc evidence has been found in a literature survey regarding the genotoxic effects of these plants. This work evaluated the genotoxic effects on human lymphocyte cultures induced by methanol extracts of these plants, assayed in different concentrations (0.01, 0.05, 0.1, 0.5 and 1 mg/mL. According to the results, Helichrysum noeanum, Helichrysum pamphylicum and Helichrysum sanguineum induced the formation of micronuclei and decreased the mitotic and replication indexes. Helichrysum orientale did not affect these parameters, whereas Helichrysum noeanum, Helichrysum pamphylicum and Helichrysum sanguineum were clearly genotoxic. They should therefore not be used freely in alternative medicine, although their antiproliferative activity may suggest antimitotic and anticarcinogenic properties. Helichrysum orientale could be used in alternative medicine.

  19. In vitro genotoxic effects of four Helichrysum species in human lymphocytes cultures.

    Science.gov (United States)

    Erolu, Erhan H; Hamzaolu, Ergin; Aksoy, Ahmet; Budak, Ümit; Özkul, Yusuf

    2010-01-01

    Helichrysum sanguineum, Helichrysum pamphylicum, Helichrysum orientale, Helichrysum noeanum (Asteraceae) are medicinal plants. For centuries, they have been used as tea in Turkey because of their medicinal properties. So far no scientific evidence has been found in a literature survey regarding the genotoxic effects of these plants. This work evaluated the genotoxic effects on human lymphocyte cultures induced by methanol extracts of these plants, assayed in different concentrations (0.01, 0.05, 0.1, 0.5 and 1 mg/mL). According to the results, Helichrysum noeanum, Helichrysum pamphylicum and Helichrysum sanguineum induced the formation of micronuclei and decreased the mitotic and replication indexes. Helichrysum orientale did not affect these parameters, whereas Helichrysum noeanum, Helichrysum pamphylicum and Helichrysum sanguineum were clearly genotoxic. They should therefore not be used freely in alternative medicine, although their antiproliferative activity may suggest antimitotic and anticarcinogenic properties. Helichrysum orientale could be used in alternative medicine.

  20. Chlorination of tramadol: Reaction kinetics, mechanism and genotoxicity evaluation.

    Science.gov (United States)

    Cheng, Hanyang; Song, Dean; Chang, Yangyang; Liu, Huijuan; Qu, Jiuhui

    2015-12-01

    Tramadol (TRA) is one of the most detected analgesics in environmental matrices, and it is of high significance to study the reactivity of TRA during chlorination considering its potential toxicity to the environment. The chlorine/TRA reaction is first order with respect to the TRA concentration, and a combination of first-order and second-order with respect to chlorine concentration. The pH dependence of the observed rate constants (kobs) showed that the TRA oxidation reactivity increased with increasing pH. kobs can be quantitatively described by considering all active species including Cl2, Cl2O and HOCl, and the individual rate constants of HOCl/TRA(0), HOCl/TRAH(+), Cl2/TRA and Cl2O/TRA reactions were calculated to be (2.61±0.29)×10(3)M(-1)s(-1), 14.73±4.17M(-1)s(-1), (3.93±0.34)×10(5)M(-1)s(-1) and (5.66±1.83)×10(6)M(-1)s(-1), respectively. Eleven degradation products were detected with UPLC-Q-TOF-MS, and the corresponding structures of eight products found under various pH conditions were proposed. The amine group was proposed to be the initial attack site under alkaline pH conditions, where reaction of the deprotonated amine group with HOCl is favorable. Under acidic and neutral pH conditions, however, two possible reaction pathways were proposed. One is an electrophilic substitution on the aromatic ring, and another is an electrophilic substitution on the nitrogen, leading to an N-chlorinated intermediate, which can be further oxidized. Finally, the SOS/umu test showed that the genotoxicity of TRA chlorination products increased with increasing dosage of chlorine, which was mostly attributed to the formation of some chlorine substitution products. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Genotoxicity of two heavy metal compounds: lead nitrate and cobalt chloride in Polychaete Perinereis cultrifera.

    Science.gov (United States)

    Singh, Nisha; Bhagat, Jacky; Ingole, Baban S

    2017-07-01

    The present study explores the in vivo and in vitro genotoxic effects of lead nitrate, [Pb(NO 3 ) 2 ] a recognized environmental pollutant and cobalt chloride (CoCl 2 ), an emerging environmental pollutant in polychaete Perinereis cultrifera using comet assay. Despite widespread occurrence and extensive industrial applications, no previous published reports on genotoxicity of these compounds are available in polychaete as detected by comet assay. Polychaetes were exposed in vivo to Pb(NO 3 ) 2 (0, 100, 500, and 1000 μg/l) and CoCl 2 (0, 100, 300, and 500 μg/l) for 5 days. At 100 μg/l Pb(NO 3 ) 2 concentration, tail DNA (TDNA) values in coelomocytes were increase by 1.16, 1.43, and 1.55-fold after day 1, day 3, and day 5, whereas, OTM showed 1.12, 2.33, and 2.10-fold increase in in vivo. Pb(NO 3 ) 2 showed a concentration and time-dependent genotoxicity whereas CoCl 2 showed a concentration-dependent genotoxicity in in vivo. A concentration-dependent increase in DNA damage was observed in in vitro studies for Pb(NO 3 ) 2 and CoCl 2 . DNA damage at 500 μg/L showed almost threefold increase in TDNA and approximately fourfold increase in OTM as compared to control in in vitro. Our studies suggest that Pb(NO 3 ) 2 and CoCl 2 have potential to cause genotoxic damage, with Pb(NO 3 ) 2 being more genotoxic in polychaete and should be used more carefully in industrial and other activities. Graphical abstract.

  2. Genotoxic pressure of vineyard pesticides in fish: field and mesocosm surveys.

    Science.gov (United States)

    Bony, S; Gillet, C; Bouchez, A; Margoum, C; Devaux, A

    2008-09-17

    The present study deals with the genotoxicity assessment of vineyard pesticides in fish exposed in the field or in mesocosm conditions. Primary DNA damage was quantified as strand breaks using the single cell gel electrophoresis assay (Comet assay) applied to fish erythrocytes. In a first experiment, a significant genotoxic effect was observed following an upstream-downstream gradient in early life stages of brown trout (Salmo trutta fario) exposed in the Morcille River contaminated by a mixture of vineyard pesticides during three consecutive years. The pronounced response in terms of DNA damage reported in the present study could argue for a high sensitivity of fish early life stage and/or a high level of exposure to genotoxic compounds in the Morcille River. This stresses the interest in using trout larvae incubated in sediment bed to assess genotoxic compounds in the field. In a second experiment, adult European topminnow (Phoxinus phoxinus) were exposed in water running through artificial channels to a mixture of diuron and azoxystrobin, two of the main pesticides detected in the Morcille watershed. As compared with the unexposed channel, a 3-5-fold increase in the DNA damage was observed in fish exposed to chronic environmental pesticide concentrations (1-2 microg L(-1) for diuron and 0.5-1 microg L(-1) for axoxystrobin). A single 6h pulse of pesticide (14 microg L(-1) of diuron and 7 microg L(-1) of azoxystrobin) was applied to simulate transiently elevated chemical concentrations in the river following storm conditions. It did not increase genotoxicity. After a 1-month recovery period, DNA damage in exposed fish erythrocytes recovered to unexposed level, suggesting possible involvement of both repair mechanisms and cellular turnover in this transient response. This work highlights that vineyard treatment by pesticides and in particular diuron and azoxystrobin can represent a genotoxic threat to fish from contaminated watershed rivers.

  3. In vitro and in vivo genotoxic evaluation of Bothrops moojeni snake venom.

    Science.gov (United States)

    Novak Zobiole, Nathalia; Caon, Thiago; Wildgrube Bertol, Jéssica; Pereira, Cintia Alves de Souza; Okubo, Brunna Mary; Moreno, Susana Elisa; Cardozo, Francielle Tramontini Gomes de Sousa

    2015-06-01

    Bothrops moojeni Hoge (Viperidae) venom is a complex mixture of compounds with therapeutic potential that has been included in the research and development of new drugs. Along with the biological activity, the pharmaceutical applicability of this venom depends on its toxicological profile. This study evaluates the cytotoxicity and genotoxicity of the Bothrops moojeni venom (BMV). The in vitro cytotoxicity and genotoxicity of a pooled sample of BMV was assessed by the MTT and Comet assay, respectively. Genotoxicity was also evaluated in vivo through the micronucleus assay. BMV displayed a 50% cytotoxic concentration (CC50) on Vero cells of 4.09 µg/mL. Vero cells treated with 4 µg/mL for 90 min and 6 h presented significant (p < 0.05, ANOVA/Newman-Keuls test) higher DNA damage than the negative control in the Comet assay. The lower DNA damage found after 6 h compared with the 90 min treatment suggests a DNA repair effect. Mice intraperitoneally treated with BMV at 10, 30, or 80 µg/animal presented significant genotoxicity (p < 0.05, ANOVA/Newman-Keuls test) in relation to the negative control after 24 h of treatment. Contrary to the in vitro results, no DNA repair seemed to occur in vivo up to 96 h post-venom inoculation at a dose of 30 µg/animal. The results show that BMV presents cyto- and genotoxicity depending on the concentration/dose used. These findings emphasize the importance of toxicological studies, including assessment of genotoxicity, in the biological activity research of BMV and/or in the development of BMV-derived products.

  4. Tungsten carbide-cobalt as a nanoparticulate reference positive control in in vitro genotoxicity assays.

    Science.gov (United States)

    Moche, Hélène; Chevalier, Dany; Barois, Nicolas; Lorge, Elisabeth; Claude, Nancy; Nesslany, Fabrice

    2014-01-01

    With the increasing human exposure to nanoparticles (NP), the evaluation of their genotoxic potential is of significant importance. However, relevance for NP of the routinely used in vitro genotoxicity assays is often questioned, and a nanoparticulate reference positive control would therefore constitute an important step to a better testing of NP, ensuring that test systems are really appropriate. In this study, we investigated the possibility of using tungsten carbide-cobalt (WC-Co) NP as reference positive control in in vitro genotoxicity assays, including 2 regulatory assays, the mouse lymphoma assay and the micronucleus assay, and in the Comet assay, recommended for the toxicological evaluation of nanomedicines by the French Agency of Human Health Products (Afssaps). Through these assays, we were able to study different genetic endpoints in 2 cell types commonly used in regulatory genotoxicity assays: the L5178Y mouse lymphoma cell line and primary cultures of human lymphocytes. Our results showed that the use of WC-Co NP as positive control in in vitro genotoxicity assays was conceivable, but that different parameters have to be considered, such as cell type and treatment schedule. L5178Y mouse lymphoma cells did not provide satisfactory results in the 3 performed tests. However, human lymphocytes were more sensitive to genotoxic effects induced by WC-Co NP, particularly after a 24-h treatment in the in vitro micronucleus assay and after a 4-h treatment in the in vitro Comet assay. Under such conditions, WC-Co could be used as a nanoparticulate reference positive control in these assays.

  5. Thinking Critically about Critical Thinking

    Science.gov (United States)

    Mulnix, Jennifer Wilson

    2012-01-01

    As a philosophy professor, one of my central goals is to teach students to think critically. However, one difficulty with determining whether critical thinking can be taught, or even measured, is that there is widespread disagreement over what critical thinking actually is. Here, I reflect on several conceptions of critical thinking, subjecting…

  6. Genotoxicity of the Musi River (Hyderabad, India) investigated with the VITOTOX test.

    Science.gov (United States)

    Vijayashree, B; Ahuja, Y R; Regniers, L; Rao, V; Verschaeve, L

    2005-01-01

    The bacterial VITOTOX genotoxicity test was used to screen water samples collected from three different stations along the banks of the river Musi, in Hyderabad, India. Water was collected at three stations that differed from each other in the nature of the surrounding industrial and other activities. A number of different pollutants were also measured in water, soil and air samples. The three stations were found highly polluted and different with regard to the genotoxicity and toxicity of their samples. These results demonstrate the need for further biological studies in this area to generate valuable data on genomic instability, risk assessment of cancer, and to provide avenues for risk management.

  7. Impacts of fullerene C60 and virgin olive oil on cadmium-induced genotoxicity in rats.

    Science.gov (United States)

    Aly, Fayza M; Kotb, Ahmed M; Haridy, Mohie A M; Hammad, Seddik

    2018-07-15

    Currently, cadmium is considered to be one of the major environmental pollutants. Environmentally, cadmium is released in various forms e.g. oxide, chloride and sulphide. The aim of the present study was to examine the genotoxic impact of fullerene nanoparticles C 60 (C 60 ) and virgin olive oil (VOO) on cadmium chloride (CdCl 2 )-induced genotoxicity in rats. To evaluate these effects on DNA damage and chromosomal frequency, 25 albino rats were randomly assigned to 5 groups (n=5 per group): Group 1 served as a control; Group 2 received a single intraperitoneal dose of CdCl 2 (3.5mg/kg); Group 3 animals were treated with C 60 (4mg/kg, orally) every other day for 20days; Group 4 received a single intraperitoneal dose of CdCl 2 (3.5mg/kg) and an oral dose of C 60 (4mg/kg); and Group 5 received a single intraperitoneal dose of CdCl 2 (3.5mg/kg) and oral doses of VOO every other day for 20 consecutive days. Genotoxic and anti-genotoxic effects of C 60 and VOO were evaluated in the liver, kidney and bone marrow using molecular and cytogenetic assays. As expected, CdCl 2 and C 60 administration was associated with band number alterations in both liver and kidney; however, C 60 pretreatment recovered to approximately basal number. Surprisingly, C 60 and VOO significantly attenuated the genotoxic effects caused by CdCl 2 in livers and kidneys. In bone marrow, in addition to a reduction in the chromosomal number, several chromosomal aberrations were caused by CdCl 2 . These chromosomal alterations were also reversed by C 60 and VOO. In conclusion, molecular and cytogenetic studies showed that C 60 and VOO exhibit anti-genotoxic agents against CdCl 2 -induced genotoxicity in rats. Further studies are needed to investigate the optimal conditions for potential biomedical applications of these anti-genotoxic agents. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. In vitro and in vivo genotoxicity of 1,3-butadiene and metabolites.

    OpenAIRE

    Arce, G T; Vincent, D R; Cunningham, M J; Choy, W N; Sarrif, A M

    1990-01-01

    1,3-Butadiene and two major genotoxic metabolites 3,4-epoxybutene (EB) and 1,2:3,4-diepoxybutane (DEB) were used as model compounds to determine if genetic toxicity findings in animal and human cells can aid in extrapolating animal toxicity data to man. Sister chromatid exchange (SCE) and micronucleus induction results indicated 1,3-butadiene was genotoxic in the bone marrow of the mouse but not the rat. This paralleled the chronic bioassays which showed mice to be more susceptible than rats ...

  9. DOE handbook: Design considerations

    International Nuclear Information System (INIS)

    1999-04-01

    The Design Considerations Handbook includes information and suggestions for the design of systems typical to nuclear facilities, information specific to various types of special facilities, and information useful to various design disciplines. The handbook is presented in two parts. Part 1, which addresses design considerations, includes two sections. The first addresses the design of systems typically used in nuclear facilities to control radiation or radioactive materials. Specifically, this part addresses the design of confinement systems and radiation protection and effluent monitoring systems. The second section of Part 1 addresses the design of special facilities (i.e., specific types of nonreactor nuclear facilities). The specific design considerations provided in this section were developed from review of DOE 6430.1A and are supplemented with specific suggestions and considerations from designers with experience designing and operating such facilities. Part 2 of the Design Considerations Handbook describes good practices and design principles that should be considered in specific design disciplines, such as mechanical systems and electrical systems. These good practices are based on specific experiences in the design of nuclear facilities by design engineers with related experience. This part of the Design Considerations Handbook contains five sections, each of which applies to a particular engineering discipline

  10. DOE handbook: Design considerations

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-04-01

    The Design Considerations Handbook includes information and suggestions for the design of systems typical to nuclear facilities, information specific to various types of special facilities, and information useful to various design disciplines. The handbook is presented in two parts. Part 1, which addresses design considerations, includes two sections. The first addresses the design of systems typically used in nuclear facilities to control radiation or radioactive materials. Specifically, this part addresses the design of confinement systems and radiation protection and effluent monitoring systems. The second section of Part 1 addresses the design of special facilities (i.e., specific types of nonreactor nuclear facilities). The specific design considerations provided in this section were developed from review of DOE 6430.1A and are supplemented with specific suggestions and considerations from designers with experience designing and operating such facilities. Part 2 of the Design Considerations Handbook describes good practices and design principles that should be considered in specific design disciplines, such as mechanical systems and electrical systems. These good practices are based on specific experiences in the design of nuclear facilities by design engineers with related experience. This part of the Design Considerations Handbook contains five sections, each of which applies to a particular engineering discipline.

  11. Critical Care

    Science.gov (United States)

    Critical care helps people with life-threatening injuries and illnesses. It might treat problems such as complications from surgery, ... attention by a team of specially-trained health care providers. Critical care usually takes place in an ...

  12. Current investigations into the genotoxicity of zinc oxide and silica nanoparticles in mammalian models in vitro and in vivo: carcinogenic/genotoxic potential, relevant mechanisms and biomarkers, artifacts, and limitations

    Directory of Open Access Journals (Sweden)

    Kwon JY

    2014-12-01

    Full Text Available Jee Young Kwon,1,* Preeyaporn Koedrith,2,* Young Rok Seo1 1Department of Life Science, Institute of Environmental Medicine, Dongguk University, Seoul, Republic of Korea; 2Faculty of Environment and Resource Studies, Mahidol University, Phuttamonthon District, NakhonPathom, Thailand *These authors contributed equally to this work and should be considered as co-first authors Abstract: Engineered nanoparticles (NPs are widely used in many sectors, such as food, medicine, military, and sport, but their unique characteristics may cause deleterious health effects. Close attention is being paid to metal NP genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying mechanisms remain to be elucidated. In this review, we address some metal and metal oxide NPs of interest and current genotoxicity tests in vitro and in vivo. Metal NPs can cause DNA damage such as chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. We also discuss several parameters that may affect genotoxic response, including physicochemical properties, widely used assays/end point tests, and experimental conditions. Although potential biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent findings in the literature render results inconclusive due to a variety of factors. Advantages and limitations related to different methods for investigating genotoxicity are described, and future directions and recommendations for better understanding genotoxic potential are addressed. Keywords: carcinogenicity, exposure assessment, genotoxicity, nanoparticles, risk evaluation

  13. Clinical Evaluation of Genotoxicity of In-office Bleaching.

    Science.gov (United States)

    Rezende, M; De Geus, J L; Loguercio, A D; Reis, A; Kossatz, D

    The aim of this study was to evaluate the genotoxicity of in-office bleaching with 35% hydrogen peroxide in epithelial cells from the gingival and lip tissues. Thirty volunteers with central incisors shade A1 or darker were selected for this study. The gingival tissue of the teeth to be bleached was isolated with a light-polymerized resin dam, and the 35% hydrogen peroxide gel was administered during three 15-minute applications over the course of the 45-minute application period. Two bleaching sessions with a one-week interval in between were performed. Exfoliated oral mucosa gingival epithelial cells and upper lip lining were collected at baseline and one month after the in-office dental bleaching. The scraped cells were placed on clean glass slides and smears were prepared. After staining with Giemsa solution, two blinded examiners performed cell and micronuclei counts under a 100× optical microscope. Tooth sensitivity was evaluated using the Visual Analogue Scale (VAS). Shade evaluation was recorded before and one month after the bleaching treatment with the value-oriented shade guide Vita Bleachedguide 3D-MASTER and the spectrophotometer Vita Easyshade. Data from the shade guide units and the micronuclei (MN) frequency were subjected to a Mann-Whitney test (α=0.05). The overall difference between before and one month after the bleaching treatment (ΔE and ΔSGU), absolute risk, and intensity of tooth sensitivity (TS) were calculated, as was the 95% confidence interval (CI). The frequency of MN was not increased after bleaching with 35% hydrogen peroxide in both study groups (p>0.05). The absolute risk of TS of the participants was 93% (95% CI, 79%-98%), with a mean VAS intensity of 5.7 ± 2.9 (95% CI, 4.6-6.8). Meaningful whitening was observed after bleaching. The change in shade guide units in the Bleachedguide 3D-MASTER was 2.3 ± 1.4. In terms of ΔE, the change in color was 7.7 ± 3.5. The in-office bleaching did not induce DNA damage to the gingival

  14. Epidermal stem cells response to radiative genotoxic stress

    International Nuclear Information System (INIS)

    Marie, Melanie

    2013-01-01

    Human skin is the first organ exposed to various environmental stresses, which requires the development by skin stem cells of specific mechanisms to protect themselves and to ensure tissue homeostasis. As stem cells are responsible for the maintenance of epidermis during individual lifetime, the preservation of genomic integrity in these cells is essential. My PhD aimed at exploring the mechanisms set up by epidermal stem cells in order to protect themselves from two genotoxic stresses, ionizing radiation (Gamma Rays) and ultraviolet radiation (UVB). To begin my PhD, I have taken part of the demonstration of protective mechanisms used by keratinocyte stem cells after ionizing radiation. It has been shown that these cells are able to rapidly repair most types of radiation-induced DNA damage. Furthermore, we demonstrated that this repair is activated by the fibroblast growth factor 2 (FGF2). In order to know if this protective mechanism is also operating in cutaneous carcinoma stem cells, we investigated the response to gamma Rays of carcinoma stem cells isolated from a human carcinoma cell line. As in normal keratinocyte stem cells, we demonstrated that cancer stem cells could rapidly repair radio-induced DNA damage. Furthermore, fibroblast growth factor 2 also mediates this repair, notably thanks to its nuclear isoforms. The second project of my PhD was to study human epidermal stem cells and progenitors responses to UVB radiation. Once cytometry and irradiation conditions were set up, the toxicity of UVB radiation has been evaluate in the primary cell model. We then characterized UVB photons effects on cell viability, proliferation and repair of DNA damage. This study allowed us to bring out that responses of stem cells and their progeny to UVB are different, notably at the level of part of their repair activity of DNA damage. Moreover, progenitors and stem cells transcriptomic responses after UVB irradiation have been study in order to analyze the global

  15. In situ assessment of genotoxic hazards of environmental pollution.

    Science.gov (United States)

    Sandhu, S S; Lower, W R

    1989-01-01

    The potential impact of the environmental pollutants on human health can be evaluated by the laboratory analysis of the environmental samples or by the measurement of the biological effects on indigenous populations and/or specific test organisms placed in the environment to be monitored. A canary in a cage, used by 19th century miners as a biological indicator for rising levels of toxic gases, is a classical example of in situ hazard identification. The induced toxic effects are often the result of synergistic and antagonistic interactions among various physical and chemical factors that are difficult to reproduce in the laboratory. Therefore, conceivably the biological effects measured on or near the impacted site have greater relevancy for hazard assessment to man than from the data derived from the environmental samples analyzed in the lab. The organisms most commonly employed for the assessment of mutagenicity under real-world conditions are: (1) flowering plants, (2) wild and captive mammals, and (3) aquatic vertebrates. Plant species such as Tradescantia paludosa, Zea mays, and Osmunda regalis have been used for monitoring ambient air quality around several major industrial cities in the U.S.A., nuclear power plants, and industrial waste sites, and also for the assessment of potential health effects of municipal sewage sludges. Domestic animals such as dogs can be used as sentinels to provide information on the effects of contaminants in the environment and have been used to a limited extent to evaluate the environmental influences on the occurrence of breast cancer and osteosarcoma. Cytogenetic analysis from feral and wild animals has been employed for assessing the health hazards and prioritizing the clean-up efforts at hazardous waste sites. Aquatic animals have been used more often than terrestrial animals or plants to identify and characterize the genotoxic effects of environmental pollution. Since 1970, a number of studies has been reported on the

  16. Critical early mission design considerations for lunar data systems architecture

    Science.gov (United States)

    Hei, Donald J., Jr.; Stephens, Elaine

    1992-01-01

    This paper outlines recent early mission design activites for a lunar data systems architecture. Each major functional element is shown to be strikingly similar when viewed in a common reference system. While this similarity probably deviates with lower levels of decomposition, the sub-functions can always be arranged into similar and dissimilar categories. Similar functions can be implemented as objects - implemented once and reused several times like today's advanced integrated circuits. This approach to mission data systems, applied to other NASA programs, may result in substantial agency implementation and maintenance savings. In today's zero-sum-game budgetary environment, this approach could help to enable a lunar exploration program in the next decade. Several early mission studies leading to such an object-oriented data systems design are recommended.

  17. The Selves of Educational Psychology: Conceptions, Contexts, and Critical Considerations

    Science.gov (United States)

    Martin, Jack

    2007-01-01

    This article begins with an interpretation and description of conceptions of selfhood that are assumed in educational psychologists' programs of theory, research, and practice in the area of student self-development. Three underlying conceptions of the self are considered: (a) the expressive self (found mostly in research and theory on self-esteem…

  18. Assessing genotoxic effects in fish from a marine protected area influenced by former mining activities and other stressors

    International Nuclear Information System (INIS)

    Gusso-Choueri, Paloma Kachel; Choueri, Rodrigo Brasil; Santos, Gustavo Souza; Seraphim de Araújo, Giuliana; Feitosa Cruz, Ana Carolina

    2016-01-01

    The goal of the current study was to evaluate different genotoxicity tools in order to assess a marine protected area (MPA) affected by former mining activities and urban settlements. A catfish (Cathorops spixii) was analyzed for genotoxic effects at the (i) molecular and at the (ii) chromosomal levels. Through factor analysis, genotoxicity was found to be linked to levels of metals bioaccumulated and PAH metabolites in the bile. Micronucleus and nuclear alteration were less vulnerable to the effects of confounding factors in mildly contaminated areas since they were more frequently associated with bioaccumulated metals than the DNA analysis. The different genotoxicity responses allowed for the identification of sources of pollution in the MPA. This approach was important for detecting environmental risks related to genotoxic contaminants in a mildly contaminated MPA. -- Highlights: •We assessed genotoxicity and bioaccumulation in catfish from a marine protected area. •The area is under the influence of past mining activities and urban settlements. •Cellular level responses were highly associated with body burdens of metals and As. •Responses at the molecular level were less associated with body burdens. •Genotoxicity in different organs helped identify pollution sources in MPA.

  19. Induction of micronuclei by 2-hydroxypyridine in water and elimination of solution genotoxicity by UVC (254 nm) photolysis

    International Nuclear Information System (INIS)

    Skoutelis, Charalambos G.; Vlastos, Dimitris; Kortsinidou, Marianna C.; Theodoridis, Ioannis T.; Papadaki, Maria I.

    2011-01-01

    Highlights: ► 2-Hydroxypyridine (2-HPY) is the major metabolite of 2-halogenated pyridines photolysis. ► We examine the genotoxicity of 2-HPY in cultured human lymphocytes applying the micronucleus assay. ► 2-HPY was found to be genotoxic. ► Aqueous solutions of 2-HPY were irradiated by UV at 254 nm. ► Solution genotoxicity can be completely removed after prolonged phototreatment. - Abstract: 2-Hydroxypyridine (2-HPY) is a major first-stage product formed upon the photolytic destruction of 2-halogenated pyridines. Genotoxicity of 2-HPY in water was studied as a function of concentration. Aqueous solutions of 2-HPY were irradiated by ultraviolet (UV) at 254 nm. 2-HPY concentration, solution total organic carbon (TOC) concentration and solution genotoxicity were measured as a function of treatment time and their profile as a function of time is presented in this work. 2-HPY was found to be genotoxic at all concentrations in the range of 5–400 μg ml −1 . 2-HPY mineralises completely upon prolonged UV irradiation. All untreated and irradiated solution samples, taken at different photo-treatment times, were tested in cultured human lymphocytes applying the cytokinesis block micronucleus (CBMN) assay. The genotoxicity of the solution was reduced near to the control level after prolonged UV irradiation.

  20. Cytotoxicity and genotoxicity of intravitreal adalimumab administration in rabbit retinal cells

    Directory of Open Access Journals (Sweden)

    Álcio Coutinho de Paula

    2015-04-01

    Full Text Available Purpose: To assess the cytotoxicity and genotoxicity of intravitreal adalimumab treatment in an animal experimental model using cytological and molecular techniques. Methods: Eighteen rabbits were randomly assigned to three groups: control, adalimumab treatment, and placebo. Cytotoxicity on retinal cells was evaluated using flow cytometry assays to determine the level of apoptosis and necrosis. Genotoxicity was evaluated by comet assays to assess DNA damage, and quantitative real-time polymerase chain reaction (qPCR was used to evaluate expression of apoptosis-inducing caspases (8 and 3. Results: No cytotoxicity or genotoxicity was observed in any of the two treatment groups (adalimumab and placebo following intravitreal administration compared with the control group. Flow cytometry analysis revealed that more than 90% of the cells were viable, and only a low proportion of retinal cells presented apoptotic (~10% or necrotic (<1% activity across all groups. Molecular damage was also low with a maximum of 6.4% DNA degradation observed in the comet assays. In addition, no increase in gene expression of apoptosis-inducing caspases was observed on retinal cells by qPCR in both the adalimumab and placebo groups compared with the control group. Conclusion: The use of adalimumab resulted in no detectable cytotoxicity or genotoxicity on retinal cells for up to 60 days upon administration. These results therefore indicate that adalimumab may be a safe option for intravitreal application to treat ocular inflammatory diseases in which TNF-α is involved.

  1. Genotoxicity study of an experimental beverage made with quinua, kiwicha and kañiwa

    Directory of Open Access Journals (Sweden)

    Francia D.P. Huaman

    2014-12-01

    Full Text Available Genotoxic evaluation is an important step for a product that is aimed for human consumption. A beverage composed of pseudocereals with highly nutritious elements like quinua (Chenopodium quinoa Willd., kiwicha (Amaranthus caudatus L. and kañiwa (Chenopodium pallidicaule Aellen was prepared to reduce lipid contents in a group of volunteers. The objective of the present study is to evaluate the genotoxic potential of an experimental beverage using two in vitro tests that have been validated by international agencies. For the Ames test, two strains of Salmonella typhimurium (TA98 and TA100 with and without microsomal fraction (S9 were used. Four doses of the beverage were tested and also a possible protective effect (same four doses of beverage added to plates with mutagens. Cultures of binucleated lymphocytes and five doses of the beverage were used for the micronucleus test. Both Ames and the micronucleus tests showed the beverage has not genotoxic effect in all tested doses. However, in evaluating the possible protective effect of the beverage, it would be evident that on the contrary, the mutagenic effect of mutagens used for each strain is enhanced. These results suggest that additional tests should be performed to check the genotoxic potential of this beverage before consumption.

  2. Induction of cytotoxic and genotoxic effects of Guandu River waters in the Allium cepa system

    Directory of Open Access Journals (Sweden)

    Jennifer Vieira Gomes

    2015-01-01

    Full Text Available The Guandu River is the main source of water supply for the metropolitan region of Rio de Janeiro and has been facing serious environmental problems due to increasing population and industrial pollution, as well as the presence of polluted tributaries. This study analyzed the cytotoxic and genotoxic potential of the Guandu River’s waters, through the use of the Allium cepa test system. Collection points were chosen at the greatest confluences of pollutant sources. The sampling included two different seasons: the rainy season (January and February and the dry season (June and July. The analyses of 5000 cells per treatment showed that all the points studied had some degree of cytotoxicity and/or genotoxicity. Two sampling locations, which receive major influxes from the polluted waters of the Poços/Queimados and Cabuçu/Ipiranga Rivers, stood out for the strong presence of micronuclei, sticky chromosomes, mitotic spindle abnormalities, necrotic cells and nucleolar changes compared to the negative control. At least two locations also found changes in the mitotic index. The existence of variations in the number of cytotoxic and genotoxic changes between periods of rain and drought indicates that the cytotoxic and genotoxic potential of the water pollutants varies according to time, depending on the discharges of the tributary rivers and the increase of contaminated effluents. The results highlight the importance of bio-monitoring to assist managers in the control of effluent discharge.

  3. Correlation between serum anyloid a low density lipoprotein and genotoxicity in smokers

    International Nuclear Information System (INIS)

    Jamil, A.; Rashid, A.; Majeed, A.; Naveed, A.K.

    2018-01-01

    Objective:To investigate the relation between serum amyloid A-low density lipoprotein (SAA-LDL) and genotoxicity in smokers. Study Design:An experimental study. Place and Duration of Study:Army Medical College, Rawalpindi and National Institute of Health (NIH), Islamabad, from June 2014 to February 2015. Methodology:Seventy healthy Sprague Dawley rats were purchased from NIH and exposed to cigarette smoke in smoke chamber for three months. Blood samples were drawn from each rat at the end of the study period. SAA-LDL was determined by enzyme-linked immunosorbent assay (ELISA). Genotoxicity was assessed by cytokinesis block micronucleus (CBMN) assay. Pearson correlation was used to find correlation between SAA-LDL and genotoxicity. Results:Strong positive correlation was found between SAA-LDL and micronuclei frequency in smoke-exposed rats (r=0.799, N=70, p <0.01). Conclusion:Statistically significant strong positive correlation between SAA-LDL and genotoxicity in smoke-exposed rats shows that changes in one is associated with changes in other and vice versa. (author)

  4. Modulation of mitomycin C-induced genotoxicity by acetyl- and thio- analogues of salicylic acid.

    Science.gov (United States)

    Pawar, Amol Ashok; Vikram, Ajit; Tripathi, Durga Nand; Padmanabhan, Shweta; Ramarao, Poduri; Jena, Gopabandhu

    2009-01-01

    Recent reports regarding acetylsalicylic acid (ASA) and its metabolites suggest suppressive effects against mitomycin C (MMC)-induced genotoxicity in a mice chromosomal aberration assay. Keeping this in mind, the potential anti-genotoxic effect of the thio-analogue of salicylic acid namely thio-salicylic acid (TSA) was speculated upon. The present study investigated and compared the anti-genotoxic potential of ASA and TSA. The study was performed in male swiss mice (20+/-2 g) using single-cell gel electrophoresis and a peripheral blood micronucleus assay. ASA and TSA (5, 10 or 20 mg/kg) were administered 15 minutes after MMC (1 mg/kg) once daily for 3 or 7 days. Both ASA and TSA significantly decreased the DNA damage induced by MMC as indicated by a decrease in the comet parameters in bone marrow cells and decreased frequencies of micronucleated reticulocytes in peripheral blood. The results clearly demonstrate the anti-genotoxic potential of ASA and TSA.

  5. Increasing fish consumption does not affect genotoxicity markers in the colon in an intervention study

    NARCIS (Netherlands)

    Pot, G.K.; Habermann, N.; Majsak-Newman, G.; Harvey, L.J.; Geelen, A.; Przybylska-Philips, P.; Nagengast, F.M.; Witteman, B.J.M.; van de Meeberg, P.C.; Hart, A.R.; Schaafsma, G.; Hooiveld, G.; Glei, M.; Lund, E.K.; Pool-Zobel, B.; Kampman, E.

    2010-01-01

    Observational studies suggest that fish consumption is associated with a decreased colorectal cancer (CRC) risk. A possible mechanism by which fish could reduce CRC risk is by decreasing colonic genotoxicity. However, concerns have also been raised over the levels of toxic compounds found in mainly

  6. Effect of upgraded diesel fuels and oxidation catalysts on emission properties, especially PAH and genotoxicity

    DEFF Research Database (Denmark)

    Johansen, Keld; Gabrielsson, Pär; Stavnsbjerg, Peter

    1997-01-01

    in an engine test bench and a full ECE R49 13 mode test was performed and 2) a VW GOLF 1.6 l engine was mounted in a car and a full transient FTP-75 test was performed. Regulated emissions and unregulated emissions as SOF, sulphur, nitrate, PAH in PM plus vapour phase were measured. Genotoxic activity...

  7. Genotoxicity evaluation of dental restoration nanocomposite using comet assay and chromosome aberration test

    International Nuclear Information System (INIS)

    Musa, Marahaini; Ponnuraj, Kannan Thirumulu; Mohamad, Dasmawati; Rahman, Ismail Ab

    2013-01-01

    Nanocomposite is used as a dental filling to restore the affected tooth, especially in dental caries. The dental nanocomposite (KelFil) for tooth restoration used in this study was produced by the School of Dental Sciences, Universiti Sains Malaysia, Malaysia and is incorporated with monodispersed, spherical nanosilica fillers. The aim of the study was to determine the genotoxic effect of KelFil using in vitro genotoxicity tests. The cytotoxicity and genotoxicity of KelFil was evaluated using MTT assay, comet assay and chromosome aberration tests with or without the addition of a metabolic activation system (S9 mix), using the human lung fibroblast cell line (MRC-5). Concurrent negative and positive controls were included. In the comet assay, no comet formation was found in the KelFil groups. There was a significant difference in tail moment between KelFil groups and positive control (p < 0.05). Similarly, no significant aberrations in chromosomes were noticed in KelFil groups. The mitotic indices of treatment groups and negative control were significantly different from positive controls. Hence, it can be concluded that the locally produced dental restoration nanocomposite (KelFil) is non-genotoxic under the present test conditions. (paper)

  8. Aporrectodea caliginosa, a suitable earthworm species for field based genotoxicity assessment?

    International Nuclear Information System (INIS)

    Klobucar, Goeran I.V.; Stambuk, Anamaria; Srut, Maja; Husnjak, Ivana; Merkas, Martina; Traven, Luka; Cvetkovic, Zelimira

    2011-01-01

    There is a growing interest for the application of biomakers to field-collected earthworms. Therefore we have evaluated the usability of native populations of endogeic, widely distributed earthworm Aporrectodea caliginosa in the assessment of soil genotoxicity using the Comet assay. Validation of the Comet assay on earthworm coelomocytes has been established using commercially available Eisenia fetida exposed to copper, cadmium, and pentachlorophenol, along with A. caliginosa exposed to copper in a filter paper contact test. Neutral red retention time (NRRT) assay was conducted on copper exposed and field-collected earthworms. Significant DNA and lysosomal damage was measured using Comet and NRRT assays in native populations of A. caliginosa sampled from the polluted soils in the urban area in comparison to the earthworms from the reference site. The results of this study confirm the employment of A. caliginosa as a suitable species for the in situ soil toxicity and genotoxicity field surveys. - Research highlights: → Native A. caliginosa has shown significant biological effect measured by the Comet and NRRT assays. → The Comet assay on A. caliginosa and E. fetida has shown to be of similar sensitivity as the NRRT assay. → A. caliginosa is a suitable species for the in situ soil toxicity and genotoxicity field surveys. - Native populations of endogeic earthworm Aporrectodea caliginosa can be successfully applied in the genotoxicity field surveys using Comet assay.

  9. Detection of genotoxic effects of drinking water disinfection by-products using Vicia faba bioassay.

    Science.gov (United States)

    Hu, Yu; Tan, Li; Zhang, Shao-Hui; Zuo, Yu-Ting; Han, Xue; Liu, Na; Lu, Wen-Qing; Liu, Ai-Lin

    2017-01-01

    Plant-based bioassays have gained wide use among the toxicological and/or ecotoxicological assessment procedures because of their simplicity, sensitivity, low cost, and reliability. The present study describes the use of Vicia faba (V. faba) micronucleus (MN) test and V. faba comet assay in the evaluation of the genotoxic potential of disinfection by-products (DBPs) commonly found in chlorine-disinfected drinking water. Five haloacetic acids and three halogenated acetonitriles were chosen as representatives of DBPs in this study because they are of potentially great public health risk. Results of the MN test indicated that monochloroacetic acid (MCA), monobromoacetic acid (MBA), dichloroacetic acid (DCA), dibromoacetic acid (DBA), trichloroacetic acid (TCA), and trichloroacetonitrile (TCAN) caused a statistically significant increase in MN frequency in V. faba root tip cells. However, no genotoxic response was observed for dichloroacetonitrile (DCAN) and dibromoacetonitrile (DBAN). Results of the comet assay showed that all tested DBPs induced a statistically significant increase in genomic DNA damage to V. faba root tip cells. On considering the capacity to detect genomic damage of a different nature, we suggest that a combination of V. faba MN test and V. faba comet assay is a useful tool for the detection of genotoxic effects of DBPs. It is worthy of assessing the feasibility of using V. faba comet assay combined with V. faba MN test to screen for the genotoxic activity of chlorinated drinking water in future work.

  10. Cytotoxic and genotoxic potential of food-borne nitriles in a liver in vitro model

    Science.gov (United States)

    Kupke, Franziska; Herz, Corinna; Hanschen, Franziska S.; Platz, Stefanie; Odongo, Grace A.; Helmig, Simone; Bartolomé Rodríguez, María M.; Schreiner, Monika; Rohn, Sascha; Lamy, Evelyn

    2016-01-01

    Isothiocyanates are the most intensively studied breakdown products of glucosinolates from Brassica plants and well recognized for their pleiotropic effects against cancer but also for their genotoxic potential. However, knowledge about the bioactivity of glucosinolate-borne nitriles in foods is very poor. As determined by GC-MS, broccoli glucosinolates mainly degrade to nitriles as breakdown products. The cytotoxicity of nitriles in human HepG2 cells and primary murine hepatocytes was marginal as compared to isothiocyanates. Toxicity of nitriles was not enhanced in CYP2E1-overexpressing HepG2 cells. In contrast, the genotoxic potential of nitriles was found to be comparable to isothiocyanates. DNA damage was persistent over a certain time period and CYP2E1-overexpression further increased the genotoxic potential of the nitriles. Based on actual in vitro data, no indications are given that food-borne nitriles could be relevant for cancer prevention, but could pose a certain genotoxic risk under conditions relevant for food consumption. PMID:27883018

  11. Formation of genotoxic compounds by medium pressure ultra violet treatment of nitrate rich water

    NARCIS (Netherlands)

    Martijn, A.J.; Boersma, M.G.; Vervoort, Jacques; Rietjens, I.; Kruithof, J.C.

    2014-01-01

    Genotoxic compounds were produced by full-scale medium pressure (MP) ultraviolet hydrogen peroxide (UV/H2O2) treatment of nitrate-rich pretreated surface water. It was hypothesized that this formation was caused by the reaction of nitrate photolysis intermediates with natural organic matter (NOM).

  12. Genotoxic and teratogenic potential of marine sediment extracts investigated with comet assay and zebrafish test

    International Nuclear Information System (INIS)

    Kammann, Ulrike; Biselli, Scarlett; Huehnerfuss, Heinrich; Reineke, Ninja; Theobald, Norbert; Vobach, Michael; Wosniok, Werner

    2004-01-01

    Organic extracts of marine sediments from the North Sea and the Baltic Sea were investigated with two toxicity assays. The comet assay based on the fish cell line Epithelioma papulosum cyprini (EPC) was applied to determine the genotoxic potential; zebrafish embryos (Danio rerio) were used to quantify the teratogenic potential of the samples. EC 50 values were calculated from dose-response curves for both test systems. Highest teratogenic and genotoxic effects normalised to total organic carbon (TOC) content were detected in sediment samples of different origins. Polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) are not likely to be the causes of the observed effects, as demonstrated by a two-step fractionation procedure of selected extracts. The toxic potential was more pronounced in fractions having polarity higher than those possessed by PAHs and PCBs. The suitability of the two in vitro test systems for assessing genotoxic and teratogenic effects of marine sediment extracts could be demonstrated. - Capsule: In vitro toxicity assays are used to assess genotoxic and teratogenic effects of environmental extracts

  13. In vivo genotoxicity evaluation of an artichoke (Cynara scolymus L.) aqueous extract.

    Science.gov (United States)

    Zan, Meriele A; Ferraz, Alexandre B F; Richter, Marc F; Picada, Jaqueline N; de Andrade, Heloisa H R; Lehmann, Mauricio; Dihl, Rafael R; Nunes, Emilene; Semedo, Juliane; Da Silva, Juliana

    2013-02-01

    The Cynara scolymus (artichoke) is widely consumed as tea or food and shows important therapeutic properties. However, few studies have assessed the possible toxic effects of artichoke extracts. This study evaluates genotoxic and mutagenic activities of artichoke leaf aqueous extract in mice using the comet assay and the micronucleus test. Leaf extracts were given by gavage (500 mg/kg, 1000 mg/kg, and 2000 mg/kg) for 3 consecutive days. Extract composition was investigated using phytochemical screening and high-performance liquid chromatography (HPLC). In addition, antioxidant capacity was analyzed through the diphenyl-picrylhydrazyl (DPPH) and xanthine oxidase assay. Phytochemical screening detected the presence of phenolic compounds, flavonoids, and saponins. HPLC analyses indicated the presence of chlorogenic acid, caffeic acid, isoquercetrin, and rutin. Extracts showed a dose-dependent free radical scavenging effect of DPPH and an inhibitory effect of xanthine oxidase. The genotoxic results showed that leaf extracts did not increase micronuclei in peripheral blood cells. Compared to the control group, a significant increase in comet assay values was observed only in bone marrow of group treated with 2000 mg/kg, the highest dose tested, indicating that artichoke tea should be consumed with moderation. This is the first report of in vivo mutagenic and genotoxic evaluation with C. scolymus. The present study revealed leaf aqueous extract from artichoke shows lack of mutagenicity in vivo, and low genotoxicity and antioxidant activity; indicating that artichoke tea should be consumed with moderation. © 2013 Institute of Food Technologists®

  14. DNA repair and cyclin D1 polymorphisms and styrene-induced genotoxicity and immunotoxicity

    Czech Academy of Sciences Publication Activity Database

    Kuricová, Miroslava; Naccarati, Alessio; Kumar, R.; Koskinen, M.; Sanyal, S.; Dušinská, M.; Tulinská, J.; Vodičková, Ludmila; Lisková, A.; Jahnová, E.; Fuortes, L.; Haufroid, V.; Hemminki, K.; Vodička, Pavel

    2005-01-01

    Roč. 207, - (2005), S302-S309 ISSN 0041-008X R&D Projects: GA ČR GA310/03/0437 Institutional research plan: CEZ:AV0Z5039906 Keywords : styrene genotoxicity * immunotoxicity Subject RIV: FM - Hygiene Impact factor: 3.148, year: 2005

  15. Aporrectodea caliginosa, a suitable earthworm species for field based genotoxicity assessment?

    Energy Technology Data Exchange (ETDEWEB)

    Klobucar, Goeran I.V., E-mail: gklobuca@zg.biol.pmf.hr [Department of Zoology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, 10000 Zagreb (Croatia); Stambuk, Anamaria; Srut, Maja [Department of Zoology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, 10000 Zagreb (Croatia); Husnjak, Ivana [Ministry of Environmental Protection, Physical Planning and Construction, Ulica Republike Austrije 14, Zagreb (Croatia); Merkas, Martina [Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Salata 12, 10000 Zagreb (Croatia); Traven, Luka [Department of Environmental Medicine, Medical Faculty, University of Rijeka, Brace Branchetta 20a, 51000 Rijeka (Croatia); Teaching Institute of Public Health of the Primorsko-goranska County, Kresimirova 52a, 51000 Rijeka (Croatia); Cvetkovic, Zelimira [Department of Ecology, Institute of Public Health, Mirogojska c. 16, 10000 Zagreb (Croatia)

    2011-04-15

    There is a growing interest for the application of biomakers to field-collected earthworms. Therefore we have evaluated the usability of native populations of endogeic, widely distributed earthworm Aporrectodea caliginosa in the assessment of soil genotoxicity using the Comet assay. Validation of the Comet assay on earthworm coelomocytes has been established using commercially available Eisenia fetida exposed to copper, cadmium, and pentachlorophenol, along with A. caliginosa exposed to copper in a filter paper contact test. Neutral red retention time (NRRT) assay was conducted on copper exposed and field-collected earthworms. Significant DNA and lysosomal damage was measured using Comet and NRRT assays in native populations of A. caliginosa sampled from the polluted soils in the urban area in comparison to the earthworms from the reference site. The results of this study confirm the employment of A. caliginosa as a suitable species for the in situ soil toxicity and genotoxicity field surveys. - Research highlights: > Native A. caliginosa has shown significant biological effect measured by the Comet and NRRT assays. > The Comet assay on A. caliginosa and E. fetida has shown to be of similar sensitivity as the NRRT assay. > A. caliginosa is a suitable species for the in situ soil toxicity and genotoxicity field surveys. - Native populations of endogeic earthworm Aporrectodea caliginosa can be successfully applied in the genotoxicity field surveys using Comet assay.

  16. Measurement of DNA integrity in marine gastropods as biomarker of genotoxicity

    Digital Repository Service at National Institute of Oceanography (India)

    Sarkar, A.; Vashistha, D.; Gupta, N.; Malik, K.; Gaitonde, D.C.S.

    to identify the hot spot of pollution due to genotoxic compounds, the DNA damage was measured in terms of the loss of DNA integrity in marine gastropods due to the occurrence of DNA strand breaks following the technique of time dependent partially alkaline...

  17. Way forward in case of a false positive in vitro genotoxicity result for a cosmetic substance?

    Science.gov (United States)

    Doktorova, Tatyana Y; Ates, Gamze; Vinken, Mathieu; Vanhaecke, Tamara; Rogiers, Vera

    2014-02-01

    The currently used regulatory in vitro mutagenicity/genotoxicity test battery has a high sensitivity for detecting genotoxicants, but it suffers from a large number of irrelevant positive results (i.e. low specificity) thereby imposing the need for additional follow-up by in vitro and/or in vivo genotoxicity tests. This could have a major impact on the cosmetic industry in Europe, seen the imposed animal testing and marketing bans on cosmetics and their ingredients. Afflicted, but safe substances could therefore be lost. Using the example of triclosan, a cosmetic preservative, we describe here the potential applicability of a human toxicogenomics-based in vitro assay as a potential mechanistically based follow-up test for positive in vitro genotoxicity results. Triclosan shows a positive in vitro chromosomal aberration test, but is negative during in vivo follow-up tests. Toxicogenomics analysis unequivocally shows that triclosan is identified as a compound acting through non-DNA reactive mechanisms. This proof-of-principle study illustrates the potential of genome-wide transcriptomics data in combination with in vitro experimentation as a possible weight-of-evidence follow-up approach for de-risking a positive outcome in a standard mutagenicity/genotoxicity battery. As such a substantial number of cosmetic compounds wrongly identified as genotoxicants could be saved for the future. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Physicochemical characteristics, mutagenicity and genotoxicity of airborne particles under industrial and rural influences in Northern Lebanon.

    Science.gov (United States)

    Melki, Pamela N; Ledoux, Frédéric; Aouad, Samer; Billet, Sylvain; El Khoury, Bilal; Landkocz, Yann; Abdel-Massih, Roula M; Courcot, Dominique

    2017-08-01

    In this work, the main objectives were to assess the mutagenic and genotoxic effects of fine particulate matter collected in an industrial influenced site in comparison with a non-industrial influenced one (rural site) and to relate the particulate matter (PM) composition to the observed genotoxic effects. At the industrial influenced site, higher concentrations of phosphates, trace metals, and polycyclic aromatic hydrocarbons (PAHs) in particles could be related to the contributions of quarries, fertilizer producer, cement plants, and tires burning. Gasoline and diesel combustion contributions were evidenced in particles collected at both sites. Particles collected under industrial influence showed a higher mutagenic potential on three tested strains of Salmonella typhimurium (TA98, YG1041, and TA102), and especially on the YG1041, compared to particles from the rural site. Furthermore, only particles collected in the vicinity of the industrial site showed a tendency to activate the SOS responses in Escherichia coli PQ37, which is indicative of DNA damage as a result of exposure of the bacteria cells to the action of mutagenic samples. The mutagenicity and genotoxicity of the industrial PM 2.5-0.3 particulates may be attributed to its composition especially in organic compounds. This study showed that proximity of industries can affect local PM composition as well as PM genotoxic and mutagenic potential.

  19. Assessing the genotoxicity of urban air pollutants using two in situ plant bioassays

    Energy Technology Data Exchange (ETDEWEB)

    Villarini, M.; Fatigoni, C.; Dominici, L.; Maestri, S. [Department of Medical-Surgical Specialties and Public Health, University of Perugia, I-06126 (Italy); Ederli, L.; Pasqualini, S. [Department of Applied Biology, University of Perugia, I-06121 (Italy); Monarca, S. [Department of Medical-Surgical Specialties and Public Health, University of Perugia, I-06126 (Italy); Moretti, M., E-mail: massimo.moretti@unipg.i [Department of Medical-Surgical Specialties and Public Health, University of Perugia, I-06126 (Italy)

    2009-12-15

    Genotoxicity of urban air has been analysed almost exclusively in airborne particulates. We monitored the genotoxic effects of airborne pollutants in the urban air of Perugia (Central Italy). Two plant bioindicators with different genetic endpoints were used: micronuclei in meiotic pollen mother cells using Tradescantia-micronucleus bioassay (Trad-MCN) and DNA damage in nuclei of Nicotiana tabacum leaves using comet assay (Nicotiana-comet). Buds of Tradescantia clone no. 4430 and young N. tabacum cv. Xanthi plants were exposed for 24 h at three sites with different pollution levels. One control site (indoor control) was also used. The two bioassays showed different sensitivities toward urban pollutants: Trad-MCN assay was the most sensitive, but DNA damage in N. tabacum showed a better correlation with the pollutant concentrations. In situ biomonitoring of airborne genotoxins using higher plants combined with chemical analysis is thus recommended for characterizing genotoxicity of urban air. - Plant bioassays used to explore in situ the correlation between air pollution and genotoxicity.

  20. Exposure to sorbitol during lactation causes metabolic alterations and genotoxic effects in rat offspring.

    Science.gov (United States)

    Cardoso, Felipe S; Araujo-Lima, Carlos F; Aiub, Claudia A F; Felzenszwalb, Israel

    2016-10-17

    Sorbitol is a polyol used by the food industry as a sweetener. Women are consuming diet and light products containing sorbitol during pregnancy and in the postnatal period to prevent themselves from excessive weight gain and maintain a slim body. Although there is no evidence for the genotoxicity of sorbitol in the perinatal period, this study focused on evaluating the effects of the maternal intake of sorbitol on the biochemical and toxicological parameters of lactating Wistar rat offspring after 14days of mother-to-offspring exposure. A dose-dependent reduction of offspring length was observed. An increase in sorbitol levels determined in the milk was also observed. However, we detected an inverse relationship between the exposition dose in milk fructose and triacylglycerols concentrations. There was an increase in the plasmatic levels of ALT, AST and LDLc and a decrease in proteins, cholesterol and glucose levels in the offspring. Sorbitol exposure caused hepatocyte genotoxicity, including micronuclei induction. Maternal sorbitol intake induced myelotoxicity and myelosuppression in their offspring. The Comet assay of the blood cells detected a dose-dependent genotoxic response within the sorbitol-exposed offspring. According to our results, sorbitol is able to induce important metabolic alterations and genotoxic responses in the exposed offspring. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Genotoxicity detected in wild mice living in a highly polluted wetland area in south western Spain

    Energy Technology Data Exchange (ETDEWEB)

    Mateos, Santiago; Daza, Paula; Dominguez, Inmaculada; Cardenas, Jose Antonio [University of Seville, Department of Cell Biology, Faculty of Biology, Avenida de la Reina Mercedes no 6, E-41012 Seville (Spain); Cortes, Felipe [University of Seville, Department of Cell Biology, Faculty of Biology, Avenida de la Reina Mercedes no 6, E-41012 Seville (Spain)], E-mail: cortes@us.es

    2008-06-15

    A field study was carried out in the south of the Iberian Peninsula in an industrial area in the neighbourhood of Huelva city, SW Spain, and in a natural area (Donana National Park) for comparison, to estimate the genetic risk induced by environmental pollution in wild mice. Genotoxic effects in a sentinel organism, the Algerian mice (Mus spretus) free living in the industrial area were compared with animals of the same species living in the natural protected area. The single cell gel electrophoresis, or Comet assay, was performed as a genotoxicity test in peripheral blood of mice. Our results clearly show that mice free living in the contaminated area bear a high burden of genetic damage as compared with control individuals. The results suggest that the assessing of genotoxicity levels by the Comet assay in wild mice can be used as a valuable test in pollution monitoring and environmental conservation. - We have found an increased genotoxic damage in wild mice in a highly polluted area from industry, mining and agriculture in SW Spain, as assessed by the Comet assay.

  2. Synergistic effect of Gentiana lutea L. on methyl methanesulfonate genotoxicity in the Drosophila wing spot test.

    Science.gov (United States)

    Patenković, Aleksandra; Stamenković-Radak, Marina; Nikolić, Dragana; Marković, Tamara; Anđelković, Marko

    2013-03-27

    Gentiana lutea L., the yellow gentian, is herb known for its pharmacological properties, with a long tradition of use for the treatment of a variety of diseases including the use as a remedy for digestion, also in food products and in bitter beverages. The aim of the present study is to evaluate, for the first time, genotoxicity of gentian alone, and its antigenotoxicity against methyl methanesulfonate (MMS). The water infusion of the underground part of gentian were evaluated in vivo using the Drosophila wing spot test, at the dose commonly used in traditional medicine. For antigenotoxic study two types of treatment with gentian and MMS were performed: chronic co-treatment, as well as post-treatment with gentian after acute exposure with MMS. Water infusion of gentian alone did not exhibit genotoxicity. The results of co- and post-treatment experiments with gentian show that gentian enhanced the frequency of mutant clones over the values obtained with MMS alone, instead of reducing the genotoxicity of MMS, for 22.64% and 27.13% respectively. This result suggests a synergism of gentian with MMS, and indicates that water infusion of gentian used in traditional medicine may have particular effects with regard to genotoxicity indicating careful use. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Cytotoxic and genotoxic studies of essential oil from Rosa damascene Mill., Kashan, Iran.

    Science.gov (United States)

    Shokrzadeh, Mohammad; Habibi, Emran; Modanloo, Mona

    2017-08-01

    Aim Rosa damascene Mill. belongs to the family of Roseaceae and its essential oil is produced in large amounts in Iran. The wide application of rose oil has raised questions about potential adverse health effects. We have investigated cytotoxic activity and genotoxic effects of Rosa oil from Kashan, Iran. Methods The cytotoxic effect and IC50 of the essential oil on the cell lines was studied followed by MTT assay. In this assay mitochondrial oxidoreductase enzymes with reducing the tetrazolium dye MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) reflect the number of viable cells. Genotoxic effect of the oil was evaluated by micronucleus assay by evaluating produced micronuclei due to cytogenetic damage in binucleated lymphocytes. Results The results showed that essential oil significantly had cytotoxic and genotoxic effects at doses over 10µg/mL (pessential oil of Rose showed lower IC50 in cancer cell line (A549) in comparison with the normal cell line (NIH3T3). Conclusion Cytotoxic and genotoxic properties of essential oil of Rose in Kashan, Iran, are safe at a dose of 10µg/mL. Also, a good cytotoxic effect was shown and could be introduced as an anticancer compound. Further studies are needed with regard to anti-cancer effects of Rose essential oil. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

  4. Genotoxicity of styrene oligomers extracted from polystyrene intended for use in contact with food

    Directory of Open Access Journals (Sweden)

    Makoto Nakai

    2014-01-01

    Full Text Available Here, we conducted in vitro genotoxicity tests to evaluate the genotoxicity of styrene oligomers extracted from polystyrene intended for use in contact with food. Styrene oligomers were extracted with acetone and the extract was subjected to the Ames test (OECD test guideline No. 471 and the in vitro chromosomal aberration test (OECD test guideline No. 473 under good laboratory practice conditions. The concentrations of styrene dimers and trimers in the concentrated extract were 540 and 13,431 ppm, respectively. Extraction with acetone provided markedly higher concentrations of styrene oligomers compared with extraction with 50% ethanol aqueous solution, which is the food simulant currently recommended for use in safety assessments of polystyrene by both the United States Food and Drug Administration and the European Food Safety Authority. And these high concentrations of styrene dimers and trimers were utilized for the evaluation of genotoxicity in vitro. Ames tests using five bacterial tester strains were negative both in the presence or absence of metabolic activation. The in vitro chromosomal aberration test using Chinese hamster lung cells (CHL/IU was also negative. Together, these results suggest that the risk of the genotoxicity of styrene oligomers that migrate from polystyrene food packaging into food is very low.

  5. Conventional and whitening toothpastes: cytotoxicity, genotoxicity and effect on the enamel surface.

    Science.gov (United States)

    Camargo, Samira Esteves Afonso; Jóias, Renata Pilli; Santana-Melo, Gabriela Fátima; Ferreira, Lara Tolentino; El Achkar, Vivian Narana Ribeiro; Rode, Sigmar de Mello

    2014-12-01

    To evaluate the cytotoxicity and genotoxicity of whitening and common toothpastes, and the surface roughness of tooth enamel submitted to brushing with both toothpastes. Samples of whitening toothpastes [Colgate Whitening (CW) and Oral-B Whitening (OBW)] and regular (non-whitening) toothpastes (Colgate and Oral-B) were extracted in culture medium. Gingival human fibroblasts (FMM-1) were placed in contact with different dilutions of culture media that had been previously exposed to such materials, and the cytotoxicity was evaluated using the MTT assay. The genotoxicity was assessed by the micronucleus formation assay in Chinese hamster fibroblasts (V79). The cell survival rate and micronuclei number were assessed before and after exposure to the toothpaste extracts. For the surface roughness evaluation, 20 bovine tooth specimens, divided into four groups according to toothpastes, were submitted to 10,000 brushing cycles. The results were analyzed using the Mann-Whitney U and two-way ANOVA tests (P whitening toothpastes showed the highest numbers of micronuclei compared to the untreated control (UC) (P enamel surface (P whitening toothpastes and Oral-B were cytotoxic to the cells. The whitening toothpastes were more genotoxic to cells in vitro than the common toothpastes, and genotoxicity was more pronounced in the OBW toothpaste.

  6. In Vitro and In Vivo Genotoxicity Assessment of Aristolochia manshuriensis Kom.

    Directory of Open Access Journals (Sweden)

    Youn-Hwan Hwang

    2012-01-01

    Full Text Available Arisolochiae species plants containing aristolochic acids I and II (AA I and AA II are well known to cause aristolochic acid nephropathy (AAN. Recently, there are various approaches to use AAs-containing herbs after the removal of their toxic factors. However, there is little information about genotoxicity of Arisolochiae manshuriensis Kom. (AMK per se. To obtain safety information for AMK, its genotoxicity was evaluated in accordance with OECD guideline. To evaluate genotoxicity of AMK, we tested bacterial reverse mutation assay, chromosomal aberration test, and micronucleus test. Here, we also determined the amounts of AA I and II in AMK (2.85 ± 0.08 and 0.50 ± 0.02 mg/g extract, resp.. In bacterial reverse mutation assay, AMK dose-dependently increased revertant colony numbers in TA98, TA100 and TA1537 regardless of metabolic activation. AMK increased the incidence of chromosomal aberration in Chinese hamster ovary-K1 cells, but there was no statistically significant difference. The incidences of micronucleus in bone marrow erythrocyte were significantly increased in mice after oral administration of AMK (5000 mg/kg, comparing with those of vehicle group (P<0.05. The results of three standard tests suggest that the genotoxicity of AMK is directly related to the AAs contents in AMK.

  7. [Genotoxic damage among artisanal and small-scale mining workers exposed to mercury].

    Science.gov (United States)

    Rosales-Rimache, Jaime A; Elizabeth Malca, Nancy; Alarcón, Jhonatan J; Chávez, Manuel; Gonzáles, Marco Antonio

    2013-01-01

    To determine the genotoxic damage among artisanal and small-scale mining workers exposed to mercury. Observational cross-sectional study which evaluated mercury-exposed workers (n=83), whose cells were collected by mouth swab for further staining, microscopic observance, micronuclei count, and other nuclear alterations. 24-hour urine was also collected for the determination of inorganic mercury. 68.7% of participants were male, the mean age being 43 ± 12,4 years (range: 16-76). The average time of occupational exposure to mercury was 12,1 ± 6,7 years, and the contact with mercury was 4,1 ± 3,6 kg per person per day. 93% of participants failed to wear personal protection gear while handling mercury. Results of biological monitoring showed that 17% of participants had concentrations of mercury in urine higher than 2,5 µg/L, this value being the detection limit of the measurement technique used. Results of the genotoxic evaluation evidenced that 15% of people with labor exposure to mercury presented micronuclei in mouth epithelial cells, and other indicators of nuclear alteration such as nucleoplasmic bridges, gemmation and binucleation were found, which are also considered genotoxic events associated to the exposure of physical or chemical risk agents. The finding of micronuclei in mouth epithelial cells reflects genotoxic damage associated to the labor exposure of mercury used in artisanal and small-scale mining activities.

  8. In vivo genotoxicity assessment in rats exposed to Prestige-like oil by inhalation.

    Science.gov (United States)

    Valdiglesias, Vanessa; Kiliç, Gözde; Costa, Carla; Amor-Carro, Óscar; Mariñas-Pardo, Luis; Ramos-Barbón, David; Méndez, Josefina; Pásaro, Eduardo; Laffon, Blanca

    2012-01-01

    One of the largest oil spill disasters in recent times was the accident of the oil tanker Prestige in front of the Galician coast in 2002. Thousands of people participated in the cleanup of the contaminated areas, being exposed to a complex mixture of toxic substances. Acute and prolonged respiratory symptoms and genotoxic effects were reported, although environmental exposure measurements were restricted to current determinations, such that attribution of effects observed to oil exposure is difficult to establish. The aim of this study was to analyze peripheral blood leukocytes (PBL) harvested from a rat model of subchronic exposure to a fuel oil with similar characteristics to that spilled by the Prestige tanker, in order to determine potential genotoxic effects under strictly controlled, in vivo exposure. Wistar Han and Brown Norway rats were exposed to the oil for 3 wk, and micronucleus test (MN) and comet assay, standard and modified with 8-oxoguanine DNA glycosylase (OGG1) enzyme, were employed to assess genotoxicity 72 h and 15 d after the last exposure. In addition, the potential effects of oil exposure on DNA repair capacity were determined by means of mutagen sensitivity assay. Results obtained from this study showed that inhalation oil exposure induced DNA damage in both Brown Norway and Wistar Han rats, especially in those animals evaluated 15 d after exposure. Although alterations in the DNA repair responses were noted, the sensitivity to oil substances varied depending on rat strain. Data support previous positive genotoxicity results reported in humans exposed to Prestige oil during cleanup tasks.

  9. GENOTOXICITY OF BIOREMEDIATED SOILS FROM THE REILLY TARSITE, ST. LOUIS PARK, MINNESOTA

    Science.gov (United States)

    An in vitro approach was used to measure the genotoxicity of creosote-contaminated soil before and after four bioremediation processes. The soil was taken from the Reilly Tar site, a closed Superfund site in Saint Louis Park, Minnesota. The creosote soil was bioremediated in bios...

  10. Assessment of the Genotoxicity of olive mill waste water (OMWW) with the Vicia faba Micronucleus test

    International Nuclear Information System (INIS)

    El Hajjouji, H.; Pinelli, E.; Revel, J. C.; Hafidi, M.

    2009-01-01

    Olive mill waste water (OMW) can cause serious environmental hazards in olive producing countries, especially around the Mediterranean basin. In Morocco, olive mills are noe of the foremost polluters: the volume of OMW produced annually is estimated at 250 000 m 3 during the season of production. the present study concerns the genotoxicity of OMW generated in mills producing olive oil in Morocco. (Author)

  11. Potential genotoxic effects of melted snow from an urban area revealed by the Allium cepa test.

    Science.gov (United States)

    Blagojević, Jelena; Stamenković, Gorana; Vujosević, Mladen

    2009-09-01

    The presence of well-known atmospheric pollutants is regularly screened for in large towns but knowledge about the effects of mixtures of different pollutants and especially their genotoxic potential is largely missing. Since falling snow collects pollutants from the air, melted snow samples could be suitable for evaluating potential genotoxicity. For this purpose the Allium cepa anaphase-telophase test was used to analyse melted snow samples from Belgrade, the capital city of Serbia. Samples of snow were taken at two sites, characterized by differences in pollution intensity, in three successive years. At the more polluted site the analyses showed a very high degree of both toxicity and genotoxicity in the first year of the study corresponding to the effects of the known mutagen used as the positive control. At the other site the situation was much better but not without warning signals. The results showed that standard analyses for the presence of certain contaminants in the air do not give an accurate picture of the possible consequences of urban air pollution because the genotoxic potential remains hidden. The A. cepa test has been demonstrated to be very convenient for evaluation of air pollution through analyses of melted snow samples.

  12. Assessing the genotoxicity of urban air pollutants using two in situ plant bioassays

    International Nuclear Information System (INIS)

    Villarini, M.; Fatigoni, C.; Dominici, L.; Maestri, S.; Ederli, L.; Pasqualini, S.; Monarca, S.; Moretti, M.

    2009-01-01

    Genotoxicity of urban air has been analysed almost exclusively in airborne particulates. We monitored the genotoxic effects of airborne pollutants in the urban air of Perugia (Central Italy). Two plant bioindicators with different genetic endpoints were used: micronuclei in meiotic pollen mother cells using Tradescantia-micronucleus bioassay (Trad-MCN) and DNA damage in nuclei of Nicotiana tabacum leaves using comet assay (Nicotiana-comet). Buds of Tradescantia clone no. 4430 and young N. tabacum cv. Xanthi plants were exposed for 24 h at three sites with different pollution levels. One control site (indoor control) was also used. The two bioassays showed different sensitivities toward urban pollutants: Trad-MCN assay was the most sensitive, but DNA damage in N. tabacum showed a better correlation with the pollutant concentrations. In situ biomonitoring of airborne genotoxins using higher plants combined with chemical analysis is thus recommended for characterizing genotoxicity of urban air. - Plant bioassays used to explore in situ the correlation between air pollution and genotoxicity.

  13. Relationship between genotoxicity and oxidative stress induced by mercury on common carp (Cyprinus carpio) tissues.

    Science.gov (United States)

    García-Medina, Sandra; Galar-Martínez, Marcela; Gómez-Oliván, Leobardo Manuel; Ruiz-Lara, Karina; Islas-Flores, Hariz; Gasca-Pérez, Eloy

    2017-11-01

    Mercury is one of the most toxic metals in aquatic systems since it is able to induce neurobehavioral disorders as well as renal and gastrointestinal tract damage. The common carp Cyprinus carpio is an important species from both an ecological and economic viewpoint as it is consumed in many countries, the top producers being Mexico, China, India and Japan. The present study aimed to evaluate the relation between Hg-induced oxidative stress and genotoxicity in diverse tissues of C. carpio. Specimens were exposed to 0.01mgHg/L (the maximum permissible limit for aquatic life protection), and lipid peroxidation, protein carbonyl content and the activity of antioxidant enzymes were evaluated at 96h. Micronuclei frequency and DNA damage by comet assay were determined at 12, 24, 48, 72 and 96h. Hg induced oxidative stress and genotoxicity on exposed fish, since inhibition of antioxidant enzymes activity and increases in lipid peroxidation, DNA damage and micronuclei frequency occurred. Blood, gill and liver were more susceptible to oxidative stress, while blood were more sensitive to genotoxicity. In conclusion, Hg at concentrations equal to the maximum permissible limit for aquatic life protection induced oxidative stress and genotoxicity on C. carpio, and these two effects prove to be correlated. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Investigation of genotoxic potential of various sizes Fe2O3 nanoparticles with comet assay

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    İbrahim Hakkı Ciğerci

    2015-06-01

    In this study, genotoxic potential of <50 nm and <100 nm Fe2O3 nanoparticles were investigated by using Comet Assay. Allium cepa root meristems were exposed with five doses (0.001, 0.01, 0.1, 1, 10 mM of <50 nm for 4 hour and three doses (2.5, 5 (EC50, 10 mM for <100 nm of Fe2O3 nanoparticle for 24 and 96 h. Methyl methanesulfonate -MMS (10 ppm was used as a positive control. The results were also analyzed statistically by using SPSS by Windows, 18.0. It was determined that different doses of <50 nm Fe2O3 nanoparticle have no genotoxic effect of DNA. Different doses of <100 nm Fe2O3 have no genotoxic but only 10 mM dose have genotoxic effect on DNA. When compared <50 nm with <100 nm of Fe2O3 nanoparticle; <50 nm have more effects than <100 nm of Fe2O3 on DNA damage.

  15. Genotoxicity and cytotoxicity induced by eluates from orthodontic glass ionomer cements in vitro

    Directory of Open Access Journals (Sweden)

    Fernanda Angelieri

    2018-01-01

    Full Text Available The aim of this study was to investigate genotoxicity and cytotoxicity of some orthodontic glass ionomer cements commercially available by means of the single cell gel (comet assay. For this purpose, five commercial orthodontic glass ionomer cements (Vidrion C®, Meron®, Optiband®, Multicure® and Ultra Band Lok® were tested in murine fibroblasts in vitro. For this purpose, eluates from each cement were prepared according manufactures instructions at 0, 2, 4, 8, 18, 32 and 64 days of immersion in artificial saliva at 37 °C. All orthodontic glass ionomer cements failed to induce cytotoxicity to murine fibroblasts for all periods evaluated in this study. However, Vidrion C® was able to induce genotoxicity after 64 days of exposure to eluates. Meron® also demonstrated genotoxicity as depicted by increasing DNA damage on 2nd day. Multicure® demonstrated genotoxicity on 32nd day and Ultra band Lok on 18th, 32nd days of exposure. Taken together, our results demonstrated that orthodontic cements derived from resin-modified glass ionomer composite (Multicure® and compomer (Ultra Band Lok® cause genetic damage in mammalian cells in vitro.

  16. Genotoxicity and antigenotoxicity assessment of shiitake (Lentinula edodes (Berkeley Pegler using the Comet assay

    Directory of Open Access Journals (Sweden)

    CK Miyaji

    2004-01-01

    Full Text Available The mushroom shiitake (Lentinula edodes (Berkeley Pegler is been widely consumed in many countries, including Brazil, because of its pleasant flavor and reports of its therapeutic properties, although there is little available information on the genotoxicity and/or antigenotoxicity of this mushroom. We used the Comet assay and HEp-2 cells to evaluate the in vitro genotoxic and antigenotoxic activity of aqueous extracts of shiitake prepared in three different concentrations (0.5, 1.0 and 1.5 mg/mL and three different temperatures (4, 22 and 60 °C, using methyl methanesulfonate (MMS as a positive control and untreated cells as a negative control. Two concentrations (1.0 and 1.5 mg/mL of extract prepared at 4 °C and all of the concentrations prepared at 22 ± 2 and 60 °C showed moderate genotoxic activity. To test the protective effect of the three concentrations of the extracts against the genotoxicity induced by methyl methanesulfonate, three protocols were used: pre-treatment, simultaneous-treatment and post-treatment. Treatments were repeated for all combinations of preparation temperature and concentration. Two extracts (22 ± 2 °C 1.0 mg/mL (simultaneous-treatment and 4 °C 0.5 mg/mL (post-treatment showed antigenotoxic activity.

  17. Biodetection of potential genotoxic pollutants entering the human food chain through ashes used in livestock diets.

    Science.gov (United States)

    Sanchez-Vicente, Laura; Herraez, Elisa; Briz, Oscar; Nogales, Rogelio; Molina-Alcaide, Eduarda; Marin, Jose J G

    2016-08-15

    Ash derived from energy generation is used as a source of minerals in livestock feeds. The microbial biosensor recApr-Luc2 was built to detect genotoxic hazard in recycled ash. Escherichia coli SOS gene (recA, lexA, dinI and umuC) expression in response to cisplatin-induced DNA damage led to the selection of the recA promoter. The biosensor required functional RecA expression to respond to genotoxic heavy metals (Cr>Cd≈Pb), and polluted ash induced a strong recApr-Luc2 response. In human liver and intestinal cells, heavy metals induced acute toxicity (Cr>Cd>Pb) at concentrations sufficient to activate recApr-Luc2. Cytostatic effects, including genotoxicity, were cell- and metal-dependent, apart from Cr. In agreement with the recApr-Luc2 bioassay, Cr had the strongest effect in all cells. In conclusion, recApr-Luc2 could be useful for evaluating the genotoxic risk of pollutants present in ash that might be concentrated in animal products and, thus, entering the human food chain. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. High Dose Ascorbate Causes Both Genotoxic and Metabolic Stress in Glioma Cells

    Science.gov (United States)

    Castro, Maria Leticia; Carson, Georgia M.; McConnell, Melanie J.; Herst, Patries M.

    2017-01-01

    We have previously shown that exposure to high dose ascorbate causes double stranded breaks (DSBs) and a build-up in S-phase in glioblastoma (GBM) cell lines. Here we investigated whether or not this was due to genotoxic stress as well as metabolic stress generated by exposure to high dose ascorbate, radiation, ascorbate plus radiation and H2O2 in established and primary GBM cell lines. Genotoxic stress was measured as phosphorylation of the variant histone protein, H2AX, 8-oxo-7,8-dihydroguanine (8OH-dG) positive cells and cells with comet tails. Metabolic stress was measured as a decrease in NADH flux, mitochondrial membrane potential (by CMXRos), ATP levels (by ATP luminescence) and mitochondrial superoxide production (by mitoSOX). High dose ascorbate, ascorbate plus radiation, and H2O2 treatments induced both genotoxic and metabolic stress. Exposure to high dose ascorbate blocked DNA synthesis in both DNA damaged and undamaged cell of ascorbate sensitive GBM cell lines. H2O2 treatment blocked DNA synthesis in all cell lines with and without DNA damage. DNA synthesis arrest in cells with damaged DNA is likely due to both genotoxic and metabolic stress. However, arrest in DNA synthesis in cells with undamaged DNA is likely due to oxidative damage to components of the mitochondrial energy metabolism pathway. PMID:28737676

  19. A MASS BALANCE OF SURFACE WATER GENOTOXICITY IN PROVIDENCE RIVER (RHODE ISLAND USA)

    Science.gov (United States)

    White and Rasmussen (Mutation Res. 410:223-236) used a mass balance approach to demonstrate that over 85% of the total genotoxic loading to the St. Lawrence River at Montreal is non-industrial. To validate the mass balance approach and investigate the sources of genotoxins in sur...

  20. An official American Thoracic Society/International Society for Heart and Lung Transplantation/Society of Critical Care Medicine/Association of Organ and Procurement Organizations/United Network of Organ Sharing Statement: ethical and policy considerations in organ donation after circulatory determination of death.

    Science.gov (United States)

    Gries, Cynthia J; White, Douglas B; Truog, Robert D; Dubois, James; Cosio, Carmen C; Dhanani, Sonny; Chan, Kevin M; Corris, Paul; Dark, John; Fulda, Gerald; Glazier, Alexandra K; Higgins, Robert; Love, Robert; Mason, David P; Nakagawa, Thomas A; Shapiro, Ron; Shemie, Sam; Tracy, Mary Fran; Travaline, John M; Valapour, Maryam; West, Lori; Zaas, David; Halpern, Scott D

    2013-07-01

    Donation after circulatory determination of death (DCDD) has the potential to increase the number of organs available for transplantation. Because consent and management of potential donors must occur before death, DCDD raises unique ethical and policy issues. To develop an ethics and health policy statement on adult and pediatric DCDD relevant to critical care and transplantation stakeholders. A multidisciplinary panel of stakeholders was convened to develop an ethics and health policy statement. The panel consisted of representatives from the American Thoracic Society, Society of Critical Care Medicine, International Society for Heart and Lung Transplantation, Association of Organ Procurement Organizations, and the United Network of Organ Sharing. The panel reviewed the literature, discussed important ethics and health policy considerations, and developed a guiding framework for decision making by stakeholders. A framework to guide ethics and health policy statement was established, which addressed the consent process, pre- and post mortem interventions, the determination of death, provisions of end-of-life care, and pediatric DCDD. The information presented in this Statement is based on the current evidence, experience, and clinical rationale. New clinical research and the development and dissemination of new technologies will eventually necessitate an update of this Statement.

  1. How Critical Is Critical Thinking?

    Science.gov (United States)

    Shaw, Ryan D.

    2014-01-01

    Recent educational discourse is full of references to the value of critical thinking as a 21st-century skill. In music education, critical thinking has been discussed in relation to problem solving and music listening, and some researchers suggest that training in critical thinking can improve students' responses to music. But what exactly is…

  2. The history, genotoxicity, and carcinogenicity of carbon-based fuels and their emissions. Part 3: diesel and gasoline.

    Science.gov (United States)

    Claxton, Larry D

    2015-01-01

    Within this review the genotoxicity of diesel and gasoline fuels and emissions is placed in an historical context. New technologies have changed the composition of transportation methods considerably, reducing emissions of many of the components of health concern. The similarity of modern diesel and gasoline fuels and emissions to other carbonaceous fuels and emissions is striking. Recently an International Agency for Research on Cancer (IARC) Working Group concluded that there was sufficient evidence in humans for the carcinogenicity of diesel exhaust (Group 1). In addition, the Working Group found that diesel exhaust has "a positive association (limited evidence) with an increased risk of bladder cancer." Like most other carbonaceous fuel emissions, diesel and gasoline exhausts contain toxic levels of respirable particles (PM gasoline emissions has declined in certain regions over time because of changes in engine design, the development of better aftertreatment devices (e.g., catalysts), increased fuel economy, changes in the fuels and additives used, and greater regulation. Additional research and better exposure assessments are needed so that decision makers and the public can decide to what extent diesel and gasoline engines should be replaced. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. A Simple and Direct LC-MS Method for Determination of Genotoxic Impurity Hydroxylamine in Pharmaceutical compounds.

    Science.gov (United States)

    Kumar, Thangarathinam; Ramya, Mohandass; Srinivasan, Viswanathan; Xavier, N

    2017-08-01

    Hydroxylamine is a known genotoxic impurity compound that needs to be controlled down to ppm level in pharmaceutical processes. It is difficult to detect using conventional analytical techniques due to its physio-chemical properties like lack of chromophore, low molecular weight, absence of carbon atom and high polarity. In addition to that, analysis of the pharmaceutical samples encounters considerable obstruction from matrix components that greatly overshadow the response of hydroxylamine. This study describes a simple, sensitive and direct Liquid Chromatographic-Mass Spectrometric method (LC-MS) for detection of hydroxylamine in pharmaceutical compounds. The LC-MS method was detected up to 0.008 ppm of hydroxylamine with S/N > 3.0 and quantified up to 0.025 ppm of hydroxylamine with S/N ratio >10.0. This validated method can be applied as a generic method to detect the hydroxylamine for pharmaceutical process control and drug substance release. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Protective Effect of Curcumin against Ionizing Radiation (IR)-induced Cytotoxicity and Genotoxicity in HepG2 Cells

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Dong Min; Nasir Uddin, S. M.; Ryu, Tae Ho; Kang, Mi Young; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-10-15

    Ionizing radiation (IR) has many practical applications such as medicine, foods, agricultures, industries, and research laboratories. However, the increasing use of radiation is associated with radiation accidents threatening human health. It is well known that exposure to IR gives rise to genomic alterations, mutagenesis, and cell death. IR is absorbed directly by DNA, leading to various DNA damages (single or double-strand breaks, base damage, and DNA-DNA or DNA-protein cross-linkages) in many living organisms. Therefore, the development of effective and nontoxic radioprotective agents is of considerable interest. Curcumin (C{sub 12}H{sub 20}O{sub 6}, structure is the major yellow component of Curcuma longa with biological activities (antioxidant, anti-proliferative and anti-inflammatory properties). It has been widely used as food and medicine for a long time. The aim of our present study is to investigate the protective effects of curcumin against IR-induced cytotoxicity and genotoxicity in cultured HepG2 cells.

  5. Electrochemical Genotoxicity Assay Based on a SOS/umu Test Using Hydrodynamic Voltammetry in a Droplet

    Science.gov (United States)

    Kuramitz, Hideki; Sazawa, Kazuto; Nanayama, Yasuaki; Hata, Noriko; Taguchi, Shigeru; Sugawara, Kazuharu; Fukushima, Masami

    2012-01-01

    The SOS/umu genotoxicity assay evaluates the primary DNA damage caused by chemicals from the β-galactosidase activity of S. typhimurium. One of the weaknesses of the common umu test system based on spectrophotometric detection is that it is unable to measure samples containing a high concentration of colored dissolved organic matters, sediment, and suspended solids. However, umu tests with electrochemical detection techniques prove to be a better strategy because it causes less interference, enables the analysis of turbid samples and allows detection even in small volumes without loss of sensitivity. Based on this understanding, we aim to develop a new umu test system with hydrodynamic chronoamperometry using a rotating disk electrode (RDE) in a microliter droplet. PAPG when used as a substrate is not electroactive at the potential at which PAP is oxidized to p-quinone imine (PQI), so the current response of chronoamperometry resulting from the oxidation of PAP to PQI is directly proportional to the enzymatic activity of S. typhimurium. This was achieved by performing genotoxicity tests for 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide (AF-2) and 2-aminoanthracene (2-AA) as model genotoxic compounds. The results obtained in this study indicated that the signal detection in the genotoxicity assay based on hydrodynamic voltammetry was less influenced by the presence of colored components and sediment particles in the samples when compared to the usual colorimetric signal detection. The influence caused by the presence of humic acids (HAs) and artificial sediment on the genotoxic property of selected model compounds such as 4-nitroquinoline-N-oxide (4-NQO), 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), 1,8-dinitropyrene (1,8-DNP) and 1-nitropyrene (1-NP) were also investigated. The results showed that the genotoxicity of 1-NP and MX changed in the presence of 10 mg·L−1 HAs. The genotoxicity of tested chemicals with a high hydrophobicity such as 1,8-DNP

  6. In vivo genotoxicity of nitramines, transformation products of amine-based carbon capture technology

    Directory of Open Access Journals (Sweden)

    Claire Coutris

    2015-05-01

    Full Text Available In times where we need to reduce our CO2 emissions to the atmosphere, it is important to get a clearer picture of the environmental impacts associated with potential mitigation technologies. Chemical absorption with amines is emerging as the most advanced mitigation technology for post-combustion capture of CO2 from fossil fuel power stations. Although the amine solvent used in this technology is recycled during the capture process, degradation products are formed and released into the environment. Among these degradation products, the aliphatic nitramine compounds dimethylnitramine and ethanolnitramine have been identified, whose environmental impact was unknown. In addition to conducting survival, growth and reproduction tests in a range of marine species, we looked into the in vivo genotoxic potential of these two compounds to experimentally exposed fish (Coutris et al. 2015. DNA damage was analyzed in blood samples collected from the caudal vein of juvenile turbot Scophthalmus maximus after 28 day exposure to nitramines, using the 12 mini-gels version of the comet assay, with and without digestion with formamidopyrimidine DNA glycosylase. Although whole organism bioassays indicated that nitramine toxicity through necrosis was low, the genotoxicity assessment revealed contrasting results, with ethanolnitramine found to be more genotoxic than dimethylnitramine by three orders of magnitude. At the lowest ethanolnitramine concentration (1 mg/L, 84 % DNA damage was observed, whereas 100 mg/L dimethylnitramine was required to cause 37 % DNA damage. The mechanisms of genotoxicity were also shown to differ between the two compounds, with oxidation of the DNA bases responsible for over 90 % of the genotoxicity of dimethylnitramine, whereas DNA strand breaks and alkali-labile sites were responsible for over 90 % of the genotoxicity of ethanolnitramine. Fish exposed to > 3 mg/L ethanolnitramine had virtually no DNA left in their red blood cells. The

  7. Lyme Disease: Emergency Department Considerations.

    Science.gov (United States)

    Applegren, Nathan D; Kraus, Chadd K

    2017-06-01

    Lyme disease (LD) is the most common vector-borne illness in North America. Reported cases of LD have increased from approximately 10,000 cases annually in 1991 to >25,000 cases in 2014. Greater recognition, enhanced surveillance, and public education have contributed to the increased prevalence, as have geographic expansion and the number of infected ticks. Cases are reported primarily in the Northeastern United States, Wisconsin, and Minnesota, with children having the highest incidence of LD among all age groups. The increased incidence and prevalence of LD in the United States makes it increasingly more common for patients to present to the emergency department (ED) for tick bites and LD-related chief complaints, such as the characteristic erythema migrans skin manifestation. We sought to review the etiology of LD, describe its clinical presentations and sequela, and provide a practical classification and approach to ED management of patients with LD-related presentations. In this review, ED considerations for LD are presented and clinical presentations and management of the disease at different stages is discussed. Delayed sequelae that have significant morbidity, including Lyme carditis and Lyme neuroborreliosis, are discussed. Diagnostic tests and management are described in detail. The increasing prevalence and growing geographic reach of Lyme disease makes it critically important for emergency physicians to consider the diagnosis in patients presenting with symptoms suggestive of LD and to initiate appropriate treatment to minimize the potential of delayed sequelae. Special consideration should be made for the epidemiology of LD and a high clinical suspicion should be present for patients in endemic areas or with known exposures to ticks. Emergency physicians can play a critical role in the recognition, diagnosis, and treatment of LD. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Genotoxic effects in wild rodents (Rattus rattus and Mus musculus) in an open coal mining area.

    Science.gov (United States)

    León, Grethel; Pérez, Lyda Espitia; Linares, Juan Carlos; Hartmann, Andreas; Quintana, Milton

    2007-06-15

    Coal is a mixture of a variety of compounds containing mutagenic and carcinogenic polycyclic aromatic hydrocarbons. Exposure to coal is considered as an important non-cellular and cellular source of reactive oxygen species that can induce DNA damage. In addition, spontaneous combustion can occur in coal mining areas, further releasing compounds with detrimental effects on the environment. In this study the comet assay was used to investigate potential genotoxic effects of coal mining activities in peripheral blood cells of the wild rodents Rattus rattus and Mus musculus. The study was conducted in a coal mining area of the Municipio de Puerto Libertador, South West of the Departamento de Cordoba, Colombia. Animals from two areas in the coal mining zone and a control area located in the Municipio de Lorica were investigated. The results showed evidence that exposure to coal results in elevated primary DNA lesions in blood cells of rodents. Three different parameters for DNA damage were assessed, namely, DNA damage index, migration length and percentage damaged cells. All parameters showed statistically significantly higher values in mice and rats from the coal mining area in comparison to the animals from the control area. The parameter "DNA Damage Index" was found to be most sensitive and to best indicate a genotoxic hazard. Both species investigated were shown to be sensitive indicators of environmental genotoxicity caused by coal mining activities. In summary, our study constitutes the first investigation of potential genotoxic effects of open coal mining carried out in Puerto Libertador. The investigations provide a guide for measures to evaluate genotoxic hazards, thereby contributing to the development of appropriate measures and regulations for more careful operations during coal mining.

  9. Genotoxicity studies on DNA-interactive telomerase inhibitors with application as anti-cancer agents.

    Science.gov (United States)

    Harrington, Dean J; Cemeli, Eduardo; Carder, Joanna; Fearnley, Jamie; Estdale, Sian; Perry, Philip J; Jenkins, Terence C; Anderson, Diana

    2003-01-01

    Telomerase-targeted strategies have aroused recent interest in anti-cancer chemotherapy, because DNA-binding drugs can interact with high-order tetraplex rather than double-stranded (duplex) DNA targets in tumour cells. However, the protracted cell-drug exposure times necessary for clinical application require that telomerase inhibitory efficacy must be accompanied by both low inherent cytotoxicity and the absence of mutagenicity/genotoxicity. For the first time, the genotoxicity of a number of structurally diverse DNA-interactive telomerase inhibitors is examined in the Ames test using six Salmonella typhimurium bacterial strains (TA1535, TA1537, TA1538, TA98, TA100, and TA102). DNA damage induced by each agent was also assessed using the Comet assay with human lymphocytes. The two assay procedures revealed markedly different genotoxicity profiles that are likely to reflect differences in metabolism and/or DNA repair between bacterial and mammalian cells. The mutational spectrum for a biologically active fluorenone derivative, shown to be mutagenic in the TA100 strain, was characterised using a novel and rapid assay method based upon PCR amplification of a fragment of the hisG46 allele, followed by RFLP analysis. Preliminary analysis indicates that the majority (84%) of mutations induced by this compound are C --> A transversions at position 2 of the missense proline codon of the hisG46 allele. However, despite its genotoxic bacterial profile, this fluorenone agent gave a negative response in the Comet assay, and demonstrates how unwanted systemic effects (e.g., cytotoxicity and genotoxicity) can be prevented or ameliorated through suitable molecular fine-tuning of a candidate drug in targeted human tumour cells. Copyright 2003 Wiley-Liss, Inc.

  10. Ground and surface water for drinking: a laboratory study on genotoxicity using plant tests

    Directory of Open Access Journals (Sweden)

    Donatella Feretti

    2012-02-01

    Full Text Available Surface waters are increasingly utilized for drinking water because groundwater sources are often polluted. Several monitoring studies have detected the presence of mutagenicity in drinking water, especially from surface sources due to the reaction of natural organic matter with disinfectant. The study aimed to investigate the genotoxic potential of the products of reaction between humic substances, which are naturally present in surface water, and three disinfectants: chlorine dioxide, sodium hypochlorite and peracetic acid. Commercial humic acids dissolved in distilled water at different total organic carbon (TOC concentrations were studied in order to simulate natural conditions of both ground water (TOC=2.5 mg/L and surface water (TOC=7.5 mg/L. These solutions were treated with the biocides at a 1:1 molar ratio of C:disinfectant and tested for genotoxicity using the anaphase chromosomal aberration and micronucleus tests in Allium cepa, and the Vicia faba and Tradescantia micronucleus tests. The tests were carried out after different times and with different modes of exposure, and at 1:1 and 1:10 dilutions of disinfected and undisinfected humic acid solutions. A genotoxic effect was found for sodium hypochlorite in all plant tests, at both TOCs considered, while chlorine dioxide gave positive results only with the A.cepa tests. Some positive effects were also detected for PAA (A.cepa and Tradescantia. No relevant differences were found in samples with different TOC values. The significant increase in all genotoxicity end-points induced by all tested disinfectants indicates that a genotoxic potential is exerted even in the presence of organic substances at similar concentrations to those frequently present in drinking water.

  11. Aspect ratio has no effect on genotoxicity of multi-wall carbon nanotubes.

    Science.gov (United States)

    Kim, Jin Sik; Lee, Kyu; Lee, Young Hee; Cho, Hyun Sun; Kim, Ki Heon; Choi, Kyung Hee; Lee, Sang Hee; Song, Kyung Seuk; Kang, Chang Soo; Yu, Il Je

    2011-07-01

    Carbon nanotubes (CNTs) have specific physico-chemical and electrical properties that are useful for telecommunications, medicine, materials, manufacturing processes and the environmental and energy sectors. Yet, despite their many advantages, it is also important to determine whether CNTs may represent a hazard to the environment and human health. Like asbestos, the aspect ratio (length:diameter) and metal components of CNTs are known to have an effect on the toxicity of carbon nanotubes. Thus, to evaluate the toxic potential of CNTs in relation to their aspect ratio and metal contamination, in vivo and in vitro genotoxicity tests were conducted using high-aspect-ratio (diameter: 10-15 nm, length: ~10 μm) and low-aspect-ratio multi-wall carbon nanotubes (MWCNTs, diameter: 10-15 nm, length: ~150 nm) according to OECD test guidelines 471 (bacterial reverse mutation test), 473 (in vitro chromosome aberration test), and 474 (in vivo micronuclei test) with a good laboratory practice system. To determine the treatment concentration for all the tests, a solubility and dispersive test was performed, and a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) solution found to be more suitable than distilled water. Neither the high- nor the low-aspect-ratio MWCNTs induced any genotoxicity in a bacterial reverse mutation test (~1,000 μg/plate), in vitro chromosome aberration test (without S9: ~6.25 μg/ml, with S9: ~50 μg/ml), or in vivo micronuclei test (~50 mg/kg). However, the high-aspect-ratio MWCNTs were found to be more toxic than the low-aspect-ratio MWCNTs. Thus, while high-aspect-ratio MWCNTs do not induce direct genotoxicity or metabolic activation-mediated genotoxicity, genotoxicity could still be induced indirectly through oxidative stress or inflammation.

  12. Genotoxicity assessment of magnetic iron oxide nanoparticles with different particle sizes and surface coatings

    International Nuclear Information System (INIS)

    Liu, Yanping; Xia, Qiyue; Liu, Ying; Zhang, Shuyang; Cheng, Feng; Wang, Li; Li, Hongxia; Xiao, Kai; Zhong, Zhihui

    2014-01-01

    Magnetic iron oxide nanoparticles (IONPs) have been widely used for various biomedical applications such as magnetic resonance imaging and drug delivery. However, their potential toxic effects, including genotoxicity, need to be thoroughly understood. In the present study, the genotoxicity of IONPs with different particle sizes (10, 30 nm) and surface coatings (PEG, PEI) were assessed using three standard genotoxicity assays, the Salmonella typhimurium reverse mutation assay (Ames test), the in vitro mammalian chromosome aberration test, and the in vivo micronucleus assay. In the Ames test, SMG-10 (PEG coating, 10 nm) showed a positive mutagenic response in all the five test bacterial strains with and without metabolic activation, whereas SEI-10 (PEI coating, 10 nm) showed no mutagenesis in all tester strains regardless of metabolic activation. SMG-30 (PEG coating, 30 nm) was not mutagenic in the absence of metabolic activation, and became mutagenic in the presence of metabolic activation. In the chromosomal aberration test, no increase in the incidence of chromosomal aberrations was observed for all three IONPs. In the in vivo micronucleus test, there was no evidence of increased micronuclei frequencies for all three IONPs, indicating that they were not clastogenic in vivo. Taken together, our results demonstrated that IONPs with PEG coating exhibited mutagenic activity without chromosomal and clastogenic abnormalities, and smaller IONPs (SMG-10) had stronger mutagenic potential than larger ones (SMG-30); whereas, IONPs with SEI coating (SEI-10) were not genotoxic in all three standard genotoxicity assays. This suggests that the mutagenicity of IONPs depends on their particle size and surface coating. (paper)

  13. Critical Jostling

    Directory of Open Access Journals (Sweden)

    Pippin Barr

    2016-11-01

    Full Text Available Games can serve a critical function in many different ways, from serious games about real world subjects to self-reflexive commentaries on the nature of games themselves. In this essay we discuss critical possibilities stemming from the area of critical design, and more specifically Carl DiSalvo’s adversarial design and its concept of reconfiguring the remainder. To illustrate such an approach, we present the design and outcomes of two games, Jostle Bastard and Jostle Parent. We show how the games specifically engage with two previous games, Hotline Miami and Octodad: Dadliest Catch, reconfiguring elements of those games to create interactive critical experiences and extensions of the source material. Through the presentation of specific design concerns and decisions, we provide a grounded illustration of a particular critical function of videogames and hope to highlight this form as another valuable approach in the larger area of videogame criticism.

  14. Critical Proximity

    OpenAIRE

    Simon, Jane

    2010-01-01

    This essay considers how written language frames visual objects. Drawing on Michel Foucault’s response to Raymond Roussel’s obsessive description, the essay proposes a model of criticism where description might press up against its objects. This critical closeness is then mapped across the conceptual art practice and art criticism of Ian Burn. Burn attends to the differences between seeing and reading, and considers the conditions which frame how we look at images, including how w...

  15. Criticality Model

    International Nuclear Information System (INIS)

    Alsaed, A.

    2004-01-01

    The ''Disposal Criticality Analysis Methodology Topical Report'' (YMP 2003) presents the methodology for evaluating potential criticality situations in the monitored geologic repository. As stated in the referenced Topical Report, the detailed methodology for performing the disposal criticality analyses will be documented in model reports. Many of the models developed in support of the Topical Report differ from the definition of models as given in the Office of Civilian Radioactive Waste Management procedure AP-SIII.10Q, ''Models'', in that they are procedural, rather than mathematical. These model reports document the detailed methodology necessary to implement the approach presented in the Disposal Criticality Analysis Methodology Topical Report and provide calculations utilizing the methodology. Thus, the governing procedure for this type of report is AP-3.12Q, ''Design Calculations and Analyses''. The ''Criticality Model'' is of this latter type, providing a process evaluating the criticality potential of in-package and external configurations. The purpose of this analysis is to layout the process for calculating the criticality potential for various in-package and external configurations and to calculate lower-bound tolerance limit (LBTL) values and determine range of applicability (ROA) parameters. The LBTL calculations and the ROA determinations are performed using selected benchmark experiments that are applicable to various waste forms and various in-package and external configurations. The waste forms considered in this calculation are pressurized water reactor (PWR), boiling water reactor (BWR), Fast Flux Test Facility (FFTF), Training Research Isotope General Atomic (TRIGA), Enrico Fermi, Shippingport pressurized water reactor, Shippingport light water breeder reactor (LWBR), N-Reactor, Melt and Dilute, and Fort Saint Vrain Reactor spent nuclear fuel (SNF). The scope of this analysis is to document the criticality computational method. The criticality

  16. Hypochondriasis: considerations for ICD-11

    Directory of Open Access Journals (Sweden)

    Odile A. van den Heuvel

    2014-01-01

    Full Text Available The World Health Organization (WHO is currently revisiting the ICD. In the 10th version of the ICD, approved in 1990, hypochondriacal symptoms are described in the context of both the primary condition hypochondriacal disorder and as secondary symptoms within a range of other mental disorders. Expansion of the research base since 1990 makes a critical evaluation and revision of both the definition and classification of hypochondriacal disorder timely. This article addresses the considerations reviewed by members of the WHO ICD-11 Working Group on the Classification of Obsessive-Compulsive and Related Disorders in their proposal for the description and classification of hypochondriasis. The proposed revision emphasizes the phenomenological overlap with both anxiety disorders (e.g., fear, hypervigilance to bodily symptoms, and avoidance and obsessive-compulsive and related disorders (e.g., preoccupation and repetitive behaviors and the distinction from the somatoform disorders (presence of somatic symptom is not a critical characteristic. This revision aims to improve clinical utility by enabling better recognition and treatment of patients with hypochondriasis within the broad range of global health care settings.

  17. Entrepreneurship: Some Considerations

    Directory of Open Access Journals (Sweden)

    V. Martinho

    2016-02-01

    Full Text Available In this work it is presented some considerations about entrepreneurship. Most of these questions are linked with Portuguese context. Portugal has some particularities, namely because the asymmetries between the littoral and the interior. This situation carried out some problems that complicate and prevent the appearance of new innovated business. In a situation of crisis like that we have today this context can become a really problem to solve some questions.

  18. Critical Review

    DEFF Research Database (Denmark)

    Rosenbaum, Ralph K.; Olsen, Stig Irving

    2018-01-01

    Manipulation and mistakes in LCA studies are as old as the tool itself, and so is its critical review. Besides preventing misuse and unsupported claims, critical review may also help identifying mistakes and more justifiable assumptions as well as generally improve the quality of a study. It thus...... supports the robustness of an LCA and increases trust in its results and conclusions. The focus of this chapter is on understanding what a critical review is, how the international standards define it, what its main elements are, and what reviewer qualifications are required. It is not the objective...... of this chapter to learn how to conduct a critical review, neither from a reviewer nor from a practitioner perspective. The foundation of this chapter and the basis for any critical review of LCA studies are the International Standards ISO 14040:2006, ISO 14044:2006 and ISO TS 14071:2014....

  19. Use of the Microscreen phage-induction assay to assess the genotoxicity of 14 hazardous industrial wastes

    Energy Technology Data Exchange (ETDEWEB)

    Houk, V.S.; DeMarini, D.M.

    1988-01-01

    The Microscreen phage-induction assay, which quantitatively measures the induction of prophage lambda in Escherichia coli WP2s lambda, was used to test 14 crude (unfractionated) hazardous industrial-waste samples for genotoxic activity in the presence and absence of metabolic activation. Eleven of the 14 wastes induced prophage, and induction was observed at concentrations as low as 0.4 picograms per ml. Comparisons between the mutagenicity of these waste samples in Salmonella and their ability to induce prophage lambda indicate that the Microscreen phage-induction assay detected genotoxic activity in all but one of the wastes that were mutagenic in Salmonella. Moreover, the Microscreen assay detected as genotoxic 5 additional wastes that were not detected in the Salmonella assay. The applicability of the Microscreen phage-induction assay for screening hazardous wastes for genotoxic activity is discussed along with some of the problems associated with screening highly toxic wastes containing toxic volatile compounds.

  20. Use of the microscreen phage-induction assay to assess the genotoxicity of 14 hazardous industrial wastes

    Energy Technology Data Exchange (ETDEWEB)

    Houk, V.S.; DeMarini, D.M.

    1988-01-01

    The Microscreen phage-induction assay, which quantitatively measures the induction of prophage lambda in Escherichia coli WP2s(lambda), was used to test 14 crude (unfractionated) hazardous industrial waste samples for genotoxic activity in the presence and absence of metabolic activation. Eleven of the 14 wastes induced prophage, and induction was observed at concentrations as low as 0.4 pg per ml. Comparisons between the ability of these waste samples to induce prophage and their mutagenicity in the Salmonella reverse mutation assay indicate that the phage-induction assay detected genotoxic activity in all but one of the wastes that were mutagenic in Salmonella. Moreover, the Microscreen assay detected as genotoxic five additional wastes that were not detected in the Salmonella assay. The applicability of the Microscreen phage-induction assay for screening hazardous wastes for genotoxic activity is discussed, as are some of the problems associated with screening highly toxic wastes containing toxic volatile compounds.

  1. Environmental genotoxicity and risk assessment in the Gulf of Riga (Baltic Sea) using fish, bivalves, and crustaceans.

    Science.gov (United States)

    Butrimavičienė, Laura; Baršienė, Janina; Greiciūnaitė, Janina; Stankevičiūtė, Milda; Valskienė, Roberta

    2018-06-21

    Environmental genotoxicity in the Gulf of Riga was assessed using different bioindicators (fish, clams, and isopods) collected from 14 study stations. Comparison of genotoxicity responses (micronuclei (MN) and nuclear buds (NB)) in blood erythrocytes of herring (Clupea harengus), eelpout (Zoarces viviparous), and flounder (Platichthys flesus) revealed the species- and site-specific differences. For the first time, the analysis of genotoxicity was carried out in gill cells of isopods Saduria entomon. The highest inductions of MN and NB in gill cells of investigated S. entomon and clams (Macoma balthica) were evaluated in specimens from station 111A (offshore zone). In fish, the highest incidences of MN were measured in eelpout and in herring collected in the southern part of Gulf of Riga (station GOR3/41S). Moreover, in the southern coastal area, the assessment of genotoxicity risk (according to micronuclei levels) indicated exceptionally high risk for flounder, eelpout, and clams.

  2. State of the Art High-Throughput Approaches to Genotoxicity: Flow Micronucleus, Ames II, GreenScreen and Comet

    Science.gov (United States)

    State of the Art High-Throughput Approaches to Genotoxicity: Flow Micronucleus, Ames II, GreenScreen and Comet (Presented by Dr. Marilyn J. Aardema, Chief Scientific Advisor, Toxicology, Dr. Leon Stankowski, et. al. (6/28/2012)

  3. Comet assay evaluation of six chemicals of known genotoxic potential in rats.

    Science.gov (United States)

    Hobbs, Cheryl A; Recio, Leslie; Streicker, Michael; Boyle, Molly H; Tanaka, Jin; Shiga, Atsushi; Witt, Kristine L

    2015-07-01

    As a part of an international validation of the in vivo rat alkaline comet assay (comet assay) initiated by the Japanese Center for the Validation of Alternative Methods (JaCVAM) we examined six chemicals for potential to induce DNA damage: 2-acetylaminofluorene (2-AAF), N-nitrosodimethylamine (DMN), o-anisidine, 1,2-dimethylhydrazine dihydrochloride (1,2-DMH), sodium chloride, and sodium arsenite. DNA damage was evaluated in the liver and stomach of 7- to 9-week-old male Sprague Dawley rats. Of the five genotoxic carcinogens tested in our laboratory, DMN and 1,2-DMH were positive in the liver and negative in the stomach, 2-AAF and o-anisidine produced an equivocal result in liver and negative results in stomach, and sodium arsenite was negative in both liver and stomach. 1,2-DMH and DMN induced dose-related increases in hedgehogs in the same tissue (liver) that exhibited increased DNA migration. However, no cytotoxicity was indicated by the neutral diffusion assay (assessment of highly fragmented DNA) or histopathology in response to treatment with any of the tested chemicals. Therefore, the increased DNA damage resulting from exposure to DMN and 1,2-DMH was considered to represent a genotoxic response. Sodium chloride, a non-genotoxic non-carcinogen, was negative in both tissues as would be predicted. Although only two (1,2-DMH and DMN) out of five genotoxic carcinogens produced clearly positive results in the comet assay, the results obtained for o-anisidine and sodium arsenite in liver and stomach cells are consistent with the known mode of genotoxicity and tissue specificity exhibited by these carcinogens. In contrast, given the known genotoxic mode-of-action and target organ carcinogenicity of 2-AAF, it is unclear why this chemical failed to convincingly increase DNA migration in the liver. Thus, the results of the comet assay validation studies conducted in our laboratory were considered appropriate for five out of the six test chemicals. Copyright © 2015

  4. Comparative cytotoxicity and genotoxicity of soluble and particulate hexavalent chromium in human and hawksbill sea turtle (Eretmochelys imbricate) skin cells

    OpenAIRE

    Young, Jamie L.; Wise, Sandra S.; Xie, Hong; Zhu, Cairong; Fukuda, Tomokazu; Wise, John Pierce

    2015-01-01

    Chromium is both a global marine pollutant and a known human health hazard. In this study, we compare the cytotoxicity and genotoxicity of both soluble and particulate chromate in human and hawksbill sea turtle (Eretmochelys imbricata) skin fibroblasts. Our data show that both soluble and particulate Cr(VI) induce concentration-dependent increases in cytotoxicity, genotoxicity, and intracellular Cr ion concentrations in both human and hawksbill sea turtle fibroblasts. Based on administered co...

  5. Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm)

    OpenAIRE

    Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

    2014-01-01

    The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration tes...

  6. Genotoxic Pyrrolizidine Alkaloids — Mechanisms Leading to DNA Adduct Formation and Tumorigenicity

    OpenAIRE

    Ming W. Chou; Ge Lin; Qingsu Xia; Peter P. Fu

    2002-01-01

    Abstract: Plants that contain pyrrolizidine alkaloids are widely distributed in the world. Although pyrrolizidine alkaloids have been shown to be genotoxic and tumorigenic in experimental animals, the mechanisms of actions have not been fully understood. The results of our recent mechanistic studies suggest that pyrrolizidine alkaloids induce tumors via a genotoxic mechanism mediated by 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5Hpyrrolizine (DHP)-derived DNA adduct formation. This mechanism may ...

  7. Furthering critical institutionalism

    Directory of Open Access Journals (Sweden)

    Frances Dalton Cleaver

    2015-03-01

    Full Text Available This special issue furthers the study of natural resource management from a critical institutional perspective. Critical institutionalism (CI is a contemporary body of thought that explores how institutions dynamically mediate relationships between people, natural resources and society. It focuses on the complexity of institutions entwined in everyday social life, their historical formation, the interplay between formal and informal, traditional and modern arrangements, and the power relations that animate them. In such perspectives a social justice lens is often used to scrutinise the outcomes of institutional processes. We argue here that critical institutional approaches have potentially much to offer commons scholarship, particularly through the explanatory power of the concept of bricolage for better understanding institutional change.  Critical institutional approaches, gathering momentum over the past 15 years or so, have excited considerable interest but the insights generated from different disciplinary perspectives remain insufficiently synthesised. Analyses emphasising complexity can be relatively illegible to policy-makers, a fact which lessens their reach. This special issue therefore aims to synthesise critical institutional ideas and so to lay the foundation for moving beyond the emergent stage to make meaningful academic and policy impact. In bringing together papers here we define and synthesise key themes of critical institutionalism, outline the concept of institutional bricolage and identity some key challenges facing this school of thought.

  8. Part 8. Deployment considerations

    International Nuclear Information System (INIS)

    Dance, K.D.; Chang, Y.I.; Daly, T.A.

    1980-01-01

    This report addresses considerations of fast breeder reactor development and deployment from a national perspective. Nations vary greatly in their expertise and interest relative to nuclear power, and hence a single set of steps to be taken by a nation in decision-making on breeder development and deployment cannot be presented. The approach taken in this report is to present discussions on key factors influencing the breeder development and deployment decisions, especially in non-breeder nations, by drawing upon historical perspectives of the Light Water Reactor for comparison

  9. Geophysical considerations of geothermics

    Energy Technology Data Exchange (ETDEWEB)

    Hayakawa, M

    1967-01-01

    The development and utilization of geothermal energy is described from the standpoint of geophysics. The internal temperature of the Earth and the history and composition of magmas are described. Methods of exploration such as gravity, magnetic, thermal and electrical surveys are discussed, as are geochemical and infrared photogrammetric techniques. Examples are provided of how these techniques have been used in Italy and at the Matsukawa geothermal field in Japan. Drilling considerations such as muds, casings and cementing materials are discussed. Solutions are proposed for problems of environmental pollution and plant expansion.

  10. Critical Arts

    African Journals Online (AJOL)

    both formal and informal) in culture and social theory. CRITICAL ARTS aims to challenge and ... Book Review: Brian McNair, An Introduction to Political Communication (3rd edition), London: Routledge, 2003, ISBN 0415307082, 272pp. Phil Joffe ...

  11. Critical Proximity

    Directory of Open Access Journals (Sweden)

    Jane Simon

    2010-09-01

    Full Text Available This essay considers how written language frames visual objects. Drawing on Michel Foucault’s response to Raymond Roussel’s obsessive description, the essay proposes a model of criticism where description might press up against its objects. This critical closeness is then mapped across the conceptual art practice and art criticism of Ian Burn. Burn attends to the differences between seeing and reading, and considers the conditions which frame how we look at images, including how we look at, and through words. The essay goes on to consider Meaghan Morris’s writing on Lynn Silverman’s photographs. Both Morris and Burn offer an alternative to a parasitic model of criticism and enact a patient way of looking across and through visual landscapes.

  12. Critical proximity

    Directory of Open Access Journals (Sweden)

    Simon, Jane

    2010-01-01

    Full Text Available This essay considers how written language frames visual objects. Drawing on Michel Foucault’s response to Raymond Roussel’s obsessive description, the essay proposes a model of criticism where description might press up against its objects. This critical closeness is then mapped across the conceptual art practice and art criticism of Ian Burn. Burn attends to the differences between seeing and reading, and considers the conditions which frame how we look at images, including how we look at, and through words. The essay goes on to consider Meaghan Morris’s writing on Lynn Silverman’s photographs. Both Morris and Burn offer an alternative to a parasitic model of criticism and enact a patient way of looking across and through visual landscapes.

  13. Criticality safety

    International Nuclear Information System (INIS)

    Walker, G.

    1983-01-01

    When a sufficient quantity of fissile material is brought together a self-sustaining neutron chain reaction will be started in it and will continue until some change occurs in the fissile material to stop the chain reaction. The quantity of fissile material required is the 'Critical Mass'. This is not a fixed quantity even for a given type of fissile material but varies between quite wide limits depending on a number of factors. In a nuclear reactor the critical mass of fissile material is assembled under well-defined condition to produce a controllable chain reaction. The same materials have to be handled outside the reactor in all stages of fuel element manufacture, storage, transport and irradiated fuel reprocessing. At any stage it is possible (at least in principle) to assemble a critical mass and thus initiate an accidental and uncontrollable chain reaction. Avoiding this is what criticality safety is all about. A system is just critical when the rate of production of neutrons balances the rate of loss either by escape or by absorption. The factors affecting criticality are, therefore, those which effect neutron production and loss. The principal ones are:- type of nuclide and enrichment (or isotopic composition), moderation, reflection, concentration (density), shape and interaction. Each factor is considered in detail. (author)

  14. Potential genotoxicity of traditional chinese medicinal plants and phytochemicals: an overview.

    Science.gov (United States)

    Zhou, Jue; Ouedraogo, Moustapha; Qu, Fan; Duez, Pierre

    2013-12-01

    In the last decades, cases of poisoning due to herbal medicines have occurred in many countries; Chinese herbal medicines (CHMs) are occasionally involved. The experience gained from traditional use is efficient to detect immediate or near-immediate relationship between administration and toxic effects but is quite unlikely to detect medium- to long-term toxicities; thorough investigations of herbal medicines (toxicity assessments, active pharmacovigilance) appear then essential for their safe use. Genotoxicity is an especially insidious toxicity that may result in carcinoma development years after exposure; it can arise from multiple compounds, with or without metabolic activation. The present work reviews traditional CHMs and phytochemicals that have been shown to present a genotoxic hazard. Copyright © 2013 John Wiley & Sons, Ltd.

  15. Assessment of in vitro genotoxic and cytotoxic effects of flurbiprofen on human cultured lymphocytes.

    Science.gov (United States)

    Timocin, Taygun; Ila, Hasan Basri; Dordu, Tuba; Husunet, Mehmet Tahir; Tazehkand, Mostafa Norizadeh; Valipour, Ebrahim; Topaktas, Mehmet

    2016-01-01

    Flurbiprofen is non-steroidal anti-inflammatory drug which is commonly used for its analgesic, antipyretic, and anti-inflammatory effects. The purpose of the study was to explore the genotoxic and cytotoxic effects of flurbiprofen in human cultured lymphocytes by sister chromatid exchange, chromosome aberration, and cytokinesis-blocked micronucleus tests. 10, 20, 30, and 40 μg/mL concentrations of flurbiprofen (solvent is DMSO) were used to treatment of human cultured lymphocytes at two different treatment periods (24 and 48 h). Flurbiprofen had no significant genotoxic effect in any of these tests. But exposing to flurbiprofen for 24 and 48 h led to significant decrease on proliferation index, mitotic index, and nuclear division index (NDI). Also, all decreases were concentration-dependent (except NDI at 24 h treatment period). Consequently, the findings of this research showed that flurbiprofen had cytotoxic effects in human blood lymphocytes.

  16. Genotoxic Effects of Exposure to Gasoline Fumes on Petrol Pump Workers.

    Science.gov (United States)

    Shaikh, Amrin; Barot, Darshana; Chandel, Divya

    2018-04-01

    Petrol pump workers are occupationally exposed to gasoline and its fumes consisting of several mutagenic chemicals. To evaluate the genotoxic effects of exposure to gasoline fumes on petrol pump workers. The study groups included 70 petrol pump workers (exposed group) and 70 healthy age-matched individuals with no known exposure (comparison group). Buccal micronucleus cytome assay (BMCyt) was performed to check the genotoxicity caused due to inhalation of gasoline fumes. The frequencies of micronucleated cells, nuclear bud, condensed chromatin cells, karyorrhectic cells, pyknotic cells, and karyolytic cells were significantly higher in the exposed workers compared to the comparison group. Exposure to gasoline fumes is associated with increased frequency of cell abnormalities. This may lead to various health consequences including cancer in those occupationally exposed to gasoline fumes.

  17. Genotoxic Effects of Exposure to Gasoline Fumes on Petrol Pump Workers

    Directory of Open Access Journals (Sweden)

    Amrin Shaikh

    2018-04-01

    Full Text Available Background: Petrol pump workers are occupationally exposed to gasoline and its fumes consisting of several mutagenic chemicals. Objective: To evaluate the genotoxic effects of exposure to gasoline fumes on petrol pump workers. Methods: The study groups included 70 petrol pump workers (exposed group and 70 healthy age-matched individuals with no known exposure (comparison group. Buccal micronucleus cytome assay (BMCyt was performed to check the genotoxicity caused due to inhalation of gasoline fumes. Results: The frequencies of micronucleated cells, nuclear bud, condensed chromatin cells, karyorrhectic cells, pyknotic cells, and karyolytic cells were significantly higher in the exposed workers compared to the comparison group. Conclusion: Exposure to gasoline fumes is associated with increased frequency of cell abnormalities. This may lead to various health consequences including cancer in those occupationally exposed to gasoline fumes.

  18. Prophylactic role of some plants and phytochemicals against radio-genotoxicity in human lymphocytes

    Directory of Open Access Journals (Sweden)

    Mohsen Cheki

    2016-01-01

    Full Text Available Genotoxicity in lymphocytes of cancer patients undergoing radiotherapy can lead to lymphocytopenia. Lymphocytopenia induced by radiotherapy is one of the most unfavorable prognostic biological markers in cancer patients, since it has been accepted to be associated with poor prognosis in terms of both survival time and response to cancer therapy. Therefore, reduction in lymphocytopenia may increase treatment efficiency. Research endeavors with synthetic radioprotectors in the past have met with little success primarily due to toxicity-related problems. These disadvantages have led to interest on the use of some plants and phytochemicals as radioprotector. The aim of this paper is to review protective role of some plants and phytochemicals against genotoxicity-induced by ionizing radiation in human blood lymphocytes. Therefore, current review may help the future researches to decrease lymphocytopenia in radiotherapeutic clinical trials.

  19. [Evaluation of cyto- and genotoxic action of ferronanomagnetic and constant magnetic field in in vivo system].

    Science.gov (United States)

    Chekhun, V F; Lozovs'ka, Iu V; Luk'ianova, N Iu; Demash, D V; Todor, I M; Nalieskina, L A

    2013-01-01

    Cyto- and genotoxic effects of nanoparticles on the basis of FM, CMF or their combination have been studied in AKE cells, BM cells of erythroid line, and peripheral blood lymphocytes with the use of MN test and "DNA-comet" assay. It has been shown that expression of mentioned effects is related to FM concentration and duration of tested agent action. It has been also demonstrated that action of CMF alone in the studied cells did not cause any changes in cell architectonics or affect MN counts which are associated with DNA damage. When FM and CMF were used in combination there has been observed the phenomenon of induction of CMF action with FM nanoparticles. The obtained results allow recommend MN test and "DNA-comet" assay as the markers of genome stability in the tests of genotoxic effects of nanomaterials for development of vector nanosystems.

  20. Analyzing the Genotoxicity of Retroviral Vectors in Hematopoietic Cell Gene Therapy

    Directory of Open Access Journals (Sweden)

    Luca Biasco

    2018-03-01

    Full Text Available Retroviral vectors, including those derived from gammaretroviruses and lentiviruses, have found their way into the clinical arena and demonstrated remarkable efficacy for the treatment of immunodeficiencies, leukodystrophies, and globinopathies. Despite these successes, gene therapy unfortunately also has had to face severe adverse events in the form of leukemias and myelodysplastic syndromes, related to the semi-random vector integration into the host cell genome that caused deregulation of neighboring proto-oncogenes. Although improvements in vector design clearly lowered the risk of this insertional mutagenesis, analysis of potential genotoxicity and the consequences of vector integration remain important parameters for basic and translational research and most importantly for the clinic. Here, we review current assays to analyze biodistribution and genotoxicity in the pre-clinical setting and describe tools to monitor vector integration sites in vector-treated patients as a biosafety readout.

  1. Oxidative stress and genotoxicity induced by ketorolac on the common carp Cyprinus carpio.

    Science.gov (United States)

    Galar-Martínez, M; García-Medina, S; Gómez-Olivan, L M; Pérez-Coyotl, I; Mendoza-Monroy, D J; Arrazola-Morgain, R E

    2016-09-01

    The nonsteroidal anti-inflammatory drug ketorolac is extensively used in the treatment of acute postoperative pain. This pharmaceutical has been found at concentrations of 0.2-60 µg/L in diverse water bodies around the world; however, its effects on aquatic organisms remain unknown. The present study, evaluated the oxidative stress and genotoxicity induced by sublethal concentrations of ketorolac (1 and 60 µg/L) on liver, brain, and blood of the common carp Cyprinus carpio. This toxicant induced oxidative damage (increased lipid peroxidation, hydroperoxide content, and protein carbonyl content) as well as changes in antioxidant status (superoxide dismutase, catalase, and glutathione peroxidase activity) in liver and brain of carp. In blood, ketorolac increased the frequency of micronuclei and is therefore genotoxic for the test species. The effects observed were time and concentration dependent. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1035-1043, 2016. © 2015 Wiley Periodicals, Inc.

  2. APPLICATION OF KATG::LUX GENE CONSTRUCT FOR CYTOTOXICITY AND GENOTOXICITY MONITORING OF METOPROLOL IN ENVIRONMENT

    Directory of Open Access Journals (Sweden)

    Eliza Hawrylik

    2017-06-01

    Full Text Available The aim of the study was the evaluation of usefulness of Escherichia coli K-12 RFM 443 katG::lux for cytotoxicity and genotoxicity monitoring of metoprolol in the environment. Metoprolol is one of the most popular cardiac drug which belongs to the group of β – blockers. The drug was applied at concentrations ranging from 10-1 mg/cm3 to 10-5 mg/cm3. Obtained data indicated the influence of metoprolol on lux gene expression and katG promotor activity in E.coli K-12. The results indicato the possibility of using of Escherichia coli K-12 RFM 443 strain with katG::lux gene construct in the monitoring of cytotoxicity and genotoxicity cardiac drug residues in the environment.

  3. Evaluation of toxicity and genotoxicity of 2-chlorophenol on bacteria, fish and human cells.

    Science.gov (United States)

    Vlastos, Dimitris; Antonopoulou, Maria; Konstantinou, Ioannis

    2016-05-01

    Due to the extensive use of chlorophenols (CPs) in anthropogenic activities, 2-Chlorophenol (2-CP), among other CPs, can enter aquatic ecosystems and can be harmful to a variety of organisms, including bacteria, fish and humans, that are exposed directly and/or indirectly to such contaminated environments. Based on the existing knowledge and in order to move a step forward, the purpose of this study is to investigate the toxic and mainly the genotoxic effects of 2-CP using a combination of bioassays. The tests include the marine bacterium Vibrio fischeri and micronuclei induction in the erythrocytes of Carassius auratus as well as in cultured human lymphocytes. The results obtained reveal that 2-CP is able to induce dose-dependent toxic and genotoxic effects on the selected tested concentrations under the specific experimental conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Genotoxicity assessment of cobalt chloride in Eisenia hortensis earthworms coelomocytes by comet assay and micronucleus test.

    Science.gov (United States)

    Ciğerci, İbrahim Hakkı; Ali, Muhammad Muddassir; Kaygısız, Şöhret Yüksek; Liman, Recep

    2016-02-01

    Cobalt and its different compounds are extensively used worldwide and considered as possible environmental pollutant. Earthworms are useful model organism and its different species are used to monitor soil pollution. No study has been found to detect cobalt chloride (CoCl2) genotoxicity in earthworms. So, current study aimed to evaluate CoCl2 induced genotoxicity in Eisenia hortensis earthworms coelomocytes by alkaline comet assay (CA) and micronucleus (MN) test. The earthworms (n = 10 for each group) were exposed to different series of CoCl2 concentrations (100 ppm, 200 ppm, 300 ppm, 400 ppm, 500 ppm, 600 ppm) to find LD50. The LD50 for CoCl2 was found at 226 ppm. Then, doses of LD50/2, LD50 and 2XLD50 for 48 h were used. CA and MN demonstrated the significant increase (P earthworms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. In vivo genotoxic effects of dietary heme iron on rat colon mucosa and ex vivo effects on colon cells monitored by an optimized alkaline comet assay.

    Directory of Open Access Journals (Sweden)

    Océane, C Martin

    2015-04-01

    In conclusion, our results offer a suitable protocol to evaluate genotoxicity on in vivo cryopreserved colon mucosa and on in vitro murine colonic cells, with a middle throughput capacity. This protocol confirms the increase of genotoxicity in rat colon mucosa after an heme-iron diet. Moreover, this protocol enables the demonstration that aldehydes from heme-induced lipoperoxidation are responsible for this increase of genotoxicity.

  6. In vitro and in vivo genotoxicity assessment of HI-6 dimethanesulfonate/oxime.

    Science.gov (United States)

    Nakab, Lauren; Bardot, Isabelle; Bardot, Sébastien; Simar, Sophie; Marzin, Daniel; Nesslany, Fabrice

    2014-03-01

    Organophosphate compounds, which induce organophosphate poisoning, were originally used as pesticides. But this type of product has also been used as warfare nerve agent like sarin, soman, Russian VX, or tabun. HI-6-dimethanesulfonate is a salt of the oxime HI-6 used in the treatment of nerve-agent poisoning. It is known to be the best re-activator component of inactivated acetyl cholinesterase. HI-6-dimethanesulfonate has shown a higher level of solubility with similar potency to reactivate acetyl cholinesterase and a similar pharmacokinetics profile compared with HI-6 dichloride. HI-6 dimethanesulfonate was tested for its mutagenic and genotoxic potential by use of the standard ICH S2R (1) battery for the evaluation of pharmaceuticals. HI-6-dimethanesulfonate was mutagenic in the Ames test only in the presence of metabolic activation. In the mutation assay at the Tk locus in L5178Y mouse-lymphoma cells, HI-6-dimethanesulfonate showed mutagenic activity both with and without metabolic activation, with a significant increase in small colonies. The effects were in favour of a clastogenic activity. It was concluded that the compound was mutagenic and possibly clastogenic in vitro. In contrast, the in vivo micronucleus test in rat bone-marrow did not demonstrate any genotoxic activity and the Comet assay performed in rat liver did not show any statistically or biologically significant increases in DNA strand-breaks. The results of both in vivo studies performed on two different organs with two endpoints are sufficient to conclude the absence of a genotoxic hazard in vivo and to consider that there is no genotoxic concern in humans for HI-6-dimethanesulfonate. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Is Senna Laxative Use Associated to Cathartic Colon, Genotoxicity, or Carcinogenicity?

    OpenAIRE

    Morales, M. A.; Hern?ndez, D.; Bustamante, S.; Bachiller, I.; Rojas, A.

    2009-01-01

    Due to their natural origin, apparent low oral toxicity, effectiveness, and accessibility without a medical prescription, the anthranoid laxatives are a popular remedy for constipation and are frequently used abusively. Therefore, it is important to characterize its harmful and/or toxic effects. The sennosides, main active metabolites of senna, exhibit a very low toxicity in rats, and its genotoxic activity in bacterial strains as well as mammal cells was classified as weak in those cases whe...

  8. Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review

    Science.gov (United States)

    Chappell, Grace; Pogribny, Igor P.; Guyton, Kathryn Z.; Rusyn, Ivan

    2016-01-01

    Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as “carcinogenic to humans” (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments. PMID:27234561

  9. Multi-walled carbon nanotube physicochemical properties predict pulmonary inflammation and genotoxicity

    DEFF Research Database (Denmark)

    Poulsen, Sarah S.; Jackson, Petra; Kling, Kirsten

    2016-01-01

    Lung deposition of multi-walled carbon nanotubes (MWCNT) induces pulmonary toxicity. Commercial MWCNT vary greatly in physicochemical properties and consequently in biological effects. To identify determinants of MWCNT-induced toxicity, we analyzed the effects of pulmonary exposure to 10 commerci...... diameter was associated with increased genotoxicity. This study provides information on possible toxicity-driving physicochemical properties of MWCNT. The results may contribute to safe-by-design manufacturing of MWCNT, thereby minimizing adverse effects....

  10. In vivo assessment of genotoxic, antigenotoxic and anticarcinogenic activities of Solanum lycocarpum fruits glycoalkaloidic extract.

    Directory of Open Access Journals (Sweden)

    Carla Carolina Munari

    Full Text Available The fruits of Solanum lycocarpum, known as wolf-fruit, are used in folk medicine, and because of that we have evaluated both the genotoxic potential of its glycoalkaloidic extract (SL and its influence on the genotoxicity induced by methyl methanesulfonate. Furthermore, the potential blocking effect of SL intake in the initial stage of colon carcinogenesis in Wistar rats was investigated in a short-term (4-week bioassay using aberrant crypt foci (ACF as biomarker. The genotoxic potential was evaluated using the Swiss mice peripheral blood micronucleus test. The animals were treated with different doses of SL (15, 30 and 60 mg/kg b.w. for 14 days, and the peripheral blood samples were collected at 48 h, 7 days and 14 days after starting the treatment. For antigenotoxicity assessment, MMS was administered on the 14th day, and after 24 h the harvesting of bone marrow and liver cells was performed, for the micronucleus and comet assays, respectively. In the ACF assay, male Wistar rats were given four subcutaneous injections of the carcinogen 1,2-dimethylhydrazine (DMH, 40 mg/kg b.w., twice a week, during two weeks to induce ACF. The treatment with SL (15, 30 and 60 mg/kg b.w. was given for four weeks during and after carcinogen treatment to investigate the potential beneficial effects of SL on DMH-induced ACF. The results demonstrated that SL was not genotoxic in the mouse micronucleus test. In animals treated with SL and MMS, the frequencies of micronucleus and extensions of DNA damage were significantly reduced in comparison with the animals receiving only MMS. Regarding the ACF assay, SL significantly reduced the frequency of ACF induced by DMH.

  11. Metabolic profile and genotoxicity in obese rats exposed to cigarette smoke.

    Science.gov (United States)

    Damasceno, Debora C; Sinzato, Yuri K; Bueno, Aline; Dallaqua, Bruna; Lima, Paula H; Calderon, Iracema M P; Rudge, Marilza V C; Campos, Kleber E

    2013-08-01

    Experimental studies have shown that exposure to cigarette smoke has negative effects on lipid metabolism and oxidative stress status. Cigarette smoke exposure in nonpregnant and pregnant rats causes significant genotoxicity (DNA damage). However, no previous studies have directly evaluated the effects of obesity or the association between obesity and cigarette smoke exposure on genotoxicity. Therefore, the aim of the present investigation was to evaluate DNA damage levels, oxidative stress status and lipid profiles in obese Wistar rats exposed to cigarette smoke. Female rats subcutaneously (s.c.) received a monosodium glutamate solution or vehicle (control) during the neonatal period to induce obesity. The rats were randomly distributed into three experimental groups: control, obese exposed to filtered air, and obese exposed to tobacco cigarette smoke. After a 2-month exposure period, the rats were anesthetized and killed to obtain blood samples for genotoxicity, lipid profile, and oxidative stress status analyses. The obese rats exposed to tobacco cigarette smoke presented higher DNA damage, triglycerides, total cholesterol, free fatty acids, VLDL-c, HDL-c, and LDL-c levels compared to control and obese rats exposed to filtered air. Both obese groups showed reduced SOD activity. These results showed that cigarette smoke enhanced the effects of obesity. In conclusion, the association between obesity and cigarette smoke exposure exacerbated the genotoxicity, negatively impacted the biochemical profile and antioxidant defenses and caused early glucose intolerance. Thus, the changes caused by cigarette smoke exposure can trigger the earlier onset of metabolic disorders associated with obesity, such as diabetes and metabolic syndrome. Copyright © 2012 The Obesity Society.

  12. Impact of isomalathion on malathion cytotoxicity and genotoxicity in human HepaRG cells.

    OpenAIRE

    Josse , Rozenn; Sharanek , Ahmad; Savary , Camille C; Guillouzo , André

    2014-01-01

    International audience; Isomalathion is a major impurity of technical grade malathion, one of the most abundantly applied insecticides; however little is known about its hepatotoxicity. In the present study, cytotoxicity and genotoxicity of malathion and isomalathion either individually or in combination, were assessed using the metabolically competent human liver HepaRG cell line. Isomalathion reduced cell viability starting at a 100 μM concentration after a 24h exposure. It also significant...

  13. Protective effect of thymoquinone against diazinon-induced hematotoxicity, genotoxicity and immunotoxicity in rats.

    Science.gov (United States)

    Danaei, Gholam Hassan; Karami, Mohammad

    2017-10-01

    Several studies have shown that oxidative stress and cell damage can occur in the very early stages of diazinon (DZN) exposure. The present study was designed to determine the beneficial effect of thymoquinone (Thy), the main component of Nigella sativa (black seed or black cumin) against DZN immunotoxicity, hematotoxicity and genotoxicity in rats. In the present experimental study, 48 male Wistar rats were randomly divided into six groups, (eight per group) as follows: control (receiving corn oil as the DZN solvent), DZN (20mg/kg), Thy (10mg/kg), Thy (2.5mg/kg)+DZN, Thy (5mg/kg)+DZN and Thy (10mg/kg)+DZN. After four weeks of treatment, the hematological parameters of red blood cells (RBCs), white blood cells (WBCs), hemoglobin (Hb), hematocrit (Hct) and platelets (PLTs) were evaluated. The evaluation of genotoxicity was carried out using the micronucleus assay. For measurement of cytokine production, interferon gamma (IFN-γ), interleukin 10 (IL10) and interleukin 4 (IL4) were chosen as immunotoxicity indicators of DZN toxicity. DZN was found to decrease RBCs, WBCs, Hb, Hct, PLTs, butyrl- and acetyl-cholinesterase activity and I FN-γ and increased the micronucleus indices of IL10 and IL4 as compared with the control group. Treatment with Thy reduced DZN hematotoxicity and immunotoxicity, but, significantly, did not prevent genotoxicity. This study showed that Thy (without the significant effect on genotoxicity) decreased the hematological toxicity, immunotoxicity and butyrl and acetyl cholinesterase activity induced by DZN. The success of Thy supplementation against DZN toxicity can be attributed to the antioxidant effects of its constituents. Copyright © 2017. Published by Elsevier B.V.

  14. Nitrate contamination of drinking water: evaluation of genotoxic risk in human populations.

    OpenAIRE

    Kleinjans, J C; Albering, H J; Marx, A; van Maanen, J M; van Agen, B; ten Hoor, F; Swaen, G M; Mertens, P L

    1991-01-01

    Nitrate contamination of drinking water implies a genotoxic risk to man due to the endogenous formation of carcinogenic N-nitroso compounds from nitrate-derived nitrite. Thus far, epidemiological studies have presented conflicting results on the relation of drinking water nitrate levels with gastric cancer incidence. This uncertainty becomes of relevance in view of the steadily increasing nitrate levels in regular drinking water supplies. In an attempt to apply genetic biomarker analysis to i...

  15. Protective effect of pumpkin seed oil against genotoxicity induced by azathioprine

    OpenAIRE

    Elfiky, S.A.; Elelaimy, I.A.; Hassan, A.M.; Ibrahim, H.M.; Elsayad, R.I.

    2012-01-01

    Pumpkin is a leafy green vegetable; it belongs to the Cucurbitaceae family. Pumpkin seed oil supplementation can prevent changes in plasma lipids and blood pressure. The present study was conducted to evaluate the protective effect of pumpkin seed oil against cytotoxicity and genotoxicity of azathioprine. Oral administration of pumpkin seed oil either before or after treatment of azathioprine was effective in the reduction of the frequencies of Mn-PCEs, decreased the DNA fragmentation, total ...

  16. Tartrazine induces structural and functional aberrations and genotoxic effects in vivo

    OpenAIRE

    Khayyat, Latifa; Essawy, Amina; Sorour, Jehan; Soffar, Ahmed

    2017-01-01

    Tartrazine is a synthetic organic azo dye widely used in food and pharmaceutical products. The current study aimed to evaluate the possible adverse effect of this coloring food additive on renal and hepatic structures and functions. Also, the genotoxic potential of tartrazine on white blood cells was investigated using comet assay. Twenty adult male Wistar rats were grouped into two groups of 10 each, control- and tartrazine-treated groups. The control group was administered orally with water...

  17. Genotoxic evaluation of infusions of Urera baccifera leaves and roots in Allium cepa cells

    Directory of Open Access Journals (Sweden)

    Amanda L. Gindri

    2015-04-01

    Full Text Available Context: The aqueous extracts of Urera baccifera Wedd. leaves and roots are used to inflammatory and infectious diseases in Brazilian folk medicine. Oxalic acid, a substance co-related with toxicity and stinging, was already quantified in this plant. Aims: To evaluate the action of leaves and roots infusions (1, 30, 75 g/L and the oxalic acid standard on mitosis as indicative of presumably antimitotic and genotoxic actions, using the Allium cepa test. Methods: Oxalic acid was quantified in the roots and leaves infusions by High-performance liquid chromatography (HPLC-DAD, with the mobile phase of 25 mM phosphate buffer (pH 2.5: acetonitrile at 95:5 (v/v. To the genotoxicity test, onion bulbs were used. After the rootlets germination, each bulb was submitted for 24 h of the individual treatments. Were analyzed 1000 cells per bulb, in a total of 5000 cells per treatment. Results: Results showed that all concentrations of roots infusions induced chromosomes abnormalities, except for the highest, that caused a substantial inhibition in the mitosis, precluding to be observed abnormalities. In the leaves infusions, only the two higher concentrations caused the highest values of damage in the cellular cycle. The oxalic acid also caused abnormalities in the mitosis, and may be considered responsible by part of the genotoxic action of U. baccifera. Conclusions: Oxalic acid can be responsible by part of the chromosomal abnormalities caused by U. baccifera, although, there must have more metabolites that evoke the same effect promoting the genotoxic effect of this nettle.

  18. EFSA CEF Panel (EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids), 2015. Scientific Opinion on Flavouring Group Evaluation 99 Revision 1 (FGE.99Rev1): Consideration of furanone derivatives evaluated by the JECFA (63rd, 65th and 69th meetings)

    DEFF Research Database (Denmark)

    Beltoft, Vibe Meister; Nørby, Karin Kristiane

    on metabolism and toxicity. The present consideration concerns a group of six furanone derivatives evaluated by the JECFA at their 63rd, 65th and 69th meetings. This revision of FGE.99 includes the assessment of the 2,5-dimethyl-4-methoxyfuran-3(2H)-one [FL-no: 13.089] cleared for genotoxicity concern compared...

  19. EFSA CEF Panel (EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids), 2016. Scientific Opinion on Flavouring Group Evaluation 51, Revision 2 (FGE.51Rev2): Consideration of alicyclic ketones and secondary alcohols and related esters evaluated by the JECFA (59th meeting, ) structurally related to alicyclic ketones secondary alcohols and related esters in FGE.09Rev6 (2015b)

    DEFF Research Database (Denmark)

    Beltoft, Vibe Meister; Nørby, Karin Kristiane

    on metabolism and toxicity. The present consideration concerns a group of 24 alicyclic ketones and secondary alcohols and related esters evaluated by JECFA (59th meeting in 2002 and 63rd meeting in 2004). This revision is made due to inclusion of four additional substances cleared for genotoxicity concern...

  20. Towards Safe Food Free From Pesticides Residues: Biochemical Changes of Selected Vitamins, Trace Elements and Genotoxicity of Irradiated Dates During Storage

    International Nuclear Information System (INIS)

    Farag, S.E.A.; Elsawy, KH.M.; Elgammal, M.H.; Hammoud, G.M.; Youssef, M.S.H.

    2012-01-01

    Decreasing quality of semi-dry dates due to infestation during storage is recorded by many researchers. Low gamma irradiation doses could be considered safe alternative of human toxic chemicals and pesticides. In the present study, semi-dry dates irradiated with different doses of 1, 3, 5 kGy beside non-irradiated samples were stored at 20 degree C and at -18 degree C for nine months. Vitamins E, A and trace elements were determined to check the genotoxicity effect of irradiation at high doses (1, 3, 5, 20 and 30 kGy). Results of high pressure liquid chromatography (HPLC) proved that semi-dry dates contain vitamins A (β-carotene) and E (α-tocopherol) in amounts of 98.78 μg/100 g and 1.818 mg/100 g, respectively, in raw non-irradiated fruits. Degradation of vitamins either naturally during storage or by irradiation was manifested. However, the lowest losses of vitamins were detected at low doses of irradiation (1-3 kGy). Also, trace elements and metals were determined by inductively coupled plasma (ICP) technique. Six trace elements; selenium (Se), zinc (Zn), cupper (Cu), cobalt (Co), chromium (Cr) and nickel (Ni), which are responsible for immunity system were detected in dates with considerable concentrations. Two contaminants heavy metals, lead (Pb) and cadmium (Cd), were detected. All the trace elements were in safe levels and have negligible changes under stress of irradiation and during long storage conditions. The genotoxicity test proved that the increased toxicity of irradiated dates was dose dependant, therefore, the irradiated samples at 1 kGy were safe (near control samples). Consequently, the irradiation at 1 kGy was preferable to be used as an alternative of pesticides in spite of some losses in some bioactive content.

  1. Quantitative comparisons of genotoxic effects of atomic energy and fossil-fuelled energy. Rad-equivalences for ethylene, ethylene oxide and formaldehyde - consequences for decisions at Government level

    International Nuclear Information System (INIS)

    Latarjet, R.; Averbeck, D.; Levy, S.; Poirier, V.

    1982-01-01

    Rad-equivalences have been determined on the basis of data on the genotoxic effects of low linear energy transfer ionizing radiation and of three chemical pollutants - ethylene, ethylene oxide and formaldehyde - emitted from energy-producing power plants. In the case of ethylene and its metabolite, ethylene oxide, the conditions were particularly favourable because the equivalences could be based on the induction of total mutations in the mouse, which is the same genetic end-point used for the assessment of radiation risks. Once established, the rad-equivalences were used (a) to extrapolate the rules adopted for radiation to each of these two compounds and (b) to make recommendations for exposed workers at 'hot spots' and for the general population. Measurements of ethylene in power plants and in the atmosphere of Paris have indicated that in most cases the measured values fall within the recommended values. However, pollution by ethylene oxide in cold sterilization units should be reduced. Rad-equivalences obtained for lethal effects, and for the induction of chromosome aberrations by formaldehyde in human cells in vitro, suggest that the maximum admissible concentrations are far too high in most countries and must be reconsidered. In France, the Ministry of Health is taking the rad-equivalences into consideration for the preparation of a law regulating pollution by ethylene and ethylene oxide - as a first step. These results show that rad-equivalences can be used for risk assessments of genotoxic effects from power plants and that decisions can be made by extrapolating the rules adopted for radiation protection to some chemical mutagens, when certain strict conditions are fulfilled. (author)

  2. Comment on "A re-assessment of the safety of silver in household water treatment: rapid systematic review of mammalian in vivo genotoxicity studies".

    Science.gov (United States)

    Lantagne, Daniele; Rayner, Justine; Mittelman, Anjuliee; Pennell, Kurt

    2017-11-13

    We wish to thank Fewtrell, Majuru, and Hunter for their article highlighting genotoxic risks associated with the use of particulate silver for primary drinking water treatment. The recent promotion of colloidal silver products for household water treatment in developing countries is problematic due to previously identified concerns regarding manufacturing quality and questionable advertising practices, as well as the low efficiency of silver nanoparticles to treat bacteria, viruses, and protozoa in source waters. However, in the conclusion statement of the manuscript, Fewtrell et al. state, "Before colloidal Ag or AgNP are used in filter matrices for drinking water treatment, consideration needs to be given to how much silver is likely to be released from the matrix during the life of the filter." Unfortunately, it appears Fewtrell et al. were unaware that studies of silver nanoparticle and silver ion elution from ceramic filters manufactured and used in developing countries have already been completed. These existing studies have found that: 1) silver ions, not silver nanoparticles, are eluted from ceramic filters treated with silver nanoparticles or silver nitrate; and, 2) silver ions have not been shown to be genotoxic. Thus, the existing recommendation of applying silver nanoparticles to ceramic filters to prevent biofilm formation within the filter and improve microbiological efficacy should still be adhered to, as there is no identified risk to people who drink water from ceramic filters treated with silver nanoparticles or silver nitrate. We note that efforts should continue to minimize exposure to silver nanoparticles (and silica) to employees in ceramic filter factories in collaboration with the organizations that provide technical assistance to ceramic filter factories.

  3. Evaluation of Hypoglycemic and Genotoxic Effect of Polyphenolic Bark Extract from Quercus sideroxyla

    Science.gov (United States)

    Soto-García, Marcela; Rosales-Castro, Martha; Escalona-Cardoso, Gerardo N.

    2016-01-01

    Quercus sideroxyla is a wood species whose bark has phenolic compound and should be considered to be bioactive; the hypoglycemic and genotoxic properties of Q. sideroxyla bark were evaluated in this study. Total phenolic compound was determined in crude extract (CE) and organic extract (OE). The OE has the highest amount of phenols (724.1 ± 12.0 GAE/g). Besides, both CE and OE demonstrated effect over the inhibition of α-amylase in vitro. Hypoglycemic activity was assessed by glucose tolerance curve and the area under curve (UAC); OE showed the highest hypoglycemic activity. In addition, diabetes was induced by streptozotocin (65 mg/kg) and the extracts (50 mg/kg) were administered for 10 days; OE showed hypoglycemic effect compared with diabetic control and decreased hepatic lipid peroxidation. Acute toxicity and genotoxicity were evaluated in CE; results of acute toxicity did not show any mortality. Besides, the comet assay showed that CE at a dose of 100 mg/kg did not show any genotoxic effect when evaluated at 24 h, whereas it induced slight damage at 200 mg/kg, with the formation of type 1 comets. PMID:27867402

  4. Tradescantia micronucleus test indicates genotoxic potential of traffic emissions in European cities

    International Nuclear Information System (INIS)

    Klumpp, Andreas; Ansel, Wolfgang; Klumpp, Gabriele; Calatayud, Vicent; Garrec, Jean Pierre; He Shang; Penuelas, Josep; Ribas, Angela; Ro-Poulsen, Helge; Rasmussen, Stine; Sanz, Maria Jose; Vergne, Phillippe

    2006-01-01

    Urban atmospheres contain complex mixtures of air pollutants including mutagenic and carcinogenic substances such as benzene, diesel soot, heavy metals and polycyclic aromatic hydrocarbons. In the frame of a European network for the assessment of air quality by the use of bioindicator plants, the Tradescantia micronucleus (Trad-MCN) test was applied to examine the genotoxicity of urban air pollution. Cuttings of Tradescantia clone no. 4430 were exposed to ambient air at 65 monitoring sites in 10 conurbations employing a standardised methodology. The tests revealed an elevated genotoxic potential mainly at those urban sites which were exposed to severe car traffic emissions. This bioassay proved to be a suitable tool to detect local 'hot spots' of mutagenic air pollution in urban areas. For its use in routine monitoring programmes, however, further standardisation of cultivation and exposure techniques is recommended in order to reduce the variability of results due to varying environmental conditions. - The Tradescantia micronucleus test can be used to assess genotoxic potential at urban sites

  5. Protective Effects of Quercetin against Dimethoate-Induced Cytotoxicity and Genotoxicity in Allium sativum Test.

    Science.gov (United States)

    Ahmad, Waseem; Shaikh, Sibhghatulla; Nazam, Nazia; Lone, Mohammad Iqbal

    2014-01-01

    The present investigation was directed to study the possible protective activity of quercetin-a natural antioxidant against dimethoate-induced cyto- and genotoxicity in meristematic cells of Allium sativum. So far there is no report on the biological properties of quercetin in plant test systems. Chromosome breaks, multipolar anaphase, stick chromosome, and mitotic activity were undertaken in the current study as markers of cyto- and genotoxicity. Untreated control, quercetin controls (@ 5, 10 and 20 μg/mL for 3 h), and dimethoate exposed groups (@ 100 and 200 μg/mL for 3 h) were maintained. For protection against cytogenotoxicity, the root tip cells treated with dimethoate at 100 and 200 μg/mL for 3 h and quercetin treatment at 5, 10, and 20 μg/mL for 16 h, prior to dimethoate treatment, were undertaken. Quercetin was found to be neither cytotoxic nor genotoxic in Allium sativum control at these doses. A significant increase (P Allium. Pretreatment of Allium sativum with quercetin significantly (P Allium sativum that resides, at least in part, on its antioxidant effects.

  6. Fipronil-induced genotoxicity and DNA damage in vivo: Protective effect of vitamin E.

    Science.gov (United States)

    Badgujar, P C; Selkar, N A; Chandratre, G A; Pawar, N N; Dighe, V D; Bhagat, S T; Telang, A G; Vanage, G R

    2017-05-01

    Fipronil, an insecticide of the phenylpyrazole class has been classified as a carcinogen by United States Environmental Protection Agency, yet very limited information is available about its genotoxic effects. Adult male and female animals were gavaged with various doses of fipronil (2.5, 12.5, and 25 mg/kg body weight (bw)) to evaluate micronucleus test (mice), chromosome aberration (CA), and comet assay (rats), respectively. Cyclophosphamide (40 mg/kg bw; intraperitoneal) was used as positive control. Another group of animals were pretreated with vitamin E orally (400 mg/kg bw) for 5 days prior to administration of fipronil (12.5 mg/kg). Fipronil exposure in both male and female mice caused significant increase in the frequency of micronuclei (MN) in polychromatic erythrocytes. Similarly, structural CAs in bone marrow cells and DNA damage in the lymphocytes was found to be significantly higher in the male and female rats exposed to fipronil as compared to their respective controls. The average degree of protection (male and female animals combined together) shown by pretreatment of vitamin E against fipronil-induced genotoxicity was 63.28%: CAs; 47.91%: MN formation; and 74.70%: DNA damage. Findings of this study demonstrate genotoxic nature of fipronil regardless of gender effect and documents protective role of vitamin E.

  7. Evaluation of genotoxic effect of silver nanoparticles (Ag-Nps) in vitro and in vivo

    International Nuclear Information System (INIS)

    Tavares, Priscila; Balbinot, Fernanda; Martins de Oliveira, Hugo; Elibio Fagundes, Gabriela; Venâncio, Mireli; Vieira Ronconi, João Vitor; Merlini, Aline; Streck, Emílio L.; Marques da Silva, Paula; Moraes de Andrade, Vanessa

    2012-01-01

    Silver nanoparticles (Ag-NPs) are the most prominent nanoproducts. Due to their antimicrobial activity, they have been incorporated in different materials, such as catheters, clothes, electric home appliance, and many others. The genotoxicity of Ag-NPs (5–45 nm), in different concentrations and times of exposure, was evaluated by the comet assay in in vitro and in vivo conditions, respectively, using human peripheral blood and Swiss mice. The results showed the genotoxic effect of Ag-NPs in vitro, in all the doses tested in the initial hour of exposure, possibly through the reactive oxygen species generation. Nevertheless, the values for this damage decrease with time, indicating that the DNA may have been restored by the repair system. In the in vivo conditions, we found no genotoxicity of Ag-NPs in any hour of exposure and any dose investigated, which can be attributed to the activation of a cellular antioxidant network and the hydrophobic nature of Ag-NPs. Now, it is absolutely necessary to investigate the role of Ag-NPs in different cell lines in vivo.

  8. Genotoxic effect of radio marked lymphocytes using Tc-99m complexes

    International Nuclear Information System (INIS)

    Pedraza L, M.; Ferro F, G.; Mendiola C, M.T.; Morales R, P.

    1997-01-01

    The genotoxic effect of radio marked lymphocytes was evaluated using 99m -Tc-HMPAO and 99m -Tc- gentisic acid complexes. With the results of this work it is pretended to contribute to the knowledge of genetic and structural damages that provokes the radiation in the marked lymphocytes. The d, 1-HMPAO was synthesized in laboratory with a yielding of 30 %. The radiochemical purity of the complexes was greater than 85%. Mouse lymphocytes obtained of sanguineous volumes 2 ml were used. The radio marked efficiency of cells was 19.6 ± 6.4% and 25.6 ± 5.8% for 99m Tc-HMPAO and 99m Tc gentisic acid respectively. The genotoxic effect was evaluated using the technique of Unicellular Electrophoresis in Micro gel (Comet assay). The results showed that both 99m Tc complexes produce genotoxicity due to their capacity to penetrate cells, therefore the Auger and M internal conversion electrons place all their energy obtaining doses of Gray order. (Author)

  9. In vitro evaluation of genotoxic effects under magnetic resonant coupling wireless power transfer.

    Science.gov (United States)

    Mizuno, Kohei; Shinohara, Naoki; Miyakoshi, Junji

    2015-04-07

    Wireless power transfer (WPT) technology using the resonant coupling phenomenon has been widely studied, but there are very few studies concerning the possible relationship between WPT exposure and human health. In this study, we investigated whether exposure to magnetic resonant coupling WPT has genotoxic effects on WI38VA13 subcloned 2RA human fibroblast cells. WPT exposure was performed using a helical coil-based exposure system designed to transfer power with 85.4% efficiency at a 12.5-MHz resonant frequency. The magnetic field at the positions of the cell culture dishes is approximately twice the reference level for occupational exposure as stated in the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines. The specific absorption rate at the positions of the cell culture dishes matches the respective reference levels stated in the ICNIRP guidelines. For assessment of genotoxicity, we studied cell growth, cell cycle distribution, DNA strand breaks using the comet assay, micronucleus formation, and hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene mutation, and did not detect any significant effects between the WPT-exposed cells and control cells. Our results suggest that WPT exposure under the conditions of the ICNIRP guidelines does not cause detectable cellular genotoxicity.

  10. Photochemical fate and eco-genotoxicity assessment of the drug etodolac

    Energy Technology Data Exchange (ETDEWEB)

    Passananti, Monica [Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Complesso Universitario Monte S. Angelo, via Cintia, 4, 80126 Napoli (Italy); Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand (ICCF) UMR 6296, BP 10448, F-63000 Clermont-Ferrand (France); Lavorgna, Margherita [Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Via Vivaldi 43, I-81100 Caserta (Italy); Iesce, Maria Rosaria, E-mail: iesce@unina.it [Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Complesso Universitario Monte S. Angelo, via Cintia, 4, 80126 Napoli (Italy); DellaGreca, Marina [Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Complesso Universitario Monte S. Angelo, via Cintia, 4, 80126 Napoli (Italy); Brigante, Marcello [Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand (ICCF) UMR 6296, BP 10448, F-63000 Clermont-Ferrand (France); Criscuolo, Emma [Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Via Vivaldi 43, I-81100 Caserta (Italy); Cermola, Flavio [Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Complesso Universitario Monte S. Angelo, via Cintia, 4, 80126 Napoli (Italy); Isidori, Marina, E-mail: marina.isidori@unina2.it [Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Via Vivaldi 43, I-81100 Caserta (Italy)

    2015-06-15

    The photochemical behavior of etodolac was investigated under various irradiation conditions. Kinetic data were obtained after irradiation of 10{sup −4} M aqueous solutions by UVB, UVA and direct exposure to sunlight. The Xenon lamp irradiation was used in order to determine the photodegradation quantum yield under sun-simulated condition (ϕ{sub sun}). The value was determined to be = 0.10 ± 0.01. In order to obtain photoproducts and for mechanistic purposes, experiments were carried out on more concentrated solutions by exposure to sunlight and to UVA and UVB lamps. The drug underwent photooxidative processes following an initial oxygen addition to the double bond of the five membered ring and was mainly converted into a spiro compound and a macrolactam. Ecotoxicity tests were performed on etodolac, its photostable spiro derivative and its sunlight irradiation mixture on two different aquatic trophic levels, plants (algae) and invertebrates (rotifers and crustaceans). Mutagenesis and genotoxicity were detected on bacterial strains. The results showed that only etodolac had long term effects on rotifers although at concentrations far from environmental detection values. A mutagenic and genotoxic potential was found for its derivative. - Highlights: • Photochemical transformation of etodolac occurs in the environment. • Etodolac was slightly toxic in the long term for some aquatic organisms. • A mutagenic and genotoxic potential was found for etodolac photostable derivative.

  11. Effect of a base-catalyzed dechlorination process on the genotoxicity of PCB-contaminated soil

    Energy Technology Data Exchange (ETDEWEB)

    DeMarini, D.M.; Houk, V.S.; Kornel, A.; Rogers, C.J.

    1992-01-01

    We evaluated the genotoxicity of dichloromethane (DCM) extracts of PCB-contaminated soil before and after the soil had been treated by a base-catalyzed dechlorination process, which involved heating a mixture of the soil, polyethylene glycol, and sodium hydroxide to 250-350 C. This dechlorination process reduced by over 99% the PCB concentration in the soil, which was initially 2,200 ppm. The DCM extracts of both control and treated soils were not mutagenic in strain TA100 of Salmonella, but they were mutagenic in strain TA98. The base-catalyzed dechlorination process reduced the mutagenic potency of the soil by approximately one-half. The DCM extracts of the soils before and after treatment were equally genotoxic in a prophage-induction assay in E. coli, which detects some chlorinated organic carcinogens that were not detected by the Salmonella mutagenicity assay. These results show that treatment of PCB-contaminated soil by this base-catalyzed dechlorination process did not increase the genotoxicity of the soil.

  12. In vitro and in vivo genotoxic effects of somatic cell nuclear transfer cloned cattle meat.

    Science.gov (United States)

    Lee, Nam-Jin; Yang, Byoung-Chul; Jung, Yu-Ri; Lee, Jung-Won; Im, Gi-Sun; Seong, Hwan-Hoo; Park, Jin-Ki; Kang, Jong-Koo; Hwang, Seongsoo

    2011-09-01

    Although the nutritional composition and health status after consumption of the meat and milk derived from both conventionally bred (normal) and somatic cell nuclear transferred (cloned) animals and their progeny are not different, little is known about their food safeties like genetic toxicity. This study is performed to examine both in vitro (bacterial mutation and chromosome aberration) and in vivo (micronucleus) genotoxicity studies of cloned cattle meat. The concentrations of both normal and cloned cattle meat extracts (0-10×) were tested to five strains of bacteria (Salmonella typhimurium: TA98, TA100, TA1535, and TA1537; Escherichia coli: WP2uvrA) for bacterial mutation and to Chinese hamster lung (CHL/IU) cells for chromosome aberration, respectively. For micronucleus test, ICR mice were divided into five dietary groups: commercial pellets (control), pellets containing 5% (N-5) and 10% (N-10) normal cattle meat, and pellets containing 5% (C-5) and 10% (C-10) cloned cattle meat. No test substance-related genotoxicity was noted in the five bacterial strains, CHL/IU cells, or mouse bone marrow cells, suggesting that the cloned cattle meat potentially may be safe in terms of mutagenic hazards. Thus, it can be postulated that the cloned cattle meat do not induce any harmful genotoxic effects in vitro and in vivo. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Evaluation of genotoxicity and cytotoxicity of water samples from the Sinos River Basin, southern Brazil

    Directory of Open Access Journals (Sweden)

    E Bianchi

    Full Text Available Some water bodies in the Sinos River Basin (SRB have been suffering the effects of pollution by residential, industrial and agroindustrial wastewater. The presence of cytotoxic and genotoxic compounds could compromise the water quality and the balance of these ecosystems. In this context, the research aimed to evaluate the genotoxicity and cytotoxicity of the water at four sites along the SRB (in the cities of Santo Antônio da Patrulha, Parobé, Campo Bom and Esteio, using bioassays in fish and cell culture. Samples of surface water were collected and evaluated in vitro using the Astyanax jacuhiensis fish species (micronucleus test and comet assay and the Vero lineage of cells (comet assay and cytotoxicity tests, neutral red - NR and tetrazolium MTT. The micronucleus test in fish showed no significant differences between the sampling sites, and neither did the comet assay and the MTT and NR tests in Vero cells. The comet assay showed an increase in genetic damage in the fish exposed to water samples collected in the middle and lower sections of the basin (Parobé, Campo Bom and Esteio when compared to the upper section of the basin (Santo Antônio da Patrulha. The results indicate contamination by genotoxic substances starting in the middle section of the SRB.

  14. Genotoxic activities of the food contaminant 5-hydroxymethylfurfural using different in vitro bioassays.

    Science.gov (United States)

    Severin, Isabelle; Dumont, Coralie; Jondeau-Cabaton, Adeline; Graillot, Vanessa; Chagnon, Marie-Christine

    2010-02-01

    5-Hydroxymethylfurfural (5-HMF) is known as an indicator of quality deterioration in a wide range of foods. 5-HMF is formed as an intermediate in the Maillard reaction and has been identified in a wide variety of heat-processed foods. In recent years, the presence of 5-HMF in foods has raised toxicological concerns: data have shown cytotoxic, genotoxic and tumoral effects but further studies suggest that 5-HMF does not pose a serious health risk. However the subject is still a matter of debate. We investigated the genotoxicity of the food-borne contaminant 5-HMF using the Ames test, the micronucleus (MN) and the single-cell gel electrophoresis (SCGE) assays in the human metabolically active HepG2 cell line. Cytotoxic effect of 5-HMF was first assessed using Alamar Blue as a sensitive sub-lethal assay. 5-HMF did not induce any genic mutation in bacteria whatever the concentration in the Ames test. Furthermore, it does not induce clastogenic or aneugenic effects in the HepG2 cells. In contrast, 5-HMF induced HepG2 DNA damage at concentrations from 7.87 to 25 mM in the comet assay suggesting a weak genotoxic effect of 5-HMF in the HepG2 cells probably repaired. 2009 Elsevier Ireland Ltd. All rights reserved.

  15. Genotoxic effects of vinclozolin on the aquatic insect Chironomus riparius (Diptera, Chironomidae).

    Science.gov (United States)

    Aquilino, Mónica; Sánchez-Argüello, Paloma; Martínez-Guitarte, José-Luis

    2018-01-01

    Vinclozolin (Vz) is a pollutant found in aquatic environments whose antiandrogenic effects in reproduction are well known in mammals. Although its reproductive effects have been less studied in invertebrates, other effects, including genotoxicity, have been described. Therefore, in this work, we studied the genotoxic effects of Vz in the freshwater benthic invertebrate Chironomus riparius. DNA damage was evaluated with the comet assay (tail area, olive moment, tail moment and % DNA in tail), and the transcriptional levels of different genes involved in DNA repair (ATM, NLK and XRCC1) and apoptosis (DECAY) were measured by RT-PCR. Fourth instar larvae of C. riparius, were exposed to Vz for 24 h at 20 and 200 μg/L. The Vz exposures affected the DNA integrity in this organism, since a dose-response relationship occurred, with DNA strand breaks significantly increased with increased dose for tail area, olive moment and tail moment parameters. Additionally, the lower concentration of Vz produced a significant induction of the transcripts of three genes under study (ATM, NLK and XRCC1) showing the activation of the cellular repair mechanism. In contrast, the expression of these genes with the highest concentration were downregulated, indicating failure of the cellular repair mechanism, which would explain the higher DNA damage. These data report for the first time the alterations of Vz on gene transcription of an insect and confirm the potential genotoxicity of this compound on freshwater invertebrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Genotoxic Effects of Superconducting Static Magnetic Fields (SMFs) on Wheat (Triticum aestivum) Pollen Mother Cells (PMCs)

    International Nuclear Information System (INIS)

    Zhang Pingping; Yin Ruochun; Chen Zhiyou; Wu Lifang; Yu Zengliang

    2007-01-01

    The effects of superconducting static magnetic fields (SMFs) on the pollen mother cells (PMCs) of wheat were investigated in order to evaluate the possible genotoxic effect of such non-ionizing radiation. The seeds of wheat were exposed to static magnetic fields with either different magnetic flux densities (0, 1, 3, 5 and 7 Tesla) for 5 h or different durations (1, 3 and 5 h) at a magnetic flux density of 7 Tesla. The seeds were germinated at 23 o C after exposure and the seedlings were transplanted into the field. The PMCs from young wheat ears were taken and slides were made following the conventional method. The genotoxic effect was evaluated in terms of micronucleus (MN), chromosomal bridge, lagging chromosome and fragments in PMCs. Although the exposed groups of a low field intensity (below 5 Tesla) showed no statistically significant difference in the aberration frequency compared with the unexposed control groups and sham exposed groups, a significant increase in the chromosomal bridge, lagging chromosome, triple-polar segregation or micronucleus was observed at a field strength of 5 Tesla or 7 Tesla, respectively. The analysis of dose-effect relationships indicated that the increased frequency of meiotic abnormal cells correlated with the flux density of the magnetic field and duration, but no linear relationship was observed. Such statistically significant differences indicated a potential genotoxic effect of high static magnetic fields above 5 T

  17. Chemical fate and genotoxic risk associated with hypochlorite treatment of nicotine

    International Nuclear Information System (INIS)

    Zarrelli, Armando; DellaGreca, Marina; Parolisi, Alice; Iesce, Maria Rosaria; Cermola, Flavio; Temussi, Fabio; Isidori, Marina; Lavorgna, Margherita; Passananti, Monica; Previtera, Lucio

    2012-01-01

    Nicotine, the main alkaloid of tobacco, is a non- prescription drug to which all members of a tobacco-smoking society are exposed either through direct smoke inhalation or through second-hand passive ‘smoking’. Nicotine is also commercially available in some pharmaceutical products and is used worldwide as a botanical insecticide in agriculture. Nicotine dynamics in indoor and outdoor environments as well as the human excretions and the manufacturing process are responsible for its entry in the environment through municipal and industrial wastewater discharges. The presence of nicotine in surface and ground waters points out that it survives a conventional treatment process and persists in potable-water supplies. Complete removal of nicotine is instead reported when additional chlorination steps are used. In this paper a simulation of STP chlorination of nicotine and a genotoxic evaluation of its main degradation products are reported. Under laboratory conditions removal of nicotine seems not to be due to mineralization but to transformation in oxidized and chlorinated products. The by-products have been isolated after fractionation by diverse chromatographic procedures and their structures determined using mass spectrometry and 1 H and 13 C NMR spectroscopy. Preliminary genotoxic SOS Chromotests with Escherichia coli PQ37 evidence no toxicity of the products. - Highlights: ► Processes of chlorination in the treatment of raw water. ► STP chlorination of nicotine. ► Genotoxic evaluation of main degradation products of nicotine.

  18. Tradescantia micronucleus test indicates genotoxic potential of traffic emissions in European cities

    Energy Technology Data Exchange (ETDEWEB)

    Klumpp, Andreas [Institute for Landscape and Plant Ecology (320), University of Hohenheim, 70593 Stuttgart (Germany)]. E-mail: aklumpp@uni-hohenheim.de; Ansel, Wolfgang [Institute for Landscape and Plant Ecology (320), University of Hohenheim, 70593 Stuttgart (Germany); Klumpp, Gabriele [Institute for Landscape and Plant Ecology (320), University of Hohenheim, 70593 Stuttgart (Germany); Calatayud, Vicent [Fundacion CEAM, Parque Tecnologico, c/Charles Darwin 14, 46980 Paterna, Valencia (Spain); Garrec, Jean Pierre [INRA Nancy, Laboratoire Pollution Atmospherique, 54280 Champenoux (France); He Shang [INRA Nancy, Laboratoire Pollution Atmospherique, 54280 Champenoux (France); Penuelas, Josep [Unitat Ecofisiologia CSIC-CEAB-CREAF, Universitat Autonoma de Barcelona, Ed. C, 08193 Bellaterra, Barcelona (Spain); Ribas, Angela [Unitat Ecofisiologia CSIC-CEAB-CREAF, Universitat Autonoma de Barcelona, Ed. C, 08193 Bellaterra, Barcelona (Spain); Ro-Poulsen, Helge [Botanical Institute, University of Copenhagen, Oster Farimagsgade 2D, 1353 Copenhagen K (Denmark); Rasmussen, Stine [Botanical Institute, University of Copenhagen, Oster Farimagsgade 2D, 1353 Copenhagen K (Denmark); Sanz, Maria Jose [Fundacion CEAM, Parque Tecnologico, c/Charles Darwin 14, 46980 Paterna, Valencia (Spain); Vergne, Phillippe [ENS Lyon and Lyon Botanical Garden, 46 Allee d' Italie, 69364 Lyon Cedex 07 (France)

    2006-02-15

    Urban atmospheres contain complex mixtures of air pollutants including mutagenic and carcinogenic substances such as benzene, diesel soot, heavy metals and polycyclic aromatic hydrocarbons. In the frame of a European network for the assessment of air quality by the use of bioindicator plants, the Tradescantia micronucleus (Trad-MCN) test was applied to examine the genotoxicity of urban air pollution. Cuttings of Tradescantia clone no. 4430 were exposed to ambient air at 65 monitoring sites in 10 conurbations employing a standardised methodology. The tests revealed an elevated genotoxic potential mainly at those urban sites which were exposed to severe car traffic emissions. This bioassay proved to be a suitable tool to detect local 'hot spots' of mutagenic air pollution in urban areas. For its use in routine monitoring programmes, however, further standardisation of cultivation and exposure techniques is recommended in order to reduce the variability of results due to varying environmental conditions. - The Tradescantia micronucleus test can be used to assess genotoxic potential at urban sites.

  19. Genotoxic effects of N-nitrosodimethylamine in somatic and generative cells of mice

    Directory of Open Access Journals (Sweden)

    Anna V. Lovinskaya

    2017-10-01

    Full Text Available N-Nitrosodimethylamine (NDMA was shown to have genotoxic properties in acute and subacute studies on laboratory mice. The organ-specificity of the genotoxic effect of NDMA was revealed using the Comet assay. The most sensitive organs to the action of NDMA were kidneys and liver. DNA damage in liver cells of NDMA-treated animals at doses of 4.0 and 8.0 mg/kg, increased compared to control in 6.9 and 12.5 (р < 0.001, and in kidney cells – in 8.1 and 14.2 times (р < 0.001, respectively. NDMA also showed genotoxic activity in the reproductive cells of experimental animals, causing structural disorders of synaptonemal complexes in spermatocyte. In NDMA-treated animals at a dose of 2.0 mg/kg in acute and subacute studies, the level of spermatocytes with damaged synaptonemal complexes increased statistically significantly compared to control in 6.0 and 7.0 (р < 0.05 times, respectively.

  20. Embryotoxicity and genotoxicity evaluation of sediments from Yangtze River estuary using zebrafish (Danio rerio) embryos.

    Science.gov (United States)

    Li, Qian; Chen, Ling; Liu, Li; Wu, Lingling

    2016-03-01

    Sediments function both as a sink and a source of pollutants in aquatic ecosystems and may impose serious effects on benthic organisms and human health. As one of the largest estuaries in the world, the Yangtze River estuary suffers from abundant wastewater from the coastal cities. In this study, the zebrafish (Danio rerio) embryos were employed in the fish embryo test and a comet assay to evaluate the embryotoxicity and genotoxicity of the sediments from the Yangtze River estuary, respectively. Results showed that the sediments from the Yangtze River estuary significantly increased mortality, induced development abnormalities, and reduced hatching rate and heart rate of zebrafish embryos after 96 h of exposure. Significant genotoxicity was observed in the samples relative to the controls. Relatively low-level embryotoxicity and genotoxicity of sediments were found in the Yangtze River compared with other river systems. Toxic responses were also discussed in relation to the analyzed organic contaminants in sediments. More attention should be paid to non-priority pollutant monitoring in the Yangtze River estuary.

  1. Carboxylated nanodiamonds are neither cytotoxic nor genotoxic on liver, kidney, intestine and lung human cell lines.

    Science.gov (United States)

    Paget, V; Sergent, J A; Grall, R; Altmeyer-Morel, S; Girard, H A; Petit, T; Gesset, C; Mermoux, M; Bergonzo, P; Arnault, J C; Chevillard, S

    2014-08-01

    Although nanodiamonds (NDs) appear as one of the most promising nanocarbon materials available so far for biomedical applications, their risk for human health remains unknown. Our work was aimed at defining the cytotoxicity and genotoxicity of two sets of commercial carboxylated NDs with diameters below 20 and 100 nm, on six human cell lines chosen as representative of potential target organs: HepG2 and Hep3B (liver), Caki-1 and Hek-293 (kidney), HT29 (intestine) and A549 (lung). Cytotoxicity of NDs was assessed by measuring cell impedance (xCELLigence® system) and cell survival/death by flow cytometry while genotoxicity was assessed by γ-H2Ax foci detection, which is considered the most sensitive technique for studying DNA double-strand breaks. To validate and check the sensitivity of the techniques, aminated polystyrene nanobeads were used as positive control in all assays. Cell incorporation of NDs was also studied by flow cytometry and luminescent N-V center photoluminescence (confirmed by Raman microscopy), to ensure that nanoparticles entered the cells. Overall, we show that NDs effectively entered the cells but NDs do not induce any significant cytotoxic or genotoxic effects on the six cell lines up to an exposure dose of 250 µg/mL. Taken together these results strongly support the huge potential of NDs for human nanomedicine but also their potential as negative control in nanotoxicology studies.

  2. Chemical fate and genotoxic risk associated with hypochlorite treatment of nicotine

    Energy Technology Data Exchange (ETDEWEB)

    Zarrelli, Armando, E-mail: zarrelli@unina.it [UdR Napoli 4 Consorzio INCA, IC-REACH, Department of Organic Chemistry and Biochemistry, University Federico II, Naples (Italy); DellaGreca, Marina; Parolisi, Alice; Iesce, Maria Rosaria; Cermola, Flavio; Temussi, Fabio [UdR Napoli 4 Consorzio INCA, IC-REACH, Department of Organic Chemistry and Biochemistry, University Federico II, Naples (Italy); Isidori, Marina; Lavorgna, Margherita [Department of Life Sciences, II University of Naples, Caserta (Italy); Passananti, Monica; Previtera, Lucio [UdR Napoli 4 Consorzio INCA, IC-REACH, Department of Organic Chemistry and Biochemistry, University Federico II, Naples (Italy)

    2012-06-01

    Nicotine, the main alkaloid of tobacco, is a non- prescription drug to which all members of a tobacco-smoking society are exposed either through direct smoke inhalation or through second-hand passive 'smoking'. Nicotine is also commercially available in some pharmaceutical products and is used worldwide as a botanical insecticide in agriculture. Nicotine dynamics in indoor and outdoor environments as well as the human excretions and the manufacturing process are responsible for its entry in the environment through municipal and industrial wastewater discharges. The presence of nicotine in surface and ground waters points out that it survives a conventional treatment process and persists in potable-water supplies. Complete removal of nicotine is instead reported when additional chlorination steps are used. In this paper a simulation of STP chlorination of nicotine and a genotoxic evaluation of its main degradation products are reported. Under laboratory conditions removal of nicotine seems not to be due to mineralization but to transformation in oxidized and chlorinated products. The by-products have been isolated after fractionation by diverse chromatographic procedures and their structures determined using mass spectrometry and {sup 1}H and {sup 13}C NMR spectroscopy. Preliminary genotoxic SOS Chromotests with Escherichia coli PQ37 evidence no toxicity of the products. - Highlights: Black-Right-Pointing-Pointer Processes of chlorination in the treatment of raw water. Black-Right-Pointing-Pointer STP chlorination of nicotine. Black-Right-Pointing-Pointer Genotoxic evaluation of main degradation products of nicotine.

  3. In vitro cytotoxic, genotoxic and antioxidant/oxidant effects of guaiazulene on human lymphocytes

    Directory of Open Access Journals (Sweden)

    Başak Toğar

    2015-02-01

    Full Text Available The aim of this study was to evaluate for the cytotoxicity, genotoxicity and antioxidant/oxidant activity of GYZ on human peripheral blood lymphocytes (PBLs. Guaiazulene (GYZ was added into culture tubes at various concentrations (0-400 µg/mL-1. Cytotoxicity against the human lymphocytes cultures was examined by lactate dehydrogenase (LDH release assay. The proliferative response was estimated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT assay. Antioxidant/oxidant activity was evaluated by measuring the total oxidant status (TOS and total antioxidant capacity (TAC levels. Micronucleus (MN and chromosomal aberration (CA tests were used in genotoxicity studies. The results showed that GYZ caused cytotoxicity in the PBLs at high concentrations, but TOS level were not affected, while the level of TAC was significantly increased. GYZ also did not induce chromosomal aberrations when compared to that of the control group. Results this study clearly revealed that GYZ was not genotoxic and also increased the capacity of the antioxidant in the culture of human PBL cells. This report is first report on the impact of GYZ on human PBL cells.

  4. Cyto- and genotoxic profile of groundwater used as drinking water supply before and after disinfection.

    Science.gov (United States)

    Pellacani, C; Cassoni, F; Bocchi, C; Martino, A; Pinto, G; Fontana, F; Furlini, M; Buschini, A

    2016-12-01

    The assessment of the toxicological properties of raw groundwater may be useful to predict the type and quality of tap water. Contaminants in groundwater are known to be able to affect the disinfection process, resulting in the formation of substances that are cytotoxic and/or genotoxic. Though the European directive (98/83/EC, which establishes maximum levels for contaminants in raw water (RW)) provides threshold levels for acute exposure to toxic compounds, the law does not take into account chronic exposure at low doses of pollutants present in complex mixture. The purpose of this study was to evaluate the cyto- and genotoxic load in the groundwater of two water treatment plants in Northern Italy. Water samples induced cytotoxic effects, mainly observed when human cells were treated with RW. Moreover, results indicated that the disinfection process reduced cell toxicity, independent of the biocidal used. The induction of genotoxic effects was found, in particular, when the micronucleus assay was carried out on raw groundwater. These results suggest that it is important to include bio-toxicological assays as additional parameters in water quality monitoring programs, as their use would allow the evaluation of the potential risk of groundwater for humans.

  5. Investigating the embryo/larval toxic and genotoxic effects of {gamma} irradiation on zebrafish eggs

    Energy Technology Data Exchange (ETDEWEB)

    Simon, O., E-mail: olivier.simon@irsn.fr [Laboratoire de Radioecologie et d' Ecotoxicologie, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat 186, BP3, 13115 Saint-Paul-lez-Durance Cedex (France); Massarin, S. [Laboratoire de Modelisation Environnementale, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat 159, BP3, 13115 Saint-Paul-lez-Durance Cedex (France); Coppin, F. [Laboratoire de Radioecologie et d' Ecotoxicologie, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat 186, BP3, 13115 Saint-Paul-lez-Durance Cedex (France); Hinton, T.G. [Service d' Etude du Comportement des Radionucleides dans les Ecosystemes, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat 159, BP3, 13115 Saint-Paul-lez-Durance Cedex (France); Gilbin, R. [Laboratoire de Radioecologie et d' Ecotoxicologie, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat 186, BP3, 13115 Saint-Paul-lez-Durance Cedex (France)

    2011-11-15

    Eggs/larval of freshwater fish (Danio rerio) were exposed to low dose rates of external gamma radiation (from 1 to 1000 mGy d{sup -1}) over a 20-day period, with the objective of testing the appropriateness of the 10 mGy d{sup -1} guideline suggested by the IAEA. The present study examines different endpoints, mortality and hatching time and success of embryos as well as the genotoxicity of {gamma}-irradiations (after 48 h). The 20-day embryo-larval bioassay showed an enhanced larval resistance to starvation after chronic exposure to {gamma} irradiation (from low 1 mGy d{sup -1} to high dose rate 1000 mGy d{sup -1}) and an acceleration in hatching time. Gamma irradiation led to increased genotoxic damage Ito zebrafish egg (40-50% DNA in tail in Comet assay) from the lowest dose rate (1 mGy d{sup -1}). Possible mechanisms of {gamma} radiotoxicity and implications for radioprotection are discussed. - Highlights: > Relevant information on the {gamma} radiation impact on early life stage biota is scarce. > The eggs of zebrafish Danio rerio were selected as biological model. > We test the appropriateness of the 10 mGy d{sup -1} guideline (IAEA). > We observed effects measured at individual levels (starvation, hatching time). > Chronic gamma irradiation led to increased genotoxic damage to zebrafish egg. > {gamma} radiotoxicity mechanisms and implications for radioprotection are discussed.

  6. Potential genotoxic and cytotoxicity of emamectin benzoate in human normal liver cells.

    Science.gov (United States)

    Zhang, Zhijie; Zhao, Xinyu; Qin, Xiaosong

    2017-10-10

    Pesticide residue inducing cancer-related health problems draw people more attention recently. Emamectin benzoate (EMB) has been widely used in agriculture around the world based on its specificity targets. Although potential risk and the molecular mechanism of EMB toxicity to human liver has not been well-characterized. Unlike well-reported toxicity upon central nervous system, potential genotoxic and cytotoxicity of EMB in human liver cell was ignored and very limited. In this study, we identify genotoxicity and cytotoxicity of EMB to human normal liver cells (QSG7701 cell line) in vitro . We demonstrate that EMB inhibited the viability of QSG7701 cells and induced the DNA damage. Established assays of cytotoxicity were performed to characterize the mechanism of EMB toxicity on QSG7701 cells. Typical chromatin condensation and DNA fragmentation indicated the apoptosis of QSG7701 cells induced by EMB. And the intracellular biochemical results demonstrated that EMB-enhanced apoptosis of QSG7701 cells concurrent with generated ROS, a loss of mitochondrial membrane potential, the cytochrome-c release, up regulate the Bax/Bcl-2 and the activation of caspase-9/-3. Our results of EMB induces the death of QSG7701 cells maybe via mitochondrial-mediated intrinsic apoptotic pathways would contribute to promote the awareness of EMB as an extensive used pesticide to human being effects and reveal the underlying mechanisms of potential genotoxic.

  7. In Vitro Evaluation of Genotoxic Effects under Magnetic Resonant Coupling Wireless Power Transfer

    Directory of Open Access Journals (Sweden)

    Kohei Mizuno

    2015-04-01

    Full Text Available Wireless power transfer (WPT technology using the resonant coupling phenomenon has been widely studied, but there are very few studies concerning the possible relationship between WPT exposure and human health. In this study, we investigated whether exposure to magnetic resonant coupling WPT has genotoxic effects on WI38VA13 subcloned 2RA human fibroblast cells. WPT exposure was performed using a helical coil-based exposure system designed to transfer power with 85.4% efficiency at a 12.5-MHz resonant frequency. The magnetic field at the positions of the cell culture dishes is approximately twice the reference level for occupational exposure as stated in the International Commission on Non-Ionizing Radiation Protection (ICNIRP guidelines. The specific absorption rate at the positions of the cell culture dishes matches the respective reference levels stated in the ICNIRP guidelines. For assessment of genotoxicity, we studied cell growth, cell cycle distribution, DNA strand breaks using the comet assay, micronucleus formation, and hypoxanthine-guanine phosphoribosyltransferase (HPRT gene mutation, and did not detect any significant effects between the WPT-exposed cells and control cells. Our results suggest that WPT exposure under the conditions of the ICNIRP guidelines does not cause detectable cellular genotoxicity.

  8. Can Genotoxic Effect be Model Dependent in Allium Test?-An Evidence

    Directory of Open Access Journals (Sweden)

    Hemant Singh Rathore

    2010-07-01

    Full Text Available Genotoxicity of peracetic acid (PAA has been assessed in two models (protocols of Allium cepa conducting two sets of experiments to know whether the results would be model dependent. One experiment was set as per Fiskesjo's model in which Allium cepa bulbs were grown in five concentrations of peracetic acid (0.039, 0.078, 0.156, 0.312 and 0.625 ppm in tap water. Another experiment was set as per Rank and Nielson's model in which Allium cepa bulbs were first grown in tap water for 24 hours and were then further grown in the same concentrations of peracetic acid as in earlier model. Genotoxic effects of peracetic acid were assessed in both models using usual parameters i.e. shape, colour and length of root tips, mitotic index, chromosomal aberrations and cell death. Magnitude of effect differed significantly in both models. More severe genotoxic effects could be seen in Fiskesjo's model. It is suggested that root primordial cells were in G0 state in Fiskesjo's model, which presumably lacked their defense system, hence were more prone to peracetic acid toxicity. Mitotically dividing root cells in Rank and Nielsen's model were equipped with antioxidant system and were more resistant to peracetic acid

  9. Evaluation of genotoxic effect of silver nanoparticles (Ag-Nps) in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Tavares, Priscila; Balbinot, Fernanda; Martins de Oliveira, Hugo; Elibio Fagundes, Gabriela [PPGCS, Universidade do Extremo Sul Catarinense, Laboratorio de Biologia Celular e Molecular (Brazil); Venancio, Mireli; Vieira Ronconi, Joao Vitor; Merlini, Aline [Universidade do Extremo Sul Catarinense, Laboratorio de Sintese de Complexos Multifuncionais (Brazil); Streck, Emilio L. [Programa de Pos-Graduacao em Ciencias da Saude, Unidade Academica de Ciencias da Saude, Universidade do Extremo Sul Catarinense, Laboratorio de Fisiopatologia Experimental (Brazil); Marques da Silva, Paula [Universidade do Extremo Sul Catarinense, Laboratorio de Sintese de Complexos Multifuncionais (Brazil); Moraes de Andrade, Vanessa, E-mail: vmoraesdeandrade@yahoo.com.br [PPGCS, Universidade do Extremo Sul Catarinense, Laboratorio de Biologia Celular e Molecular (Brazil)

    2012-03-15

    Silver nanoparticles (Ag-NPs) are the most prominent nanoproducts. Due to their antimicrobial activity, they have been incorporated in different materials, such as catheters, clothes, electric home appliance, and many others. The genotoxicity of Ag-NPs (5-45 nm), in different concentrations and times of exposure, was evaluated by the comet assay in in vitro and in vivo conditions, respectively, using human peripheral blood and Swiss mice. The results showed the genotoxic effect of Ag-NPs in vitro, in all the doses tested in the initial hour of exposure, possibly through the reactive oxygen species generation. Nevertheless, the values for this damage decrease with time, indicating that the DNA may have been restored by the repair system. In the in vivo conditions, we found no genotoxicity of Ag-NPs in any hour of exposure and any dose investigated, which can be attributed to the activation of a cellular antioxidant network and the hydrophobic nature of Ag-NPs. Now, it is absolutely necessary to investigate the role of Ag-NPs in different cell lines in vivo.

  10. Sensitivity of Bidens laevis L. to mutagenic compounds. Use of chromosomal aberrations as biomarkers of genotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Perez, D.J. [Laboratorio de Genetica, Estacion Experimental Agropecuaria Balcarce (INTA), Facultad de Ciencias Agrarias, UNMdP, CC 276, 7620 Balcarce (Argentina); Laboratorio de Ecotoxicologia, Departamento de Ciencias Marinas, Facultad de Ciencias Exactas y Naturales, UNMdP, Funes 3350, 7600 Mar del Plata (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Rivadavia 1917, 1033 Buenos Aires (Argentina); Lukaszewicz, G. [Laboratorio de Ecotoxicologia, Departamento de Ciencias Marinas, Facultad de Ciencias Exactas y Naturales, UNMdP, Funes 3350, 7600 Mar del Plata (Argentina); Menone, M.L., E-mail: lujanm@mdp.edu.a [Laboratorio de Ecotoxicologia, Departamento de Ciencias Marinas, Facultad de Ciencias Exactas y Naturales, UNMdP, Funes 3350, 7600 Mar del Plata (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Rivadavia 1917, 1033 Buenos Aires (Argentina); Camadro, E.L. [Laboratorio de Genetica, Estacion Experimental Agropecuaria Balcarce (INTA), Facultad de Ciencias Agrarias, UNMdP, CC 276, 7620 Balcarce (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Rivadavia 1917, 1033 Buenos Aires (Argentina)

    2011-01-15

    The wetland macrophyte Bidens laevis possesses suitable cytological characteristics for genotoxicity testing. To test its sensitivity as compared to terrestrial plants species currently in use in standardized assays, Methyl Methanesulfonate (MMS), N-ethyl-N-nitrosourea (ENU) and Maleic Hydrazide (HM) were used. On the other hand, the insecticide Endosulfan (ES) - an environmentally relevant contaminant - was assayed in seeds and two-month old plants. Mitotic Index (MI), frequency of Chromosome Aberrations in Anaphase-Telophase (CAAT) and frequency of Abnormal Metaphases (AM) were analyzed. MH, MMS and ENU caused a significant decrease of the MI. MMS was aneugenic whereas MH and ENU were both aneugenic and clastogenic. ES caused a significant concentration-dependent increase of total- and aneugenic-CAAT in roots and a significant high frequency of AM at high concentrations. Because of its sensitivity to mutagenic substances, B. laevis can be regarded as a reliable and convenient species for genotoxicity assays especially if aquatic contaminants are evaluated. - The wetland macrophyte Bidens laevis is sensitive to genotoxic compounds similarly to terrestrial standardized species.

  11. Applicability of in silico genotoxicity models on food and feed ingredients.

    Science.gov (United States)

    Vuorinen, Anna; Bellion, Phillip; Beilstein, Paul

    2017-11-01

    Evaluation of the genotoxic potential of food and feed ingredients is required in the development of new substances and for their registration. In addition to in vitro and in vivo assays, in silico tools such as expert alert-based and statistical models can be used for data generation. These in silico models are commonly used among the pharmaceutical industry, whereas the food industry has not widely adopted them. In this study, the applicability of in silico tools for predicting genotoxicity was evaluated, with a focus on bacterial mutagenicity, in vitro and in vivo chromosome damage assays. For this purpose, a test set of 27 food and feed ingredients including vitamins, carotenoids, and nutraceuticals with experimental genotoxicity data was constructed from proprietary data. This dataset was run through multiple models and the model applicability was analyzed. The compounds were generally within the applicability domain of the models and the models predicted the compounds correctly in most of the cases. Although the regulatory acceptance of in silico tools as single data source is still limited, the models are applicable and can be used in the safety evaluation of food and feed ingredients. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Dichlorophen and Dichlorovos mediated genotoxic and cytotoxic assessment on root meristem cells of Allium cepa

    Directory of Open Access Journals (Sweden)

    Sibhghatulla Shaikh

    2012-06-01

    Full Text Available Plants are direct recipients of agro – toxics and therefore important materials for assessing environmental chemicals for genotoxicity. The meristematic mitotic cell of Allium cepa is an efficient cytogenetic material for chromosome aberration assay on environmental pollutants. Onion root tips were grown on moistened filter paper in petri dish at room temperature. Germinated root tips were then exposed to three concentrations of each pesticide for 24 h. About 1 – 2 mm length of root tip was cut, fixed in cornoy’s fixative, hydrolyzed in warm 1 N HCL, stained with acetocarmine and squashed on glass slide. About 3000 cells were scored and classified into interphase and normal or aberrant division stage. Cytotoxicity was determined by comparing the mitotic index (MI of treated cells with that of the negative control. The MI of cells treated with Dichlorophen and Dichlorovos at one or more concentration was half or less than that of control are said to be cytotoxic. Genotoxicity was measured by comparing the number of cells/1000 in aberrant division stages at each dose with the negative control using Mann – Whitney U test. Both Dichlorophen and Dichlorovos are genotoxic at higher concentrations i.e. 0.001%, 0.002% and 0.028%, 0.056% inducing chromosome fragment, chromosome lagging and bridges, stick chromosome and multipolar anaphase.

  13. Genotoxic effects of water pollution on two fish species living in Karasu River, Erzurum, Turkey.

    Science.gov (United States)

    Yazıcı, Zehra; Sişman, Turgay

    2014-11-01

    Karasu River, which is the only river in the Erzurum plain, is the source of the Euphrates River (Eastern Anatolia of Turkey). The river is in a serious environmental situation as a result of pollution by agricultural and industrial sewage and domestic discharges. The present study aims to evaluate genotoxic effects of toxic metals in chub, Leuciscus cephalus, and transcaucasian barb, Capoeta capoeta, collected from contaminated site of the Karasu River, in comparison with fish from an unpolluted reference site. Heavy metal concentrations in surface water of the river were determined. The condition factor (CF) was taken as a general biomarker of the health of the fish, and genotoxicity assays such as micronucleus (MN) and other nuclear abnormalities (NA) were carried out on the fish species studied. MN and NA such as kidney-shaped nucleus, notched nucleus, binucleated, lobed nucleus, and blebbed nucleus were assessed in peripheral blood erythrocytes, gill epithelial cells, and liver cells of the fish. A significant decrease in CF values associated with a significant elevation in MN and NA frequencies was observed in fish collected from the polluted sites compared with those from the reference site. Results of the current study show the significance of integrating a set of biomarkers to identify the effects of anthropogenic pollution. High concentrations of heavy metals have a potential genotoxic effects, and the toxicity is possibly related to industrial, agricultural, and domestic activities.

  14. Acute genotoxicity analysis in vivo of the aqueous extract of Maytenus guyanensis Amazonian chichuá

    Directory of Open Access Journals (Sweden)

    Dionatas Ulises de Oliveira Meneguetti

    Full Text Available Abstract The species Maytenus guyanensis Klotzsch ex Reissek, Celastraceae, present a wide variety of possible pharmacological activities and its roots and stems are used by popular medicine in the western Amazon rainforest. Few studies have demonstrated the genotoxic safety of the popular use of this species, and owing to this, the present study aimed to perform an analysis of the acute genotoxicity in vivo of the aqueous extract of M. guyanensis. Male and female mice from Mus musculus species, of weights ranging from 20 to 40 g, organized in eight groups with different treatments were used. The aqueous extracts of the bark of M. guyanensis were administered orally by gavage with 0.1 ml of the test substance per 10 g of the animal, followed by performance of comet assay in peripheral blood, PCE/NCE correlation and occurrence of micronuclei in the bone marrow. It was found that the aqueous extract of M. guyanensis, with ten times higher concentration than those used in ethnopharmacology, did not present genotoxic effect and, moreover, it has antigenotoxic action in mice treated acutely. Further studies regarding bioaccumulation and chronic effects of this species are suggested, in order to improve the understanding of its mechanism of action, ensuring the efficacy and safety of its utilization and developing phytotherapics and drugs.

  15. Evaluation of Hypoglycemic and Genotoxic Effect of Polyphenolic Bark Extract from Quercus sideroxyla

    Directory of Open Access Journals (Sweden)

    Marcela Soto-García

    2016-01-01

    Full Text Available Quercus sideroxyla is a wood species whose bark has phenolic compound and should be considered to be bioactive; the hypoglycemic and genotoxic properties of Q. sideroxyla bark were evaluated in this study. Total phenolic compound was determined in crude extract (CE and organic extract (OE. The OE has the highest amount of phenols (724.1±12.0 GAE/g. Besides, both CE and OE demonstrated effect over the inhibition of α-amylase in vitro. Hypoglycemic activity was assessed by glucose tolerance curve and the area under curve (UAC; OE showed the highest hypoglycemic activity. In addition, diabetes was induced by streptozotocin (65 mg/kg and the extracts (50 mg/kg were administered for 10 days; OE showed hypoglycemic effect compared with diabetic control and decreased hepatic lipid peroxidation. Acute toxicity and genotoxicity were evaluated in CE; results of acute toxicity did not show any mortality. Besides, the comet assay showed that CE at a dose of 100 mg/kg did not show any genotoxic effect when evaluated at 24 h, whereas it induced slight damage at 200 mg/kg, with the formation of type 1 comets.

  16. Bacterial Composition, Genotoxicity, and Cytotoxicity of Fecal Samples from Individuals Consuming Omnivorous or Vegetarian Diets

    Science.gov (United States)

    Federici, Ermanno; Prete, Roberta; Lazzi, Camilla; Pellegrini, Nicoletta; Moretti, Massimo; Corsetti, Aldo; Cenci, Giovanni

    2017-01-01

    This study analyzes the composition of viable fecal bacteria and gut toxicology biomarkers of 29 healthy volunteers, who followed omnivorous, lacto-ovo-vegetarian, or vegan diets. In particular, the research was focused on the prevalence of some representative viable bacteria from the four dominant phyla (Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria) commonly present in human feces, in order to evaluate the relationship between microorganisms selected by the habitual dietary patterns and the potential risk due to fecal water (FW) genotoxicity and cytotoxicity, considered as biomarkers for cancer risk and protective food activity. The relative differences of viable bacteria among dietary groups were generally not statistically significant. However, compared to omnivores, lacto-ovo-vegetarians showed low levels of total anaerobes. Otherwise, vegans showed total anaerobes counts similar to those of omnivores, but with lower number of bifidobacteria and the highest levels of bacteria from the Bacteroides–Prevotella genera. FW genotoxicity of lacto-ovo-vegetarians resulted significantly lower either in relation to that of omnivores and vegans. Lacto-ovo-vegetarians also showed the lowest levels of cytotoxicity, while the highest were found for vegans. These results highlighted that lacto-ovo-vegetarian diet was particularly effective in a favorable modulation of microbial activity, thus contributing to a significant reduction of the genotoxic and cytotoxic risk in the gut. PMID:28293225

  17. The use of genotoxicity biomarkers in molecular epidemiology: applications in environmental, occupational and dietary studies

    Directory of Open Access Journals (Sweden)

    Carina Ladeira

    2017-08-01

    Full Text Available Molecular epidemiology is an approach increasingly used in the establishment of associations between exposure to hazardous substances and development of disease, including the possible modulation by genetic susceptibility factors. Environmental chemicals and contaminants from anthropogenic pollution of air, water and soil, but also originating specifically in occupational contexts, are potential sources of risk of development of disease. Also, diet presents an important role in this process, with some well characterized associations existing between nutrition and some types of cancer. Genotoxicity biomarkers allow the detection of early effects that result from the interaction between the individual and the environment; they are therefore important tools in cancer epidemiology and are extensively used in human biomonitoring studies. This work intends to give an overview of the potential for genotoxic effects assessment, specifically with the cytokinesis blocked micronucleus assay and comet assay in environmental and occupational scenarios, including diet. The plasticity of these techniques allows their inclusion in human biomonitoring studies, adding important information with the ultimate aim of disease prevention, in particular cancer, and so it is important that they be included as genotoxicity assays in molecular epidemiology.

  18. Bacterial Composition, Genotoxicity, and Cytotoxicity of Fecal Samples from Individuals Consuming Omnivorous or Vegetarian Diets.

    Science.gov (United States)

    Federici, Ermanno; Prete, Roberta; Lazzi, Camilla; Pellegrini, Nicoletta; Moretti, Massimo; Corsetti, Aldo; Cenci, Giovanni

    2017-01-01

    This study analyzes the composition of viable fecal bacteria and gut toxicology biomarkers of 29 healthy volunteers, who followed omnivorous, lacto-ovo-vegetarian, or vegan diets. In particular, the research was focused on the prevalence of some representative viable bacteria from the four dominant phyla (Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria) commonly present in human feces, in order to evaluate the relationship between microorganisms selected by the habitual dietary patterns and the potential risk due to fecal water (FW) genotoxicity and cytotoxicity, considered as biomarkers for cancer risk and protective food activity. The relative differences of viable bacteria among dietary groups were generally not statistically significant. However, compared to omnivores, lacto-ovo-vegetarians showed low levels of total anaerobes. Otherwise, vegans showed total anaerobes counts similar to those of omnivores, but with lower number of bifidobacteria and the highest levels of bacteria from the Bacteroides-Prevotella genera. FW genotoxicity of lacto-ovo-vegetarians resulted significantly lower either in relation to that of omnivores and vegans. Lacto-ovo-vegetarians also showed the lowest levels of cytotoxicity, while the highest were found for vegans. These results highlighted that lacto-ovo-vegetarian diet was particularly effective in a favorable modulation of microbial activity, thus contributing to a significant reduction of the genotoxic and cytotoxic risk in the gut.

  19. Genotoxic Effects of Superconducting Static Magnetic Fields (SMFs) on Wheat (Triticum aestivum) Pollen Mother Cells (PMCs)

    Science.gov (United States)

    Zhang, Pingping; Yin, Ruochun; Chen, Zhiyou; Wu, Lifang; Yu, Zengliang

    2007-04-01

    The effects of superconducting static magnetic fields (SMFs) on the pollen mother cells (PMCs) of wheat were investigated in order to evaluate the possible genotoxic effect of such non-ionizing radiation. The seeds of wheat were exposed to static magnetic fields with either different magnetic flux densities (0, 1, 3, 5 and 7 Tesla) for 5 h or different durations (1, 3 and 5 h) at a magnetic flux density of 7 Tesla. The seeds were germinated at 23oC after exposure and the seedlings were transplanted into the field. The PMCs from young wheat ears were taken and slides were made following the conventional method. The genotoxic effect was evaluated in terms of micronucleus (MN), chromosomal bridge, lagging chromosome and fragments in PMCs. Although the exposed groups of a low field intensity (below 5 Tesla) showed no statistically significant difference in the aberration frequency compared with the unexposed control groups and sham exposed groups, a significant increase in the chromosomal bridge, lagging chromosome, triple-polar segregation or micronucleus was observed at a field strength of 5 Tesla or 7 Tesla, respectively. The analysis of dose-effect relationships indicated that the increased frequency of meiotic abnormal cells correlated with the flux density of the magnetic field and duration, but no linear relationship was observed. Such statistically significant differences indicated a potential genotoxic effect of high static magnetic fields above 5 T.

  20. The Cosmetics Europe strategy for animal-free genotoxicity testing: project status up-date.

    Science.gov (United States)

    Pfuhler, S; Fautz, R; Ouedraogo, G; Latil, A; Kenny, J; Moore, C; Diembeck, W; Hewitt, N J; Reisinger, K; Barroso, J

    2014-02-01

    The Cosmetics Europe (formerly COLIPA) Genotoxicity Task Force has driven and funded three projects to help address the high rate of misleading positives in in vitro genotoxicity tests: The completed "False Positives" project optimized current mammalian cell assays and showed that the predictive capacity of the in vitro micronucleus assay was improved dramatically by selecting more relevant cells and more sensitive toxicity measures. The on-going "3D skin model" project has been developed and is now validating the use of human reconstructed skin (RS) models in combination with the micronucleus (MN) and Comet assays. These models better reflect the in use conditions of dermally applied products, such as cosmetics. Both assays have demonstrated good inter- and intra-laboratory reproducibility and are entering validation stages. The completed "Metabolism" project investigated enzyme capacities of human skin and RS models. The RS models were shown to have comparable metabolic capacity to native human skin, confirming their usefulness for testing of compounds with dermal exposure. The program has already helped to improve the initial test battery predictivity and the RS projects have provided sound support for their use as a follow-up test in the assessment of the genotoxic hazard of cosmetic ingredients in the absence of in vivo data. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Genotoxic potential evaluation of a cosmetic insoluble substance by the micronuclei assay.

    Science.gov (United States)

    Dayan, N; Shah, V; Minko, T

    2011-01-01

    An optical brightener (OB) powder (INCI: sodium silicoaluminate (and) glycidoxypropyl trimethyloxysilane/PEI-250 cross fluorescent brightener 230 salt (and) polyvinylalcohol crosspolymer) that is used in cosmetic facial products was tested for its genotoxic potential using the micronuclei test (MNT). It is a solid dry powder with an average size of 5 microns that is insoluble but dispersible in water. This study describes the exposure of cell culture to positive controls with and without enzymatic activation and to the test compound in different concentrations. We evaluated three end points: microscopic observation and quantification of micronuclei formation, and cell viability and proliferation. Both positive controls induced significant changes that were observed under the microscope and quantified. Based on its chemical nature, it was not anticipated that the test substance will degrade under the conditions of the experiments. However, the test is required to make sure that when solublized, impurities that may be present, even at trace levels, will not induce a genotoxic effect. The test compound did not promote micronuclei formation or change the viability or proliferation rate of cells. During this study we faced challenges such as solubilization and correlating viability data to genotoxicity data. These are described in the body of the paper. We believe that with the emergence of the 7(th) European amendment that bans animal testing, sharing these data and the study protocol serves as a key in building the understanding of the utilization of in vitro studies in the safety assessment of cosmetic ingredients.

  2. Sensitivity of Bidens laevis L. to mutagenic compounds. Use of chromosomal aberrations as biomarkers of genotoxicity

    International Nuclear Information System (INIS)

    Perez, D.J.; Lukaszewicz, G.; Menone, M.L.; Camadro, E.L.

    2011-01-01

    The wetland macrophyte Bidens laevis possesses suitable cytological characteristics for genotoxicity testing. To test its sensitivity as compared to terrestrial plants species currently in use in standardized assays, Methyl Methanesulfonate (MMS), N-ethyl-N-nitrosourea (ENU) and Maleic Hydrazide (HM) were used. On the other hand, the insecticide Endosulfan (ES) - an environmentally relevant contaminant - was assayed in seeds and two-month old plants. Mitotic Index (MI), frequency of Chromosome Aberrations in Anaphase-Telophase (CAAT) and frequency of Abnormal Metaphases (AM) were analyzed. MH, MMS and ENU caused a significant decrease of the MI. MMS was aneugenic whereas MH and ENU were both aneugenic and clastogenic. ES caused a significant concentration-dependent increase of total- and aneugenic-CAAT in roots and a significant high frequency of AM at high concentrations. Because of its sensitivity to mutagenic substances, B. laevis can be regarded as a reliable and convenient species for genotoxicity assays especially if aquatic contaminants are evaluated. - The wetland macrophyte Bidens laevis is sensitive to genotoxic compounds similarly to terrestrial standardized species.

  3. Protective Effect of Melatonin Against Mitomycin C-Induced Genotoxic Damage in Peripheral Blood of Rats

    Directory of Open Access Journals (Sweden)

    S. Ortega-Gutiérrez

    2009-01-01

    Full Text Available Mitomycin C (MMC generates free radicals when metabolized. We investigated the effect of melatonin against MMC-induced genotoxicity in polychromatic erythrocytes and MMC-induced lipid peroxidation in brain and liver homogenates. Rats (N = 36 were classified into 4 groups: control, melatonin, MMC, and MMC + melatonin. Melatonin and MMC doses of 10 mg/kg and 2 mg/kg, respectively, were injected intraperitoneally. Peripheral blood samples were collected at 0, 24, 48, 72, and 96 hours posttreatment and homogenates were obtained at 96 hours posttreatment. The number of micronucleated polychromatic erythrocytes (MN-PCE per 1000 PCE was used as a genotoxic marker. Malondialdehyde (MDA plus 4-hydroxyalkenal (4-HDA levels were used as an index of lipid peroxidation. The MMC group showed a significant increase in MN-PCE at 24, 48, 72, and 96 hours that was significantly reduced with melatonin begin coadministrated. No significant differences were found in lipid peroxidation. Our results indicate that MMC-induced genotoxicity can be reduced by melatonin.

  4. Genotoxicity and mutagenicity of Echinodorus macrophyllus (chapéu-de-couro extracts

    Directory of Open Access Journals (Sweden)

    Leonardo S. Vidal

    2010-01-01

    Full Text Available Echinodorus macrophyllus, commonly known as chapéu-de-couro, is a medicinal plant used in folk medicine to treat inflammation and rheumatic diseases. In this work, we used short-term bacterial assays based on the induction of SOS functions to examine the genotoxicity and mutagenicity of an aqueous extract of E. macrophyllus leaves. Whole extract and an ethyl acetate fraction showed similar genotoxicity and caused an ~70-fold increase in lysogenic induction. The extract also gave a positive result in the SOS chromotest with an increase of 12-fold in β-Galactosidase enzymatic units. There was a strong trend towards base substitutions and frameshifts at purine sites in the mutations induced by the extract in Escherichia coli (CC103 and CC104 strains and Salmonella typhimurium test strains (22-fold increase in histidine revertants in TA98 strain. Since reactive oxygen species may be implicated in aging process and in degenerative diseases, we used antioxidant compounds as catalase, thiourea and dipyridyl in the lysogenic induction test. All this compounds were able to reduce the induction factor observed in the treatment with chapéu-de-couro, thus suggesting that the genotoxicity and mutagenicity were attributable to the production of reactive oxygen species that targeted DNA purines.

  5. Silica nanoparticles and biological dispersants: genotoxic effects on A549 lung epithelial cells

    Science.gov (United States)

    Brown, David M.; Varet, Julia; Johnston, Helinor; Chrystie, Alison; Stone, Vicki

    2015-10-01

    Silica nanoparticle exposure could be intentional (e.g. medical application or food) or accidental (e.g. occupational inhalation). On entering the body, particles become coated with specific proteins depending on the route of entry. The ability of silica particles of different size and charge (non-functionalized 50 and 200 nm and aminated 50 and 200 nm) to cause genotoxic effects in A549 lung epithelial cells was investigated. Using the modified comet assay and the micronucleus assay, we examined the effect of suspending the particles in different dispersion media [RPMI or Hanks' balanced salt solution (HBSS), supplemented with bovine serum albumin (BSA), lung lining fluid (LLF) or serum] to determine if this influenced the particle's activity. Particle characterisation suggested that the particles were reasonably well dispersed in the different media, with the exception of aminated 50 nm particles which showed evidence of agglomeration. Plain 50, 200 nm and aminated 50 nm particles caused significant genotoxic effects in the presence of formamidopyrimidine-DNA glycosylase when dispersed in HBSS or LLF. These effects were reduced when the particles were dispersed in BSA and serum. There was no significant micronucleus formation produced by any of the particles when suspended in any of the dispersants. The data suggest that silica particles can produce a significant genotoxic effect according to the comet assay in A549 cells, possibly driven by an oxidative stress-dependent mechanism which may be modified depending on the choice of dispersant employed.

  6. ROS-mediated genotoxicity of asbestos-cement in mammalian lung cells in vitro

    Directory of Open Access Journals (Sweden)

    Rödelsperger Klaus

    2005-10-01

    Full Text Available Abstract Asbestos is a known carcinogen and co-carcinogen. It is a persisting risk in our daily life due to its use in building material as asbestos-cement powder. The present study done on V79-cells (Chinese hamster lung cells demonstrates the cytotoxic and genotoxic potential of asbestos-cement powder (ACP in comparison with chrysotile asbestos. A co-exposure of chrysotile and ACP was tested using the cell viability test and the micronucleus assay. The kinetochore analysis had been used to analyse the pathway causing such genotoxic effects. Thiobarbituric acid-reactive substances were determined as evidence for the production of reactive oxygen species. Both, asbestos cement as well as chrysotile formed micronuclei and induced loss of cell viability in a concentration- and time- dependent way. Results of TBARS analysis and iron chelator experiments showed induction of free radicals in ACP- and chrysotile exposed cultures. CaSO4 appeared to be a negligible entity in enhancing the toxic potential of ACP. The co-exposure of both, ACP and chrysotile, showed an additive effect in enhancing the toxicity. The overall study suggests that asbestos-cement is cytotoxic as well as genotoxic in vitro. In comparison to chrysotile the magnitude of the toxicity was less, but co-exposure increased the toxicity of both.

  7. Analysis of Aloe vera cytotoxicity and genotoxicity associated with endodontic medication and laser photobiomodulation.

    Science.gov (United States)

    Carvalho, Nayane Chagas; Guedes, Simone Alves Garcez; Albuquerque-Júnior, Ricardo Luiz Cavalcanti; de Albuquerque, Diana Santana; de Souza Araújo, Adriano Antunes; Paranhos, Luiz Renato; Camargo, Samira Esteves Afonso; Ribeiro, Maria Amália Gonzaga

    2018-01-01

    This study aims to evaluate, in vitro, the effect of Aloe vera associated with endodontic medication, with or without laser photobiomodulation (FTL) irradiation in FP6 human pulp fibroblasts. The materials were divided into eight groups: CTR - control; CL - FTL alone; AA - Aloe vera with distilled water; AL - Aloe vera with distilled water and FTL; HA - calcium hydroxide P.A. with distilled water; HL - calcium hydroxide P.A. with distilled water and FTL; HAA - calcium hydroxide P.A. with Aloe vera and distilled water; HAL - calcium hydroxide P.A. with Aloe vera, distilled water, and FTL. The cytotoxicity was evaluated by MTT assay at 24, 48, and 72h and the genotoxicity by micronucleus test assay. This study was performed in triplicate. Data obtained in both tests were statistically analyzed by ANOVA and Tukey's tests (p≤0.05). Group AA presented high genotoxicity and low cytotoxicity. After 24, 48, and 72h, the group HAA significantly reduced the cell viability. Interaction with FTL showed slightly increase cell viability after 24 and 48h in groups CL and HL (pAloe vera allowed higher cell viability in human pulp fibroblasts in the presence of calcium hydroxide or with FTL separately, but genotoxicity increased in these associations. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. UVA/UVB-induced genotoxicity and lesion repair in Colossoma macropomum and Arapaima gigas Amazonian fish.

    Science.gov (United States)

    Groff, Aline Aparecida; da Silva, Juliana; Nunes, Emilene A; Ianistcki, Martus; Guecheva, Temenouga N; de Oliveira, Alzira Miranda; de Oliveira, Christiane Patrícia Feitosa; Val, Adalberto Luis; Henriques, João A P

    2010-05-03

    Ultraviolet radiation is known to cause adverse effects to aquatic species and aquatic environments. The fish Colossoma macropomum (tambaqui) and Arapaima gigas (pirarucu) live in the Amazon basin, near the Equator, and thus receive high intensity of ultraviolet radiation. Deforestation further aggravates the situation by reducing shade at ground level. The aim of this study was to evaluate the genotoxic effects of UVA and UVB radiation on erythrocytes of tambaqui and pirarucu fish using Micronuclei test and Comet assay. Our study showed that UV radiation caused DNA damage in both species as detected by Comet assay. In addition, there were differences in response to genotoxicity between both species, which are possibly related to their evolutionary history. Tambaqui fish exposed to ultraviolet radiation for different periods presented clear dose-response in DNA damage profile. Significant damage repair was observed 24h after cessation of ultraviolet radiation exposure. At the test conditions used, no significant increase in micronucleated cells was observed in tambaqui and pirarucu fish. Tambaqui proved to be more sensitive to ultraviolet radiation than Pirarucu, as detected by Comet assay, showing statistically higher baseline DNA damage. The present results demonstrated that alkaline Comet assay was very sensitive for detecting the UV-induced genotoxicity during the short exposure period in our study. In addition, the present study also suggests that tambaqui and pirarucu fish are useful sentinel organisms, as their UV sensitivity allows them to be effective monitors of biological hazards in the Amazon region. Copyright 2010 Elsevier B.V. All rights reserved.

  9. [Study on the chemical components of edible oil fume in kitchen and its genotoxity on Drosophila].

    Science.gov (United States)

    Li, S; Wang, Y; Zhang, J; Zhao, X

    1999-01-30

    To study the chemical components of the condensate of edible oil fume in kitchen and its genotoxicity on Drosophila. Analysis for the chemical components was carried out by gas chromatography and mass spectra (GC/MS) and its genotoxicity was studied by sex linked recessive lethal (SLRL) test in Drosophila. A total of 74 organic compounds were found in samples of condensed oil from the fume in kitchen. It included hydroxylic acids, hydrocarbons, alcohols, esters, aldehydes, ketones, aromatic compounds, and steroids, etc. The total mutagenicity rates in SLRL test induced by the samples at concentrations of 110,320 and 960 mg/L were 0.1732%, 0.4306% and 0.1707% respectively. The sterility rates of the first broods were 2.564%, 2.056% and 2.845% at above 3 concentrations respectively(P < 0.05, as compared with the control). The mutagenicity rate of the second brood at 320 mg/L was 0.530% and that of the third brood at 110 mg/L 0.540%(P < 0.001). Some of the compounds in the condensate of edible oil fume were proved to have high recessive lethal effect and genotoxic effect on the reproductive system of Drosophila.

  10. Comparative potency approach based on H2AX assay for estimating the genotoxicity of polycyclic aromatic hydrocarbons.

    Science.gov (United States)

    Audebert, M; Zeman, F; Beaudoin, R; Péry, A; Cravedi, J-P

    2012-04-01

    Polycyclic Aromatic Hydrocarbons (PAHs) constitute a family of over one hundred compounds and can generally be found in complex mixtures. PAHs metabolites cause DNA damage which can lead to the development of carcinogenesis. Toxicity assessment of PAH complex mixtures is currently expressed in terms of toxic equivalents, based on Toxicity Equivalent Factors (TEFs). However, the definition of new TEFs for a large number of PAH could overcome some limitations of the current method and improve cancer risk assessment. The current investigation aimed at deriving the relative potency factors of PAHs, based on their genotoxic effect measured in vitro and analyzed with mathematical models. For this purpose, we used a new genotoxic assay (γH2AX) with two human cell lines (HepG2 and LS-174T) to analyze the genotoxic properties of 13 selected PAHs at low doses after 24h treatment. The dose-response for genotoxic effects was modeled with a Hill model; equivalency between PAHs at low dose was assessed by applying constraints to the model parameters. In the two cell lines tested, we observed a clear dose-response for genotoxic effects for 11 tested compounds. LS-174T was on average ten times more sensitive than HepG2 towards PAHs regarding genotoxicity. We developed new TEFs, which we named Genotoxic Equivalent Factor (GEF). Calculated GEF for the tested PAHs were generally higher than the TEF usually used. Our study proposed a new in vitro based method for the establishment of relevant TEFs for PAHs to improve cancer risk assessment. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Size- and coating-dependent cytotoxicity and genotoxicity of silver nanoparticles evaluated using in vitro standard assays.

    Science.gov (United States)

    Guo, Xiaoqing; Li, Yan; Yan, Jian; Ingle, Taylor; Jones, Margie Yvonne; Mei, Nan; Boudreau, Mary D; Cunningham, Candice K; Abbas, Mazhar; Paredes, Angel M; Zhou, Tong; Moore, Martha M; Howard, Paul C; Chen, Tao

    2016-11-01

    The physicochemical characteristics of silver nanoparticles (AgNPs) may greatly alter their toxicological potential. To explore the effects of size and coating on the cytotoxicity and genotoxicity of AgNPs, six different types of AgNPs, having three different sizes and two different coatings, were investigated using the Ames test, mouse lymphoma assay (MLA) and in vitro micronucleus assay. The genotoxicities of silver acetate and silver nitrate were evaluated to compare the genotoxicity of nanosilver to that of ionic silver. The Ames test produced inconclusive results for all types of the silver materials due to the high toxicity of silver to the test bacteria and the lack of entry of the nanoparticles into the cells. Treatment of L5718Y cells with AgNPs and ionic silver resulted in concentration-dependent cytotoxicity, mutagenicity in the Tk gene and the induction of micronuclei from exposure to nearly every type of the silver materials. Treatment of TK6 cells with these silver materials also resulted in concentration-dependent cytotoxicity and significantly increased micronucleus frequency. With both the MLA and micronucleus assays, the smaller the AgNPs, the greater the cytotoxicity and genotoxicity. The coatings had less effect on the relative genotoxicity of AgNPs than the particle size. Loss of heterozygosity analysis of the induced Tk mutants indicated that the types of mutations induced by AgNPs were different from those of ionic silver. These results suggest that AgNPs induce cytotoxicity and genotoxicity in a size- and coating-dependent manner. Furthermore, while the MLA and in vitro micronucleus assay (in both types of cells) are useful to quantitatively measure the genotoxic potencies of AgNPs, the Ames test cannot.

  12. The comet assay in Environmental Risk Assessment of marine pollutants: applications, assets and handicaps of surveying genotoxicity in non-model organisms.

    Science.gov (United States)

    Martins, Marta; Costa, Pedro M

    2015-01-01

    Determining the genotoxic effects of pollutants has long been a priority in Environmental Risk Assessment (ERA) for coastal ecosystems, especially of complex areas such as estuaries and other confined waterbodies. The acknowledged link between DNA damage, mutagenicity and carcinogenicity to the exposure to certain toxicants has been responsible to the growing interest in determining the genotoxic effects of xenobiotics to wildlife as a measure of environmental risk. The comet assay, although widely employed in in vivo and in vitro toxicology, still holds many constraints in ERA, in large part owing to difficulties in obtaining conclusive cause-effect relationships from complex environments. Nevertheless, these challenges do not hinder the attempts to apply the alkaline comet assay on sentinel organisms, wild or subjected to bioassays in or ex situ (from fish to molluscs) as well to standardise protocols and establish general guidelines to the interpretation of findings. Fish have been regarded as an appealing subject due to the ease of performing the comet assay in whole blood. However, the application of the comet assay is becoming increasingly common in invertebrates (e.g. in molluscan haemocytes and solid tissues such as gills). Virtually all sorts of results have been obtained from the application of the comet assay in ERA (null, positive and inconclusive). However, it has become clear that interpreting DNA damage data from wild organisms is particularly challenging due to their ability to adapt to continuous environmental stressors, including toxicants. Also, the comet assay in non-model organisms for the purpose of ERA implies different constraints, assumptions and interpretation of findings, compared with the in vitro procedures from which most guidelines have been derived. This paper critically reviews the application of the comet assay in ERA, focusing on target organisms and tissues; protocol developments, case studies plus data handling and

  13. Genotoxic Effects of Low- and High-LET Radiation on Human Epithelial Cells Grown in 2-D Versus 3-D Culture

    Science.gov (United States)

    Patel, Z. S.; Cucinotta, F. A.; Huff, J. L.

    2011-01-01

    Risk estimation for radiation-induced cancer relies heavily on human epidemiology data obtained from terrestrial irradiation incidents from sources such as medical and occupational exposures as well as from the atomic bomb survivors. No such data exists for exposures to the types and doses of high-LET radiation that will be encountered during space travel; therefore, risk assessment for space radiation requires the use of data derived from cell culture and animal models. The use of experimental models that most accurately replicate the response of human tissues is critical for precision in risk projections. This work compares the genotoxic effects of radiation on normal human epithelial cells grown in standard 2-D monolayer culture compared to 3-D organotypic co-culture conditions. These 3-D organotypic models mimic the morphological features, differentiation markers, and growth characteristics of fully-differentiated normal human tissue and are reproducible using defined components. Cultures were irradiated with 2 Gy low-LET gamma rays or varying doses of high-LET particle radiation and genotoxic damage was measured using a modified cytokinesis block micronucleus assay. Our results revealed a 2-fold increase in residual damage in 2 Gy gamma irradiated cells grown under organotypic culture conditions compared to monolayer culture. Irradiation with high-LET particle radiation gave similar results, while background levels of damage were comparable under both scenarios. These observations may be related to the phenomenon of "multicellular resistance" where cancer cells grown as 3-D spheroids or in vivo exhibit an increased resistance to killing by chemotherapeutic agents compared to the same cells grown in 2-D culture. A variety of factors are likely involved in mediating this process, including increased cell-cell communication, microenvironment influences, and changes in cell cycle kinetics that may promote survival of damaged cells in 3-D culture that would

  14. Acute effects of a prooxidant herbicide on the microalga Chlamydomonas reinhardtii: Screening cytotoxicity and genotoxicity endpoints

    International Nuclear Information System (INIS)

    Esperanza, Marta; Cid, Ángeles; Herrero, Concepción; Rioboo, Carmen

    2015-01-01

    Highlights: • Mitochondrial membrane potential constituted the most sensitive parameter assayed. • Several genotoxicity methods were applied for first time in ecotoxicological studies. • Oxidative DNA base damage (8-OHdG) was induced by paraquat exposure. • Cells with DNA strand breakage and subG1-nuclei increased in treated cultures. • Typical apoptosis hallmarks were observed in microalgal cells exposed to paraquat. - Abstract: Since recent evidence has demonstrated that many types of chemicals exhibit oxidative and/or genotoxic potential on living organisms, reactive oxygen species (ROS) formation and DNA damage are currently the best accepted paradigms to assess the potential hazardous biological effects of a wide range of contaminants. The goal of this study was to evaluate the sensitivity of different cytotoxicity and genotoxicity responses on the model microalga Chlamydomonas reinhardtii exposed to the prooxidant herbicide paraquat. In addition to the growth endpoint, cell viability, mitochondrial membrane potential and presence of reactive oxygen species (ROS) were assayed as potential markers of cytotoxicity using flow cytometry (FCM). To study the effects of paraquat on C. reinhardtii DNA, several genotoxicity approaches were implemented for the first time in an ecotoxicological study on microalgae. Oxidative DNA base damage was analysed by measuring the oxidative DNA lesion 8-OHdG by FCM. DNA fragmentation was analysed by different methods: comet assay, and cell cycle analysis by FCM, with a particular focus on the presence of subG1-nuclei. Finally, effects on morphology of nuclei were monitored through DAPI staining. The evaluation of these endpoints showed that several physiological and biochemical parameters reacted to oxidative stress disturbances with greater sensitivity than integrative parameters such as growth rates or cell viability. The experiments revealed concentration-dependent cytotoxicity (ROS formation, depolarization of

  15. Acute effects of a prooxidant herbicide on the microalga Chlamydomonas reinhardtii: Screening cytotoxicity and genotoxicity endpoints

    Energy Technology Data Exchange (ETDEWEB)

    Esperanza, Marta; Cid, Ángeles; Herrero, Concepción; Rioboo, Carmen, E-mail: carmen.rioboo@udc.es

    2015-08-15

    Highlights: • Mitochondrial membrane potential constituted the most sensitive parameter assayed. • Several genotoxicity methods were applied for first time in ecotoxicological studies. • Oxidative DNA base damage (8-OHdG) was induced by paraquat exposure. • Cells with DNA strand breakage and subG1-nuclei increased in treated cultures. • Typical apoptosis hallmarks were observed in microalgal cells exposed to paraquat. - Abstract: Since recent evidence has demonstrated that many types of chemicals exhibit oxidative and/or genotoxic potential on living organisms, reactive oxygen species (ROS) formation and DNA damage are currently the best accepted paradigms to assess the potential hazardous biological effects of a wide range of contaminants. The goal of this study was to evaluate the sensitivity of different cytotoxicity and genotoxicity responses on the model microalga Chlamydomonas reinhardtii exposed to the prooxidant herbicide paraquat. In addition to the growth endpoint, cell viability, mitochondrial membrane potential and presence of reactive oxygen species (ROS) were assayed as potential markers of cytotoxicity using flow cytometry (FCM). To study the effects of paraquat on C. reinhardtii DNA, several genotoxicity approaches were implemented for the first time in an ecotoxicological study on microalgae. Oxidative DNA base damage was analysed by measuring the oxidative DNA lesion 8-OHdG by FCM. DNA fragmentation was analysed by different methods: comet assay, and cell cycle analysis by FCM, with a particular focus on the presence of subG1-nuclei. Finally, effects on morphology of nuclei were monitored through DAPI staining. The evaluation of these endpoints showed that several physiological and biochemical parameters reacted to oxidative stress disturbances with greater sensitivity than integrative parameters such as growth rates or cell viability. The experiments revealed concentration-dependent cytotoxicity (ROS formation, depolarization of

  16. Three-Dimensional, Transgenic Cell Models to Quantify Space Genotoxic Effects

    Science.gov (United States)

    Gonda, S. R.; Sognier, M. A.; Wu, H.; Pingerelli, P. L.; Glickman, B. W.; Dawson, David L. (Technical Monitor)

    1999-01-01

    The space environment contains radiation and chemical agents known to be mutagenic and carcinogenic to humans. Additionally, microgravity is a complicating factor that may modify or synergize induced genotoxic effects. Most in vitro models fail to use human cells (making risk extrapolation to humans more difficult), overlook the dynamic effect of tissue intercellular interactions on genotoxic damage, and lack the sensitivity required to measure low-dose effects. Currently a need exists for a model test system that simulates cellular interactions present in tissue, and can be used to quantify genotoxic damage induced by low levels of radiation and chemicals, and extrapolate assessed risk to humans. A state-of-the-art, three-dimensional, multicellular tissue equivalent cell culture model will be presented. It consists of mammalian cells genetically engineered to contain multiple copies of defined target genes for genotoxic assessment,. NASA-designed bioreactors were used to coculture mammalian cells into spheroids, The cells used were human mammary epithelial cells (H184135) and Stratagene's (Austin, Texas) Big Blue(TM) Rat 2 lambda fibroblasts. The fibroblasts were genetically engineered to contain -a high-density target gene for mutagenesis (60 copies of lacl/LacZ per cell). Tissue equivalent spheroids were routinely produced by inoculation of 2 to 7 X 10(exp 5) fibroblasts with Cytodex 3 beads (150 micrometers in diameter). at a 20:1 cell:bead ratio, into 50-ml HARV bioreactors (Synthecon, Inc.). Fibroblasts were cultured for 5 days, an equivalent number of epithelial cells added, and the fibroblast/epithelial cell coculture continued for 21 days. Three-dimensional spheroids with diameters ranging from 400 to 600 micrometers were obtained. Histological and immunohistochemical Characterization revealed i) both cell types present in the spheroids, with fibroblasts located primarily in the center, surrounded by epithelial cells; ii) synthesis of extracellular matrix

  17. Critical Vidders

    DEFF Research Database (Denmark)

    Svegaard, Robin Sebastian Kaszmarczyk

    2015-01-01

    This article will introduce and take a look at a specific subset of the fan created remix videos known as vids, namely those that deal with feminist based critique of media. Through examples, it will show how fans construct and present their critique, and finally broach the topic of the critical ...

  18. Epigenetic considerations in aquaculture

    Directory of Open Access Journals (Sweden)

    Mackenzie R. Gavery

    2017-12-01

    Full Text Available Epigenetics has attracted considerable attention with respect to its potential value in many areas of agricultural production, particularly under conditions where the environment can be manipulated or natural variation exists. Here we introduce key concepts and definitions of epigenetic mechanisms, including DNA methylation, histone modifications and non-coding RNA, review the current understanding of epigenetics in both fish and shellfish, and propose key areas of aquaculture where epigenetics could be applied. The first key area is environmental manipulation, where the intention is to induce an ‘epigenetic memory’ either within or between generations to produce a desired phenotype. The second key area is epigenetic selection, which, alone or combined with genetic selection, may increase the reliability of producing animals with desired phenotypes. Based on aspects of life history and husbandry practices in aquaculture species, the application of epigenetic knowledge could significantly affect the productivity and sustainability of aquaculture practices. Conversely, clarifying the role of epigenetic mechanisms in aquaculture species may upend traditional assumptions about selection practices. Ultimately, there are still many unanswered questions regarding how epigenetic mechanisms might be leveraged in aquaculture.

  19. Critical reading and critical thinking Critical reading and critical thinking

    Directory of Open Access Journals (Sweden)

    Loni Kreis Taglieber

    2008-04-01

    Full Text Available The purpose of this paper is to provide, for L1 and L2 reading and writing teachers, a brief overview of the literature about critical reading and higher level thinking skills. The teaching of these skills is still neglected in some language classes in Brazil, be it in L1 or in L2 classes. Thus, this paper may also serve as a resource guide for L1 and/or L2 reading and writing teachers who want to incorporate critical reading and thinking into their classes. In modern society, even in everyday life people frequently need to deal with complicated public and political issues, make decisions, and solve problems. In order to do this efficiently and effectively, citizens must be able to evaluate critically what they see, hear, and read. Also, with the huge amount of printed material available in all areas in this age of “information explosion” it is easy to feel overwhelmed. But often the information piled up on people’s desks and in their minds is of no use due to the enormous amount of it. The purpose of this paper is to provide, for L1 and L2 reading and writing teachers, a brief overview of the literature about critical reading and higher level thinking skills. The teaching of these skills is still neglected in some language classes in Brazil, be it in L1 or in L2 classes. Thus, this paper may also serve as a resource guide for L1 and/or L2 reading and writing teachers who want to incorporate critical reading and thinking into their classes. In modern society, even in everyday life people frequently need to deal with complicated public and political issues, make decisions, and solve problems. In order to do this efficiently and effectively, citizens must be able to evaluate critically what they see, hear, and read. Also, with the huge amount of printed material available in all areas in this age of “information explosion” it is easy to feel overwhelmed. But often the information piled up on people’s desks and in their minds is of

  20. Quantitative structure-activity relationships for toxicity and genotoxicity of halogenated aliphatic compounds: wing spot test of Drosophila melanogaster.

    Science.gov (United States)

    Chroust, Karel; Pavlová, Martina; Prokop, Zbynek; Mendel, Jan; Bozková, Katerina; Kubát, Zdenek; Zajícková, Veronika; Damborský, Jiri

    2007-02-01

    Halogenated aliphatic compounds were evaluated for toxic and genotoxic effects in the somatic mutation and recombination test employing Drosophila melanogaster. The tested chemicals included chlorinated, brominated and iodinated; mono-, di- and tri-substituted; saturated and unsaturated alkanes: 1,2-dibromoethane, 1-bromo-2-chloroethane, 1-iodopropane, 2,3-dichloropropene, 3-bromo-1-propene, epibromohydrin, 2-iodobutane, 3-chloro-2-methylpropene, 1,2,3-trichloropropane, 1,2-dichloroethane, 1,2-dichlorobutane, 1-chloro-2-methylpropane, 1,3-dichloropropane, 1,2-dichloropropane, 2-chloroethymethylether, 1-bromo-2-methylpropane and 1-chloropentane. N-methyl-N-nitrosourea served as the positive and distilled water as the negative control. The set of chemicals for the toxicological testing was selected by the use of statistical experiment design. Group of unsaturated aliphatic hydrocarbons were generally more toxic than saturated analogues. The genotoxic effect was observed with 14 compounds in the wing spot test, while 3 substances did not show any genotoxicity by using the wing spot test at 50% lethal concentration. The highest number of wing spots was observed in genotoxicity assay with 1-bromo-2-chloroethane, 1,2-dichloroethane, 1,2-dibromoethane and 1-iodopropane. Nucleophilic superdelocalizability calculated by quantum mechanics appears to be a good parameter for prediction of both toxicity and genotoxicity effects of halogenated aliphatic compounds.

  1. Genotoxic and immunotoxic potential effects of selected psychotropic drugs and antibiotics on blue mussel (Mytilus edulis) hemocytes

    International Nuclear Information System (INIS)

    Lacaze, Emilie; Pédelucq, Julie; Fortier, Marlène; Brousseau, Pauline; Auffret, Michel; Budzinski, Hélène; Fournier, Michel

    2015-01-01

    The potential toxicity of pharmaceuticals towards aquatic invertebrates is still poorly understood and sometimes controversial. This study aims to document the in vitro genotoxicity and immunotoxicity of psychotropic drugs and antibiotics on Mytilus edulis. Mussel hemocytes were exposed to fluoxetine, paroxetine, venlafaxine, carbamazepine, sulfamethoxazole, trimethoprim and erythromycin, at concentrations ranging from μg/L to mg/L. Paroxetine at 1.5 μg/L led to DNA damage while the same concentration of venlafaxine caused immunomodulation. Fluoxetine exposure resulted in genotoxicity, immunotoxicity and cytotoxicity. In the case of antibiotics, trimethoprim was genotoxic at 200 μg/L and immunotoxic at 20 mg/L whereas erythromycin elicited same detrimental effects at higher concentrations. DNA metabolism seems to be a highly sensitive target for psychotropic drugs and antibiotics. Furthermore, these compounds affect the immune system of bivalves, with varying intensity. This attests the relevance of these endpoints to assess the toxic mode of action of pharmaceuticals in the aquatic environment. - Highlights: • Psychotropic drugs and antibiotics affect the immune system of Mytilus edulis. • Genotoxic and immunotoxic endpoints were relevant to assess pharmaceuticals toxicity. • DNA metabolism is a highly sensitive target for pharmaceuticals. • Fluoxetine and paroxetine were the most toxic compounds on mussel hemocytes. - Psychotropic drugs and antibiotics have the potential to cause immune toxicity and genotoxicity on Mytilus edulis hemocytes

  2. Xylo-Oligosaccharides and Inulin Affect Genotoxicity and Bacterial Populations Differently in a Human Colonic Simulator Challenged with Soy Protein

    Science.gov (United States)

    Christophersen, Claus T.; Petersen, Anne; Licht, Tine R.; Conlon, Michael A.

    2013-01-01

    High dietary intakes of some protein sources, including soy protein, can increase colonic DNA damage in animals, whereas some carbohydrates attenuate this. We investigated whether inulin and xylo-oligosaccharides (XOS) could be protective against DNA strand breaks by adding them to a human colonic simulator consisting of a proximal vessel (PV) (pH 5.5) and a distal vessel (DV) (pH 6.8) inoculated with human faeces and media containing soy protein. Genotoxicity of the liquid phase and microbial population changes in the vessels were measured. Soy protein (3%) was fermented with 1% low amylose cornstarch for 10 day followed by soy protein with 1% XOS or 1% inulin for 10 day. Inulin did not alter genotoxicity but XOS significantly reduced PV genotoxicity and increased DV genotoxicity. Inulin and XOS significantly increased butyrate concentration in the DV but not PV. Numbers of the key butyrate-producing bacterium Faecalibacterium prausnitzii were significantly increased in the PV and DV by inulin but significantly decreased by XOS in both vessels. Other bacteria examined were also significantly impacted by the carbohydrate treatments or by the vessel (i.e., pH). There was a significant overall inverse correlation between levels of damage induced by the ferments and levels of sulphate-reducing bacteria, Bacteroides fragilis, and acetate. In conclusion, dietary XOS can potentially modulate the genotoxicity of the colonic environment and specific bacterial groups and short chain fatty acids may mediate this. PMID:24064573

  3. Genotoxic and chemopreventive assessment of Cynara scolymus L. aqueous extract in a human-derived liver cell line.

    Science.gov (United States)

    da Silva, Regiane Pereira; Jacociunas, Laura Vicedo; de Carli, Raíne Fogliati; de Abreu, Bianca Regina Ribas; Lehmann, Mauricio; da Silva, Juliana; Ferraz, Alexandre de Barros Falcão; Dihl, Rafael Rodrigues

    2017-10-01

    Cynara scolymus L., popularly known as artichoke, is consumed as food and used as tea infusions for pharmacological purposes to treat liver dysfunctions and other conditions. Scientific data on the safety and protective effect of artichoke in human-derived liver cells is missing. This study investigated the genotoxic and modulatory effect of a liophilized extract suspended in water of C. scolymus L. leaves. Four extract concentrations (0.62, 1.25, 2.5 and 5.0 mg/mL) were evaluated using the comet assay on human hepatocyte cultures, HepG2 cells. Genotoxicity was assessed after two treatment periods, 1 and 24 h. Antigenotoxicity was evaluated against oxidative lesions induced by hydrogen peroxide in pre-, simultaneous and post-treatment protocols. Artichoke leaves aqueous extract induced genotoxic effects in HepG2 cells after 1- and 24-h treatments. In turn, extract concentrations of 0.62, 1.25 and 2.5 mg/mL, exhibited a protective effect in pretreatment, compared to hydrogen peroxide alone. However, in simultaneous and post-treatment protocols, only the lowest concentration reduced the frequency of DNA damage induced by hydrogen peroxide. In addition, in the simultaneous treatment protocol, the highest artichoke extract concentration increased hydrogen peroxide genotoxicity. It can be concluded that artichoke is genotoxic, in vitro, to HepG2 cells, but can also modulate hydrogen peroxide DNA damage.

  4. Integrated analysis of the ecotoxicological and genotoxic effects of the antimicrobial peptide melittin on Daphnia magna and Pseudokirchneriella subcapitata

    International Nuclear Information System (INIS)

    Galdiero, Emilia; Maselli, Valeria; Falanga, Annarita; Gesuele, Renato; Galdiero, Stefania; Fulgione, Domenico; Guida, Marco

    2015-01-01

    Melittin is a major constituent of the bee venom of Apis mellifera with a broad spectrum of activities. Melittin therapeutical potential is subject to its toxicity and the assessment of ecotoxicity and genotoxicity is of particular interest for therapeutic use. Here we analyzed the biological effects of melittin on two aquatic species, which are representative of two different levels of the aquatic trophic chain: the invertebrate Daphnia magna and the unicellular microalgae Pseudokirchneriella subcapitata. The attention was focused on the determination of: i) ecotoxicity; ii) genotoxicity; iii) antigenotoxicity. Our main finding is that melittin is detrimental to D. magna reproduction and its sub-lethal concentrations create an accumulation dependent on exposition times and a negative effect on DNA. We also observed that melittin significantly delayed time to first eggs. Moreover, results showed that melittin exerted its toxic and genotoxic effects in both species, being a bit more aggressive towards P. subcapitata. - Highlights: • We examine ecotoxicity to study how AMPs affect the environment. • We examine genotoxicity in order to analyze the damages to the DNA. • We examine the antigenotoxicity in order to verify DNA repair ability of the cells. • Possible therapeutical applications of AMPs depend on assessment of ecotoxicity. - Melittin exerts its dose dependent toxic and genotoxic effects on both indicators; no toxicity is found at concentrations that may typically reach the environment

  5. Evaluation of genotoxic potential of neurotoxin anatoxin-a with the use of umuC test.

    Science.gov (United States)

    Sieroslawska, Anna; Rymuszka, Anna

    2010-01-01

    The aim of this study was to evaluate genotoxicity of anatoxin-a, cyanotoxin of neurotoxic activity. Additionally, other frequently detected cyanotoxin of previously described genotoxic potential, microcystin-LR, was used at the same concentrations, as well as the mixture of both toxins, anatoxin-a and microcystin-LR. Genotoxicity of the toxins was determined with the use of the umuC assay, in which the induction and expression of the umuC - lacZ reporter gene was assessed. The test was conducted on Salmonella typhimurium TA 1535/pSK1002 strain, with and without metabolic transformation. The toxin concentrations were 0.25, 0.5, 1 and 2 µg/ml. The exposure time was 2 h. The highest inefficient concentration of anatoxin-a without metabolic transformation was 0.25 µg/ml, of microcystin-LR was 0.5 µg/ml and in case of the toxin mixture all used concentrations induced the umuC gene. When S9 fraction was added to the samples, no effects were detected. To our knowledge, this is the first report on genotoxic effects of anatoxin-a. Although the study is preliminary and needs further research, however, indicates the new potential activity of the toxin, as well as the possible increase of genotoxicity of other cyanotoxins, more stable in the environment, e.g. microcystin-LR.

  6. Criticality accident:

    International Nuclear Information System (INIS)

    Canavese, Susana I.

    2000-01-01

    A criticality accident occurred at 10:35 on September 30, 1999. It occurred in a precipitation tank in a Conversion Test Building at the JCO Tokai Works site in Tokaimura (Tokai Village) in the Ibaraki Prefecture of Japan. STA provisionally rated this accident a 4 on the seven-level, logarithmic International Nuclear Event Scale (INES). The September 30, 1999 criticality accident at the JCO Tokai Works Site in Tokaimura, Japan in described in preliminary, technical detail. Information is based on preliminary presentations to technical groups by Japanese scientists and spokespersons, translations by technical and non-technical persons of technical web postings by various nuclear authorities, and English-language non-technical reports from various news media and nuclear-interest groups. (author)

  7. Critical dynamics

    International Nuclear Information System (INIS)

    Dekker, H.

    1980-01-01

    It is shown how to solve the master equation for a Markov process including a critical point by means of successive approximations in terms of a small parameter. A critical point occurs if, by adjusting an externally controlled quantity, the system shows a transition from normal monostable to bistable behaviour. The fundamental idea of the theory is to separate the master equation into its proper irreducible part and a corrective remainder. The irreducible or zeroth order stochastic approximation will be a relatively simple Fokker-Planck equation that contains the essential features of the process. Once the solution of this irreducible equation is known, the higher order corrections in the original master equation can be incorporated in a systematic manner. (Auth.)

  8. Marxist Criticism of (Unsustainable Development

    Directory of Open Access Journals (Sweden)

    Rosana de Carvalho Martinelli Freitas

    2012-06-01

    approaches that are critical of the concept of sustainable development, which, although commonly used, is ambiguous and the motive of considerable controversy. Finally, factors are present for a new approach to environmental issues considering the unsustainability inherent to the capitalist mode of production and the destruction that accompanies it.

  9. Critical scattering

    International Nuclear Information System (INIS)

    Stirling, W.G.; Perry, S.C.

    1996-01-01

    We outline the theoretical and experimental background to neutron scattering studies of critical phenomena at magnetic and structural phase transitions. The displacive phase transition of SrTiO 3 is discussed, along with examples from recent work on magnetic materials from the rare-earth (Ho, Dy) and actinide (NpAs, NpSb, USb) classes. The impact of synchrotron X-ray scattering is discussed in conclusion. (author) 13 figs., 18 refs

  10. Clinical trial considerations on male contraception and collection of pregnancy information from female partners

    Directory of Open Access Journals (Sweden)

    Banholzer Maria

    2012-06-01

    Full Text Available Abstract Background There is little guidance regarding the risk of exposure of pregnant women/ women of childbearing potential to genotoxic or teratogenic compounds via vaginal dose delivered through seminal fluid during sexual intercourse. Method We summarize current thinking and provide clinical trial considerations for a consistent approach to contraception for males exposed to genotoxic and/or teratogenic compounds or to compounds of unknown teratogenicity, and for collection of pregnancy data from their female partners. Results Where toxicity testing demonstrates genotoxic potential, condom use is required during exposure and for 5 terminal plasma half-lives plus 74 days (one human spermatogenesis cycle to avoid conception. For non-genotoxic small molecules and immunoglobulins with unknown teratogenic potential or without a no observed adverse effect level (NOAEL from embryo-fetal development (EFD studies and no minimal anticipated biological effect level (MABEL, condom use is recommended for males with pregnant partner/female partner of childbearing potential. For teratogenic small molecules with estimated seminal fluid concentration and a margin between projected maternal area under the curve (AUC and NOAEL AUC from EFD studies of ≥300 (≥100 for immunoglobulins or in the absence of a NOAEL with a margin between MABEL plasma concentration and maternal Cmax of ≥300 (≥10 for immunoglobulins, condom use is not required. However, condom use is required for margins below the thresholds previously indicated. For small molecules with available seminal fluid concentrations, condom use is required if margins are Pregnancy data should be proactively collected if pregnancy occurs during the condom use period required for males exposed to first-in-class molecules or to molecules with a target/class shown to be teratogenic, embryotoxic or fetotoxic in human or preclinical experiments. Conclusion These recommendations, based on a precaution

  11. Ebola: translational science considerations.

    Science.gov (United States)

    Chiappelli, Francesco; Bakhordarian, Andre; Thames, April D; Du, Angela M; Jan, Allison L; Nahcivan, Melissa; Nguyen, Mia T; Sama, Nateli; Manfrini, Ercolano; Piva, Francesco; Rocha, Rafael Malagoli; Maida, Carl A

    2015-01-16

    We are currently in the midst of the most aggressive and fulminating outbreak of Ebola-related disease, commonly referred to as "Ebola", ever recorded. In less than a year, the Ebola virus (EBOV, Zaire ebolavirus species) has infected over 10,000 people, indiscriminately of gender or age, with a fatality rate of about 50%. Whereas at its onset this Ebola outbreak was limited to three countries in West Africa (Guinea, where it was first reported in late March 2014, Liberia, where it has been most rampant in its capital city, Monrovia and other metropolitan cities, and Sierra Leone), cases were later reported in Nigeria, Mali and Senegal, as well as in Western Europe (i.e., Madrid, Spain) and the US (i.e., Dallas, Texas; New York City) by late October 2014. World and US health agencies declared that the current Ebola virus disease (EVD) outbreak has a strong likelihood of growing exponentially across the world before an effective vaccine, treatment or cure can be developed, tested, validated and distributed widely. In the meantime, the spread of the disease may rapidly evolve from an epidemics to a full-blown pandemic. The scientific and healthcare communities actively research and define an emerging kaleidoscope of knowledge about critical translational research parameters, including the virology of EBOV, the molecular biomarkers of the pathological manifestations of EVD, putative central nervous system involvement in EVD, and the cellular immune surveillance to EBOV, patient-centered anthropological and societal parameters of EVD, as well as translational effectiveness about novel putative patient-targeted vaccine and pharmaceutical interventions, which hold strong promise, if not hope, to curb this and future Ebola outbreaks. This work reviews and discusses the principal known facts about EBOV and EVD, and certain among the most interesting ongoing or future avenues of research in the field, including vaccination programs for the wild animal vectors of the virus

  12. Co-formation and co-release of genotoxic PAHs, alkyl-PAHs and soot nanoparticles from gasoline direct injection vehicles

    Science.gov (United States)

    Muñoz, Maria; Haag, Regula; Honegger, Peter; Zeyer, Kerstin; Mohn, Joachim; Comte, Pierre; Czerwinski, Jan; Heeb, Norbert V.

    2018-04-01

    Gasoline direct injection (GDI) vehicles quickly replace traditional port-fuel injection (PFI) vehicles in Europe reaching about 50 million vehicles on roads in 2020. GDI vehicles release large numbers of soot nanoparticles similar to conventional diesel vehicles without particle filters. These exhausts will increasingly affect air quality in European cities. We hypothesized that such particles are released together with polycyclic aromatic hydrocarbons (PAHs) formed under the same combustion conditions. Emission data of a fleet of 7 GDI vehicles (1.2-1.8 L) including Euro-3,-4,-5 and -6 technologies revealed substantial particle emissions on average of 2.5 × 1012 particles km-1 in the cold worldwide harmonized light vehicle test cycle (cWLTC), the future European legislative driving cycle. Particle emissions increased 2-3 orders of magnitude during acceleration like CO, indicating that transient driving produces fuel-rich conditions with intense particle formation. For comparison, an Euro-5 diesel vehicle (1.6 L) equipped with a particle filter released 3.9 × 1010 particles km-1 (cWLTC), clearly within the Euro-5/6 limit value of 6.0 × 1011 particles km-1 and 64-fold below the GDI fleet average. PAH and alkyl-PAH emissions of the GDI vehicles also exceeded those of the diesel vehicle. Mean GDI emissions of 2-, 3-, 4-, 5- and 6-ring PAHs in the cWLTC were 240, 44, 5.8, 0.5 and 0.4 μg km-1, those of the diesel vehicle were only 8.8, 7.1, 8.6, 0.02 and 0.02 μg km-1, respectively. Thus mean PAH emissions of the GDI fleet were 2 orders of magnitude higher than the bench mark diesel vehicle. A comparison of the toxicity equivalent concentrations (TEQ) in the cWLTC of the GDI fleet and the diesel vehicle revealed that GDI vehicles released 200-1700 ng TEQ m-3 genotoxic PAHs, being 6-40 times higher than the diesel vehicle with 45 ng TEQ km-1. The co-release of genotoxic PAHs adsorbed on numerous soot nanoparticles is critical due to the Trojan horse effect

  13. Assessment of the in vitro and in vivo genotoxicity of extracts and indole monoterpene alkaloid from the roots of Galianthe thalictroides (Rubiaceae).

    Science.gov (United States)

    Fernandes, L M; Garcez, W S; Mantovani, M S; Figueiredo, P O; Fernandes, C A; Garcez, F R; Guterres, Z R

    2013-09-01

    Roots of Galianthe thalictroides K. Schum. (Rubiaceae) are used in folk medicine in the State of Mato Grosso do Sul, Brazil, for treating and preventing cancer. To gain information about the genotoxicity of extracts (aqueous and EtOH), the CHCl₃ phase resulting from partition of the EtOH extract and the indole monoterpene alkaloid 1 obtained from this plant. The genotoxicity of 1 and extracts was evaluated in vivo through the Drosophila melanogaster wing Somatic Mutation and Recombination Test - SMART, while in vitro cytotoxic (MTT) and Comet assays were performed only with alkaloid 1. The results obtained with the SMART test indicated that the aqueous extract had no genotoxic activity. The EtOH extract was not genotoxic to ST descendants but genotoxic to HB ones. The CHCl₃ phase was genotoxic and cytotoxic. Alkaloid 1 showed significant mutational events with SMART, in the cytotoxicity assay (MTT), it showed a high cytotoxicity for human hepatoma cells (HepG2), whereas for the Comet assay, not showing genotoxic activity. The ethanol extract was shown to be genotoxic to HB descendants in the SMART assay, while the results obtained in this test for the monoterpene indole alkaloid 1 isolated from this extract. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Development of a Fish Cell Biosensor System for Genotoxicity Detection Based on DNA Damage-Induced Trans-Activation of p21 Gene Expression

    Directory of Open Access Journals (Sweden)

    Huarong Guo

    2012-09-01

    Full Text Available p21CIP1/WAF1 is a p53-target gene in response to cellular DNA damage. Here we report the development of a fish cell biosensor system for high throughput genotoxicity detection of new drugs, by stably integrating two reporter plasmids of pGL3-p21-luc (human p21 promoter linked to firefly luciferase and pRL-CMV-luc (CMV promoter linked to Renilla luciferase into marine flatfish flounder gill (FG cells, referred to as p21FGLuc. Initial validation of this genotoxicity biosensor system showed that p21FGLuc cells had a wild-type p53 signaling pathway and responded positively to the challenge of both directly acting genotoxic agents (bleomycin and mitomycin C and indirectly acting genotoxic agents (cyclophosphamide with metabolic activation, but negatively to cyclophosphamide without metabolic activation and the non-genotoxic agents ethanol and D-mannitol, thus confirming a high specificity and sensitivity, fast and stable response to genotoxic agents for this easily maintained fish cell biosensor system. This system was especially useful in the genotoxicity detection of Di(2-ethylhexyl phthalate (DEHP, a rodent carcinogen, but negatively reported in most non-mammalian in vitro mutation assays, by providing a strong indication of genotoxicity for DEHP. A limitation for this biosensor system was that it might give false positive results in response to sodium butyrate and any other agents, which can trans-activate the p21 gene in a p53-independent manner.

  15. The cda GenoTox assay: A new and sensitive method for detection of environmental genotoxins, including nitroarenes and aromatic amines

    DEFF Research Database (Denmark)

    Østergaard, Trine G.; Hansen, Lars Henrik; Binderup, Mona-Lise

    2007-01-01

    A new bacterial test system for detection of genotoxic compounds was developed, based on two new Sahnonella typhimurium tester strains, TGO1 and TGO2. Both strains contain a gene fusion between a strong SOS-promotor, P-cda, and the gfp gene, which allows detection of genotoxic compounds that indu...

  16. Ecotoxicity and genotoxicity of cyclophosphamide, ifosfamide, their metabolites/transformation products and their mixtures

    International Nuclear Information System (INIS)

    Česen, Marjeta; Eleršek, Tina; Novak, Matjaž; Žegura, Bojana; Kosjek, Tina; Filipič, Metka; Heath, Ester

    2016-01-01

    Cyclophosphamide (CP) and ifosfamide (IF) are commonly used cytostatic drugs that repress cell division by interaction with DNA. The present study investigates the ecotoxicity and genotoxicity of CP, IF, their human metabolites/transformation products (TPs) carboxy-cyclophosphamide (CPCOOH), keto-cyclophosphamide (ketoCP) and N-dechloroethyl-cyclophosphamide (NdCP) as individual compounds and as mixture. The two parent compounds (CP and IF), at concentrations up to 320 mg L −1 , were non-toxic towards the alga Pseudokirchneriella subcapitata and cyanobacterium Synecococcus leopoliensis. Further ecotoxicity studies of metabolites/TPs and a mixture of parent compounds and metabolites/TPs performed in cyanobacteria S. leopoliensis, showed that only CPCOOH (EC 50  = 17.1 mg L −1 ) was toxic. The measured toxicity (EC 50  = 11.5 mg L −1 ) of the mixture was lower from the toxicity predicted by concentration addition model (EC 50  = 21.1 mg L −1 ) indicating potentiating effects of the CPCOOH toxicity. The SOS/umuC assay with Salmonella typhimurium revealed genotoxic activity of CP, CPCOOH and the mixture in the presence of S9 metabolic activation. Only CPCOOH was genotoxic also in the absence of metabolic activation indicating that this compound is a direct acting genotoxin. This finding is of particular importance as in the environment such compounds can directly affect DNA of non-target organisms and also explains toxicity of CPCOOH against cyanobacteria S. leopoliensis. The degradation study with UV irradiation of samples containing CP and IF showed efficient degradation of both compounds and remained non-toxic towards S. leopoliensis, suggesting that no stable TPs with adverse effects were formed. To our knowledge, this is the first study describing the ecotoxicity and genotoxicity of the commonly used cytostatics CP and IF, their known metabolites/TPs and their mixture. The results indicate the importance of toxicological evaluation and

  17. A diet high in fat and meat but low in dietary fibre increases the genotoxic potential of 'faecal water'

    DEFF Research Database (Denmark)

    Rieger, Martin A.; Parlesak, Alexandr; Pool-Zobel, Beatrice

    1999-01-01

    To determine the effects of different diets on the genotoxicity of human faecal water, a diet rich in fat, meat and sugar but poor in vegetables and free of wholemeal products (diet 1) was consumed by seven healthy volunteers over a period of 12 days. One week after the end of this period......, the volunteers started to consume a diet enriched with vegetables and wholemeal products but poor in fat and meat (diet 2) over a second period of 12 days. The genotoxic effect of faecal waters obtained after both diets was assessed with the single cell gel electrophoresis (Comet assay) using the human colon...... and purine bases revealed no differences after pretreatment with both types of faecal water. The results indicate that diets high in fat and meat but low in dietary fibre increase the genotoxicity of faecal water to colonic cells and may contribute to an enhanced risk of colorectal cancer....

  18. DNA-synthesis inhibition and repair DNA-synthesis in CHO Ade- C cells: An alternative approach to genotoxicity testing

    International Nuclear Information System (INIS)

    Slamenova, D.; Papsova, E.; Gabelova, A.; Dusinska, M.; Collins, A.; Wsolova, L.

    1997-01-01

    We describe an alternative assay to determine genotoxicity. Its main feature is that it combines two measures in a single experiment; the inhibition of replicative DNA synthesis together with the stimulation of DNA repair. We show that, in tests of four different genotoxic agents, the assay gives results that are entirely consistent with what is known about the mode of action of these agents. In addition, we have demonstrated that chemical carcinogens requiring metabolic activation can be examined using a standard procedure of incubation with a microsomal activating fraction. We consider the combined assay for DNA synthesis inhibition and repair synthesis to be a useful way for the rapid pre-screening of chemicals suspected of genotoxic activity on the level of mammalian cells. (author)

  19. Xylo-oligosaccharides and inulin affect genotoxicity and bacterial populations differently in a human colonic simulator challenged with soy protein

    DEFF Research Database (Denmark)

    Christophersen, C. T.; Petersen, Anne; Licht, Tine Rask

    2013-01-01

    High dietary intakes of some protein sources, including soy protein, can increase colonic DNA damage in animals, whereas some carbohydrates attenuate this. We investigated whether inulin and xylo-oligosaccharides (XOS) could be protective against DNA strand breaks by adding them to a human colonic...... cornstarch for 10 day followed by soy protein with 1% XOS or 1% inulin for 10 day. Inulin did not alter genotoxicity but XOS significantly reduced PV genotoxicity and increased DV genotoxicity. Inulin and XOS significantly increased butyrate concentration in the DV but not PV. Numbers of the key butyrate......-producing bacterium Faecalibacterium prausnitzii were significantly increased in the PV and DV by inulin but significantly decreased by XOS in both vessels. Other bacteria examined were also significantly impacted by the carbohydrate treatments or by the vessel (i.e., pH). There was a significant overall inverse...

  20. Randomly amplified polymorphic-DNA analysis for detecting genotoxic effects of Boron on maize (Zea mays L.).

    Science.gov (United States)

    Sakcali, M Serdal; Kekec, Guzin; Uzonur, Irem; Alpsoy, Lokman; Tombuloglu, Huseyin

    2015-08-01

    This study was carried out to investigate the genotoxic effect of boron (B) on maize using randomly amplified polymorphic DNA (RAPD) method. Experimental design was conducted under 0, 5, 10, 25, 50, 100, 125, and 150 ppm B exposures, and physiological changes have revealed a sharp decrease in root growth rates from 28% to 85%, starting from 25 ppm to 150 ppm, respectively. RAPD-polymerase chain reaction (PCR) analysis shows that DNA alterations are clearly observed from beginning to 100 ppm. B-induced inhibition in root growth had a positive correlation with DNA alterations. Total soluble protein, root and stem lengths, and B content analysis in root and leaves encourage these results as a consequence. These preliminary findings reveal that B causes chromosomal aberration and genotoxic effects on maize. Meanwhile, usage of RAPD-PCR technique is a suitable biomarker to detect genotoxic effect of B on maize and other crops for the future. © The Author(s) 2013.