Search results for: genotoxicity-and-dna-repair

Genotoxicity and DNA Repair

Author : L. María Sierra
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Genotoxicity and DNA Repair: A Practical Approach provides a key reference for determining how to analyze the genotoxic activity of molecules or materials and, at the same time, serves as a useful tool for researchers in the Environmental Mutagenesis and DNA Repair fields. Focused on genotoxicity assays recommended by the “OECD guidelines for the testing of chemicals”, this volume also covers other useful assays, such as some gene mutation assays, the comet assay in different species and applications, and the SMART assays of Drosophila. For all the assays, the book presents brief theoretical introductions to the topics and updated standard and modified step-by-step protocols to perform them. Special emphasis is placed on the analysis of nanoparticles, including an integrative approach analysis. The DNA Repair section includes several assays that provide information on repair activity in vitro and in vivo, as well as recent applications to study DNA repair in humans, cell cultures, and animal models. As a volume in the Methods in Pharmacology and Toxicology series, the chapters contain the kind of detail and key implementation advice that ensures reproducible results in the lab. Authoritative and invaluable, Genotoxicity and DNA Repair: A Practical Approach aims to aid scientists in their pursuit of forwarding this vital field of study.

Relating Genotoxicity to DNA Repair and Reproductive Success in Zebrafish Danio Rerio Exposed to Environmental Toxicants

Author : Helena C. Reinardy
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Comparative Cytotoxicity Genotoxicity and DNA Repair Kinetics of Drinking Water Disinfection By products

Author : Justin A. Pals
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30 years of the Comet Assay an overview with some new insights

Author : Amaya Azqueta
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By means of this ‘Frontiers in Genetics’ research topic, we are celebrating 30 years of the Comet Assay. The first paper on this single-cell gel electrophoresis assay was published in 1984 by O. Ostling and K.J. Johanson (Biochem. Biophys. Res. Commun. Vol.123: 291-298). The comet assay is a versatile and sensitive method for measuring single - and double-strand breaks in DNA. By including lesion-specific enzymes in the assay, its range and sensitivity are greatly increased, but it is important to bear in mind that their specificity is not absolute. The comet assay (with and without inclusion of lesion-specific enzymes) is widely used as a biomarker assay in human population studies - primarily to measure DNA damage, but increasingly also to assess the capacity of cells for DNA repair. Ostling and Johanson (Biochem. Biophys. Res. Commun., 1984) were also the first to report experiments to measure DNA repair, by simply following the decrease of DNA damage over time after challenging cells with ionising radiation. However, this approach is time-consuming and laborious as it requires an extended period of cell culture and is therefore not ideal for biomonitoring studies, which typically require high-throughput processing of many samples. As an alternative approach, the in vitro comet-based repair assay was developed: a cell extract is incubated with a DNA substrate containing specific lesions, and DNA incisions accumulate. The in vitro comet-based repair assay has been modified and improved over the past decade: it was first devised to measure base excision repair of oxidised purines in lymphocytes (Collins et al., Mutagenesis, 2001), but has since been adapted for other lesions and thus other repair pathways, as well as being applied to tissue samples in addition to cell suspensions. Even after 30 years, the comet assay is still in a growth phase, with many new users each year. Many questions are repeatedly raised, which may seem to have self-evident answers, but clearly, it is necessary to reiterate them for the benefit of the new audience, and sometimes being forced to think again about old topics can shed new light. Different applications of the comet assay are discussed in this special issue, including: genotoxicity testing in different organisms, human biomonitoring, DNA repair studies, environmental biomonitoring and clinical studies. Furthermore, we consider and where possible answer questions, including the ones raised by Raymond Tice at the 8th International Comet Assay Workshop in Perugia (Italy 2009): What is the spectrum of DNA damage detected by the various versions of the comet assay?; What are the limitations associated with each application?; What should be done to standardize the assay for biomonitoring studies?; Can the comet assay be used to monitor changes in global methylation status?; What cell types are suitable for detecting genotoxic substances and their effects in vivo and in vitro?; Can the assay be fully automated?; and more. So this ‘Frontiers in Genetics’ research topic is written for the beginner as well as for the experienced users of the comet assay.

The Cellular Response to the Genotoxic Insult

Author : Helmut Greim
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Genotoxic carcinogens can lead to DNA mutations with the potential to cause cancer. Typically, a series of mutation events are needed before malignancy occurs so a single, small exposure may not result in disease. Also, cells have an armoury of defence mechanisms which, to a degree, counter the effects of mutagens. Distinguishing the point at which exposure to a carcinogen increases mutation rates beyond the background level is challenging. In fact, there is now general agreement that, for genotoxic carcinogens, no specific threshold can be identified. However, NOAELs (No Observed Adverse Effect Levels) may be used in the process of establishing a dose-response relationship. These denote the level of exposure at which there is no significant increase in adverse effects in the exposed population when compared to an appropriate control. Such a scientifically defendable threshold allows us to propose health based exposure limits for genotoxic carcinogens. This book describes the various cellular defence mechanisms individually and explains how they are regulated. The processes covered include metabolic inactivation, epigenetic regulation, scavenging mechanisms, DNA-repair and apoptosis. It also considers dose-dependent threshold mechanisms of carcinogenesis and the rate limiting parameters. Aimed at graduate level and above, the book discusses the consequences of genotoxic evaluation and urges readers to question the idea that even low exposures present a cancer risk.

Environmental Metal Pollutants Reactive Oxygen Intermediaries and Genotoxicity

Author : Maria E. Ariza
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Humans are exposed daily to low concentrations of metals that are released into the environment by both natural and industrial processes. Environmental Metal Pollutants, Reactive Oxygen Intermediaries and Genotoxicity: Molecular Approaches to Determine Mechanisms of Toxicity examines concerns about the acute and/or chronic exposure of humans to concentrations of these metals that are below the threshold levels established by various federal regulatory agencies. Some of these metals are accumulated in various tissues and over time this may result in the accumulation of a significant body burden. This could increase the risk of developing a variety of diseases later in life, at a time when thresholds for such effects may already be reduced by the processes of aging. Such possibilities could only further compromise the quality of life in the elderly population and could contribute to the rising cost of health care in this country. Studies that have been conducted to determine the possible risks associated with exposure to relatively non-toxic concentrations of environmental metals have been hampered by a lack of appropriate models and a lack of funding. It has also been difficult for researchers to demonstrate a correlation between the exposure of humans or animals to low concentrations of environmental pollutants and disease. This book examines recent technological advances in the areas of molecular biology, biochemistry, and computer-enhanced image analyses that provide researchers with the tools to begin elucidating the genotoxic effects of environmental metal pollutants and the mechanisms by which these metals cause DNA damage. Environmental Metal Pollutants, Reactive Oxygen Intermediaries and Genotoxicity: Molecular Approaches to Determine Mechanisms of Toxicity presents data that demonstrate that certain environmental metal pollutants are genotoxic. The authors describe the role of reactive oxygen intermediates in causing the DNA damage induced by environmental metal pollutants and discuss their possible role in human disease.

Paraquat Genotoxicity in Mammalian Cells

Author : Sandra J. Gunselman
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The Comet Assay in Toxicology

Author : Alok Dhawan
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Concerns about the adverse effects of chemicals present in the environment have created a need for better systems to assess their potential consequences on human health. One potential solution is the versatile and state-of-the-art Comet assay. Simple, sensitive, rapid and visual, this modern toxicological method allows quantitative and qualitative assessment of DNA damage in single cells. This unique reference is devoted exclusively to the Comet assay and addresses, in-depth, the different protocols, statistical analyses and applications being used worldwide. It also includes the guidelines recommended by the working group on Comet assay. The book is aimed at students as well as scientists in the area of molecular epidemiology and genetic toxicology.

Genotoxicity and Mutagenicity

Author : Sonia Soloneski
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An Investigation of Genotoxicity and Antioxidant Treatment of DNA Repair in Human Cells

Author : Pratibha Mistry
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Insight on Genotoxicity

Author : Shiv Shankar Shukla
File Size : 70.99 MB
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Genetic toxicology is considered to be an important assessment tool as there is genetic impact of artificial chemicals. Insight on Genotoxicity discusses testing, mechanism, prediction, and bioindicator of genotoxicity taking into consideration recent advances in nano-engineered particles. Corollary of DNA dent is also discussed in detail taking into consideration the impact of ICH guidelines on genotoxicity testing, which is important for drug discovery innovation and development. Perspective review of genotoxicity evaluation in phytopharmaceuticals has been mentioned along with the prevention of genotoxicity in brief viewpoint. Salient Features Presents methods, standard protocols, and guidelines for genotoxicity testing Examines the impact of ICH Guidelines on genetic toxicity testing which is a regulatory requirement for drug discovery and development Defines appropriate strategies about advances in in vivo genotoxicity testing which have been listed along with progress and prospects Discusses advancement in the high-throughput approaches for genotoxicity testing Details computational prediction of genotoxicity with consideration of mutagenicity, chromosomal damage caused and strategies for computational prediction in drug development

Mechanisms of Genome Protection and Repair

Author : Dmitry O. Zharkov
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DNA is under constant challenge from environmental and endogenous metabolic assaults. Several layers of defence and repair systems allow cells to maintain stable genomes; in humans, dysfunction of these systems leads to cancer, neurodegeneration, and other pathologies. At the same time, recently it had emerged that targeted and regulated DNA damage and repair is a mechanism underlying several important cellular processes such as epigenetic demethylation and immunoglobulin gene diversification. The present collection of papers is aimed to cover new developments in the area of protective and regulatory mechanisms associated with DNA damage. The mechanisms ruling the recognition of damaged nucleotides against the vast background of normal ones are reviewed. The role of extended non-catalytic domains that are often found in eukaryotic DNA repair proteins in contrast to their downsized, catalytic-only bacterial counterparts is discussed. Among the proposed subjects are the regulatory functions of bulky covalent modifications such as poly(ADP)ribosylation and ubiquitylation in DNA damage response, especially in the context of chromatin remodelling. As opposed to DNA repair, damage tolerance allows cells to replicate with lesions in the genome; the enzymes responsible are also covered. Finally, we present examples of modern multilevel understanding of the cell function and malfunction in the wake of genotoxic assaults such as oxidative stress, abiotic environmental stress, and DNA-damaging plant toxins.

Cytotoxicity and Genotoxicity of Urban Particulate Matter in DNA Repair Proficient and Deficient Mammalian Cells

Author : Audrey Dumax-Vorzet
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Air pollution (especially airborne particulate matter (PM)) can have serious effects on human health. PM exposure can increase cardiovascular and pulmonary complaints and lung cancer. These health effects reflect alterations in cellular function possibly due to damage in DNA caused by PM. A number of specialised pathways exist in mammalian cells to repair and I or by-pass different types of DNA damage. Base excision repair deals with oxidative DNA lesions which are recognised by Oggl, Nthl and Neill DNA glycosylases. The aim of this study is to investigate the role of different DNA repair proteins (including DNA glycosylases) in the protection of cellular DNA against PM-induced damage. To do so, the expression level of the proteins of interest was reduced in mouse cells and the level of cell death and DNA damage in these cells was studied and compared with unmodified I control cells. The oxidative capacity of PM was investigated to try and understand the mechanism involved in cellular toxicity. Different PM samples were used in this study: PM collected in. Manchester during the summer and winter, diesel exhaust dust from a race car engine and standard urban dust from NIST. All the PM samples could catalyse the production of oxygen radicals in the absence of cells, but DEP only could generate oxygen radicals inside cells. All the PM samples caused cell death and DNA damage, but to a different extent. Urban dust caused more cells death and DNA damage than the other PM samples. Nthl and Oggl protect mammalian cells against PM-induced cell death while Neill did not have any effect. DNA polymerase K may also have a small role in the preservation of cell viability following PM exposure. Urban dust and DEP caused a higher level of DNA damage in Nthl and Oggl deficient cells than in control cells. Neill deficiency decreased the level of DNA damage following DEP exposure compared to control cells. This study showed that DNA glycosylases are important for the protection of mouse cells against PM-induced DNA damage and cell death. These results indicate that the activity of DNA repair proteins may help predict individual sensitivity to PM- induced health effects in exposed subjects.

Mechanisms of DNA Damage and Repair

Author : Michael G. Simic
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This book is based on the papers presented at the conference on "Mecha nisms of DNA Damage and Repair: Implications for Carcinogenesis and Risk Assessment," held at the National Bureau of Standards on June 2-7, 1985, This volume deals with mechanisms of DNA damage and repair at the molecular level; consequences of unrepaired or misrepaired damage, with major emphasis on carcinogenesis; drugs which bind selectively to altered and potentially damaging DNA sequences; and potential utilization of DNA damage as an endpoint for assessing risks of UV light, ionizing radiations, chemicals, drugs, and hazardous agents in foods. Because the induction of mutations by radiation and genotoxic chemicals has been observed to follow one-hit kinetics in some instances, it is generally assumed that any level of exposure to a DNA-damaging agent may increase the risk of genetic disease or cancer in an exposed population. At the same time, however, there is evidence that although the DNA of living cells is continually damaged by natural background radiation, free radicals, and other naturally occurring processes, most of the damage is normally repaired.

Mechanisms of Genome Protection and Repair

Author : Dmitry O. Zharkov
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DNA is under constant challenge from environmental and endogenous metabolic assaults. Several layers of defence and repair systems allow cells to maintain stable genomes; in humans, dysfunction of these systems leads to cancer, neurodegeneration, and other pathologies. At the same time, recently it had emerged that targeted and regulated DNA damage and repair is a mechanism underlying several important cellular processes such as epigenetic demethylation and immunoglobulin gene diversification. The present collection of papers is aimed to cover new developments in the area of protective and regulatory mechanisms associated with DNA damage. The mechanisms ruling the recognition of damaged nucleotides against the vast background of normal ones are reviewed. The role of extended non-catalytic domains that are often found in eukaryotic DNA repair proteins in contrast to their downsized, catalytic-only bacterial counterparts is discussed. Among the proposed subjects are the regulatory functions of bulky covalent modifications such as poly(ADP)ribosylation and ubiquitylation in DNA damage response, especially in the context of chromatin remodelling. As opposed to DNA repair, damage tolerance allows cells to replicate with lesions in the genome; the enzymes responsible are also covered. Finally, we present examples of modern multilevel understanding of the cell function and malfunction in the wake of genotoxic assaults such as oxidative stress, abiotic environmental stress, and DNA-damaging plant toxins.

Insight on Genotoxicity

Author : Shiv Shankar Shukla
File Size : 68.8 MB
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Genetic toxicology is considered to be an important assessment tool as there is genetic impact of artificial chemicals. Insight on Genotoxicity discusses testing, mechanism, prediction, and bioindicator of genotoxicity taking into consideration recent advances in nano-engineered particles. Corollary of DNA dent is also discussed in detail taking into consideration the impact of ICH guidelines on genotoxicity testing, which is important for drug discovery innovation and development. Perspective review of genotoxicity evaluation in phytopharmaceuticals has been mentioned along with the prevention of genotoxicity in brief viewpoint. Salient Features Presents methods, standard protocols, and guidelines for genotoxicity testing Examines the impact of ICH Guidelines on genetic toxicity testing which is a regulatory requirement for drug discovery and development Defines appropriate strategies about advances in in vivo genotoxicity testing which have been listed along with progress and prospects Discusses advancement in the high-throughput approaches for genotoxicity testing Details computational prediction of genotoxicity with consideration of mutagenicity, chromosomal damage caused and strategies for computational prediction in drug development

Induced Effects Of Genotoxic Agents In Eukaryotic Cells

Author : Toby G Rossman
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This book provides an understanding of the consequences of induced proteins in the toxicological response of cells to chemical and radiation damage to DNA and will be helpful in creating proper mathematical models for extrapolation to low doses and assessing human exposure or cellular injury.

Environmental Damage to DNA and the Protective Effects of Phytochemicals

Author : Bechan Sharma
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Environmental Damage to DNA and the Protective Effects of Phytochemicals provides information on the toxicity of natural as well as synthetic chemicals in the living systems. These can lead to DNA damage and the emergence of serious consequences or manifestations causing varied health hazards. In addition, the ten chapters of the book reflect on the possible applications of plants or plant extracts to impart protection for living cells from the xenobiotics-mediated DNA damage. The book offers comprehensive coverage of the many essential topics in the subject including: Environmental factors and DNA damage Molecular mechanisms associated with DNA damage by various environmental (Physical, Chemical and Biological) factors Synergistic effects of environmental factors Phytochemicals acting both as DNA protectants and genotoxicants Experimental models for the study of the genotoxic potential of environmental factors and protection by phytochemicals This book connects readers who possess a life sciences background to the current understanding, concept and mechanisms involved in environmental-factors-mediated DNA damage. Scientific terms are introduced, defined, described and placed appropriately in the text. The protective effect of some plant extracts/phytochemicals has also been included. Environmental Damage to DNA and the Protective Effects of Phytochemicals is intended to cater the need of BSc, MSc and research students who are striving to discover the mechanism(s) associated with protection of DNA by plant-based chemicals. This is the first edition of our book and the valuable suggestions and comments from the readers are solicited.

Xenobiotic Metabolism and Markers of Genotoxicity in Regulatory Non vertebrate Ecotoxicological Test Species

Author : Rhiannon Mary David
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The Chemical Biology of DNA Damage

Author : Nicholas E. Geacintov
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Bringing the power of biochemical analysis to toxicology, this modern reference explains genotoxicity at the molecular level, showing the links between a DNA lesion and the resulting cellular or organismic response. Clearly divided into two main sections, Part 1 focuses on selected examples of important DNA lesions and their biological impact, while the second part covers current advances in assessing and predicting the genotoxic effects of chemicals, taking into account the biological responses mediated by the DNA repair, replication and transcription machineries. A ready reference for biochemists, toxicologists, molecular and cell biologists, and geneticists seeking a better understanding of the impact of chemicals on human health.