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The varying cancer incidence from country to country and region to region suggests that en vironmental factors play a considerable role in the aetiology of cancer. Whether these factors in the environment moderate the effect of car cinogenic chemicals or whether they might them selves be carcinogenic is not known at the present time. What is known is that there are various chemicals, both naturally occurring and man-made, which can induce cancer in man. In the Western world estimates vary as to how much cancer is occupational in origin; the figures range from 1% to 40%. It is our feeling that probably about 10% of cancer has a direct oc cupational origin. Nevertheless this number is considerable and it behoves us therefore to identify those chemicals which are carcinogenic and to reduce human exposure. Recent work on the mode of action of carcinogenic chemicals suggests that the majority exert their effect through an activation step to give elec trophilic metabolites. Such metabolites have as a common feature the ability to react with cel lular nucleophiles to give covalently bound products. Such reaction will occur after carcino gen treatment of animals with nucleic acids par ticularly in target organs. It is reaction with nucleic acids that provides the basis of a num ber of short-term tests for carcinogens, since the basic composition of DNA is similar in micro-organisms and in human cells.
Despite increasing knowledge of human nutrition, the dietary contribution to cancer remains a troubling question. Carcinogens and Anticarcinogens assembles the best available information on the magnitude of potential cancer riskâ€"and potential anticarcinogenic effectâ€"from naturally occurring chemicals compared with risk from synthetic chemical constituents. The committee draws important conclusions about diet and cancer, including the carcinogenic role of excess calories and fat, the anticarcinogenic benefit of fiber and other substances, and the impact of food additive regulation. The book offers recommendations for epidemiological and diet research. Carcinogens and Anticarcinogens provides a readable overview of issues and addresses critical questions: Does diet contribute to an appreciable proportion of human cancer? Are there significant interactions between carcinogens and anticarcinogens in the diet? The volume discusses the mechanisms of carcinogenic and anticarcinogenic properties and considers whether techniques used to evaluate the carcinogenic potential of synthetics can be used with naturally occurring chemicals. The committee provides criteria for prioritizing the vast number of substances that need to be tested. Carcinogens and Anticarcinogens clarifies the issues and sets the direction for further investigations into diet and cancer. This volume will be of interest to anyone involved in food and health issues: policymakers, regulators, researchers, nutrition professionals, and health advocates.
Mutagenicity: Assays and Applications presents an extensive examination of the detection, assessment and future of mutagenicity, particularly as it concerns human health and the environment. Chapters focused on specific types of mutagens or testing methods for their detection collectively explore the current state of human and environmental mutagenesis, future perspectives and regulatory needs. The test procedures for measuring mutagenicity, their advantages and limitations are described with practical and procedural detail, along with their presentation and data processing aspects. It is an essential reference covering the breadth and depth of the field of mutagenicity studies and regulation. By providing both important introductory material and practical assays and applications, this book is useful to graduate students, academic and industry researchers and regulators at various stages of their careers, leading to improved risk assessment and regulation. - Presents an up-to-date and in-depth review of the current state of mutagenesis research - Draws upon the combined experience and expertise of an international group of highly respected editors and chapter authors - Provides an introduction to the concept of mutagenesis with particular consideration given to novel chemicals and materials
The recent surge of interest in designing, validating, and implementing short-term tests for carcinogens has been spurred by the fairly convincing correlation be tween the carcinogenicity and mutagenicity of chemicals and physical agents and by the assumption that DNA alteration, mutations, and chromosome aberrations are somehow involved in neoplastic transformation. Moreover, it has been tacitly assumed that the mutagenic capacity alone of compounds would induce regulatory agencies to pass rules for their removal from the environment and would lead the public to avoid them. The actual response, however, is quite different. Governmental departments shy away from making any decisions on the basis of in vitro test systems. The public at large is becoming irritated by daily an nouncements that many of their cherished habits could adversely affect their health. Industry appears to feel threatened and may reduce its search for new beneficial chemicals. The reluctance to accept wholeheartedly the mutagenicity tests for the detection of carcinogens is partly due to uncertainty about the in volvement of mutations in neoplastic transformation, partly due to the present difficulty of extrapolating results from various endpoints obtained on numerous organisms to man, and partly due to a multitude of complex events that lead in vivo to the evolvement of benign or malignant tumors.
This open access book presents recent advances in the pure sciences that are of significance in the quest for alternatives to the use of animals in research and describes a variety of practical applications of the three key guiding principles for the more ethical use of animals in experiments – replacement, reduction, and refinement, collectively known as the 3Rs. Important examples from across the world of implementation of the 3Rs in the testing of cosmetics, chemicals, pesticides, and biologics, including vaccines, are described, with additional information on relevant regulations. The coverage also encompasses emerging approaches to alternative tests and the 3Rs. The book is based on the most informative contributions delivered at the Asian Congress 2016 on Alternatives and Animal Use in the Life Sciences. It will be of value for those working in R&D, for graduate students, and for educators in various fields, including the pharmaceutical and cosmetic sciences, pharmacology, toxicology, and animal welfare. The free, open access distribution of Alternatives to Animal Testing is enabled by the Creative Commons Attribution license in International version 4: CC BY 4.0.
This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.
The present survey comprises today‘s knowledge of environmental pollution in particular of the atmosphere by PAH and of the biological effects of this class of substance, putting special emphasis on their carcinogenic activity. The research data and conclusions derived therefrom are meant to assist the government of the Federal Republic of Germany in determining an air quality standard.
but also the possibility of intervention in specific stages. In Human behavior, including stress and other factors, plays an important role in neoplasia, although too little is known addition, variables which affect cancer development as well on the reasons for such development. Carcinogens, which as some endogenous factors can be better delineated help initiate the neoplastic process, may be either synthetic through such investigations. The topics of this volume encompass premalignant non or naturally-occurring. Cancer causation may be ascribed to invasive lesions, species-specific aspects of carcinogenicity, certain chemicals, physical agents, radioactive materials, viruses, parasites, the genetic make-up of the organism, and radiation, viruses, a quantum theory of carinogenesis, onco bacteria. Humans, eumetazoan animals and vascular plants genes, and selected environmental carcinogens. are susceptible to the first six groups of cancer causes, whe reas the last group, bacteria, seems to affect only vascular plants. Neoplastic development may begin with impairment ofJmdy defenses by a toxic material (carcinogen) which acts as an initiator, followed by promotion and progression to an overt neoplastic state. Investigation of these processes Series Editor Volume Editor allows not only a better insight into the mechanism of action Hans E. Kaiser Elizabeth K. Weisburger vii ACKNOWLEDGEMENT Inspiration and encouragement for this wide ranging project on cancer distribution and dissemination from a comparative biological and clinical point of view, was given by my late friend E. H. Krokowski.
This volume will provide a contemporary account of advances in chemical carcinogenesis. It will promote the view that it is chemical alteration of the DNA that is a route cause of many cancers. The multi-stage model of chemical carcinogenesis, exposure to major classes of human carcinogens and their mode-of-action will be a focal point. The balance between metabolic activation to form biological reactive intermediates and their detoxification, ensuing DNA-lesions and their repair will be profiled. It will describe the chemical changes that occur in DNA that result from endogenous insults including epigenetic changes that lead to gene silencing. It will describe major mechanisms of mutagenesis, affects on tumor suppressor genes and proto-oncogenes, and how cell-cycle check points can be by-passed by the "stealth-like" properties of chemical carcinogens. Environmental agents that can promote tumor formation will be discussed. The monograph will have wide appeal as a knowledge base for graduate students, post-doctoral fellows and faculty interested in this aspect of cancer causation and research.