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As chemical exposures and cancer rates increase worldwide, there is a need for students, researchers, public health professionals, and physicians to understand the mechanisms connecting exposure with human cancer risk. This new book is an essential reference, as well as introduction to the field of chemical carcinogenesis, with particular focus on DNA damage as a critical link between exposure and disease, and emphasis on biomarkers associated with cancer risk in humans. In addition to DNA damage, related topics covered include metabolism of selected chemical carcinogens, exposure-induced epigenetic changes, cancer-associated mutations and reduction of DNA damage and cancer risk by chemoprevention. The book is designed to be a comprehensive guide to basic principles, a teaching tool for academics, and a map for the development of protective mechanisms to reduce human cancer risk.

First published in 1979, Chemical Carcinogenesis and DNA is an essential guide to the relationship between mutagens, carcinogens and our own genetic makeup. Covering a range of associated topics, this volume provides information that would prove most beneficial for practitioners of medicine and students alike.

An in-depth exploration of Benzene Carcinogenicity including source, measurement, analysis, and clinical conclusions.

This book reviews the main concepts concerning DNA damage due to environmental carcinogens, the effects of DNA damage on DNA replication using a single DNA polymerase or DNA replisome, and the effects of carcinogens on various cell activities. It also introduces the detailed protocols for bypassing DNA damage. As we know, various environmental carcinogens are produced as a result of industry, agriculture, chemical engineering and vehicle exhaust in our daily life. It has been reported that the environmental carcinogens can be connected to tumors and cancer, directly threatening human health. In this regard, DNA replication is highly susceptible to damage. This book provides graduate students and researchers with an overview of the effects of environmental carcinogens on DNA replication and biological activities in cells. It offers important information for research in the areas of biochemistry, cell biology, medicine, toxicology and public health.

This book re-evaluates epidemiological and occupational health studies, experimental studies in animals and in vitro experiments relating to the toxicity of 27 metal and metalloid elements for which evidence of carcinogenicity has been presented. Human carcinogenic risk is substantiated in relation to arsenic, beryllium, thorium, chromium, radioactive elements, probably lead, and some nickel and cobalt compounds, and respirable silica particles, but the carcinogenicity of iron, aluminium, titanium, tungsten, antimony, bismuth, mercury, precious metals, and certain related compounds in humans is unresolved. The toxicity and carcinogenicity of each element is specific but correlates poorly with its position in the Periodic Table. Carcinogenicity differs according to the valency of the ion and its ability to interact with and penetrate membranes in target cells and to bind, denature or induce mutations by genotoxic or epigenetic mechanisms. This important text comprehensively examines each of the elements providing detailed information on the carcinogenicity and toxicity and detailing the most up-to-date research in this area. The book is an essential tool for toxicologists, medicinal and biochemists, and environmental scientists working in both industry and academia.

Toph's in Chemical Mutagenesis is a new series dedicated to studies in the areas of environmental chemical mutagenesis and genetic toxicology. In this series we will explore some of many topics that are emerging in these rapidly developing fields. The purpose of the present volume is to attempt to organize and compare the genotoxic properties of the N-nitroso compounds. This is a particularly interesting class of compounds because of the problems encountered with the Salmonella assay of Ames in generating both false positive and false negative results. The battery approach using a number of assay systems seems more appropriate to evaluate chemicals in this class. Topics to be discussed in other volumes in this series include single-cell mutation monitoring systems, the detection of genetic damage in mammalian germ cells, the mutagenicity of pesticides, problems in monitoring human populations in genetic toxicology, and a glossary of terms in genetic toxicology. All of these books are in various stages of development and should appear within the next few years. Frederick J. de Serres Series Editor vii Preface During the past ten years there has been an explosive development in the number of short-term tests to predict the biological risks, especially risks of cancer, in exposure to xenobiotic chemicals. The number of published articles in this area has reached many thousands a year and there are several new journals devoted almost entirely to the presentation of the results obtained in these tests.

Nearly half of all Americans will be diagnosed with an invasive cancer—an all-too ordinary aspect of daily life. Through a powerful combination of cultural analysis and memoir, this stunningly original book explores why cancer remains so confounding, despite the billions of dollars spent in the search for a cure. Amidst furious debates over its causes and treatments, scientists generate reams of data—information that ultimately obscures as much as it clarifies. Award-winning anthropologist S. Lochlann Jain deftly unscrambles the high stakes of the resulting confusion. Expertly reading across a range of material that includes history, oncology, law, economics, and literature, Jain explains how a national culture that simultaneously aims to deny, profit from, and cure cancer entraps us in a state of paradox—one that makes the world of cancer virtually impossible to navigate for doctors, patients, caretakers, and policy makers alike. This chronicle, burning with urgency and substance leavened with brio and wit, offers a lucid guide to understanding and navigating the quicksand of uncertainty at the heart of cancer. Malignant vitally shifts the terms of an epic battle we have been losing for decades: the war on cancer.

This book originated in numerous Gordon Research Conferences and many other meetings of scientists working in chemistry, biophysics, biochemistry, and biology related to mutagenesis and carcinogenesis. It seemed the appro­ priate time to sit back and summarize the results of several decades of research in laboratories in different countries. We are very grateful to the Rockefeller Foundation for inviting us to formulate and begin writing the book at the Center for International Studies in Bellagio, Italy, where we were Resident Scholars. We are fortunate to have had the assistance of so many colleagues around the world who cheerfully sent original data, figures, and preprints and lis­ tened patiently to us as we worked out the various conflicting ideas in this fast-moving. field. The names of these scientists are found within the tables, figures, and references. There is one person whose contributions we especially wish to acknowl­ edge. Professor Heinz Fraenkel-Conrat was present at the inception of this book and throughout the writing encouraged and criticized in apprOximately equal proportion. Finally, his editing and amalgamation of our two styles gave us great comfort. B.S. D.G.

Initiation of cancer in the cell is experimentally related to action of chemicals and radiation. For understanding the first steps of this interaction, approved methods from quantum theory and solid state physics are applied by the authors.The approach of this book is interdisciplinary. Theoretical models are qualitatively applied. Known effects, like oncogene activation, anti-oncogenes, and disturbances of the cell's self-regulation are explained. The authors propose possible points of intervention in the cancer initiation process based on the theoretical considerations.

In the approach to the analysis of disease, including, of course, cancer, two major thrusts may be distinguished. These may be referred to, in shorthand, as agents and processes: the causative agents (chemical, microbial, physical, environmental, and psychosocial) and the organismic processes, initiated and furthered by the agents, culminating in observable pathology (at the macromolecular, cytological, histological, organ function, locomotor, and behavioral levels). The past 25 years, since the appearance of the first volume of the predecessor series (1) authored by the Editors of this present volume, have seen an impressive number of studies on chemicals (and other agents) as etiologic factors in the induction of cancer. The major emphasis has been on the discovery of many chemical carcinogens of widely different structures, their metabolism by various tissues and cells, and, in turn, their molecular-biochemical effects on the cells. This rapidly expanded body of information, as effectively covered in the predecessor volumes, is an excellent entree to the second half of the overall problem of chemical carcinogenesis, the processes. The active agents trigger a large array of molecular-biochemical alterations to which the target cells, target tissues, and target organisms respond in many select and common ways. This second major aspect of the induction of cancer by chemicals (and by other agents)- the sequence of cellular and tissue changes clearly relevant to cancer-remains the challenge for the future.

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 book is intended for anyone who cares about the health of people exposed to industrial pollutants. Attention is given to those pollutants which present a possible risk to the genetic material of exposed workers. Chapters are devoted to heavy metals such as arsenic, beryllium, cadmium, chromium, lead, mercury, nickel, etc.; insecticides (chlorinated, organophosphorus, and carbonate insecticides); monomers such as vinyl-chloride, acrylonitrile, styrene, vinylidene chloride, butadiene, chlorobutadiene, hexachlorobuta­ diene, etc.; and halogenated hydrocarbon solvents such as chloroform, carbon tetrachloride, trichloroethylene, I, 2-dichloroethane, tetrachloroethyl­ ene, dichloromethane, and I, I, I-trichloroethane. The main aim of this work is to provide the physician, the biologist, the pharmacologist, or anyone involved in genetic toxicology with a useful compendium of up-to-date information and references. Efforts are made to open the field to nonspecialists. An introductory chapter deals with the mechanisms whereby a given compound, reaching genetic material, either directly or indirectly, may increase the risk of a cancer developing in the exposed individual and of abnormalities being passed on to his or her progeny. Efforts are also made to allow easy and efficient reading for those who are not interested in detailed results. Comparative tables provide the following data on the compounds studied: chemical properties, production, occurrence, accepted standards in the industry, and positive or negative results with different test systems. Finally, senior research workers might find good descriptions in this book of the most recent results from mutagenesis and carcinogenesis testing in plant, nonmammalian, and mammalian systems.

Cellular transformation and carcinogenesis are considered a multistep process starting with DNA lesions and progressing through loss of cellular growth control and increase invasive and metastatic properties. This book focuses on the demonstration of important steps in carcinogenesis, ranging from chemical interaction of carcinogens with cellular DNA in experimental tumors and cell lines to the analysis of selected human tumors. Special importance is given to the clarification of mechanisms of DNA lesions caused by chemical carcinogens and UV irradiation. Leading scientists describe in review articles the actual state of the art in their specific fields. The reader is informed of trends and scientific approaches to the recognition of pathogenetic mechanisms and factors in malignant tumors.