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.

I have been privileged to witness and participate in the great growth of knowledge on chemical carcinogenesis and mutagenesis since 1939 when I entered graduate school in biochemistry at the University of Wisconsin Madison. I immediately started to work with the carcinogenic aminoazo dyes un der the direction of Professor CARL BAUMANN. In 1942 I joined a fellow graduate student, ELIZABETH CA VERT, in marriage and we soon commenced a joyous part nership in research on chemical carcinogenesis at the McArdle Laboratory for Cancer Research in the University of Wisconsin Medical School in Madison. This collaboration lasted 45 years. I am very grateful that this volume is dedi cated to the memory of Elizabeth. The important and varied topics that are reviewed here attest to the continued growth of the fields of chemical car cinogenesis and mutagenesis, including their recent and fruitful union with viral oncology. I feel very optimistic about the application of knowledge in these fields to the eventual solution of numerous problems, including the detection and estimation of the risks to humans of environmental chemical carcinogens and re lated factors.

With a weight-of-the-evidence approach, cancer risk assessment indentifies hazards, determines dose-response relationships, and assesses exposure to characterize the true risk. This book focuses on the quantitative methods for conducting chemical cancer risk assessments for solvents, metals, mixtures, and nanoparticles. It links these to the basic toxicology and biology of cancer, along with the impacts on regulatory guidelines and standards. By providing insightful perspective, Cancer Risk Assessment helps researchers develop a discriminate eye when it comes to interpreting data accurately and separating relevant information from erroneous.

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.

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.

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.

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.