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.

The use of exocyclic adducts as biomarkers offers a promising tool in studies of cancer etiology and prevention, particularly for human neoplasias in which the causative factors and mechanisms are still poorly understood. Presentations at an international conference, which resulted in this volume, comprise a comprehensive treatise on the current state of the art and scientific information on exocyclic DNA adducts. The volume includes sections on ultra sensitive detection methods, formation from exogenous and endogenous sources, DNA repair, physical chemical approaches to structural elucidation, and use as biomarkers and their role in mutagenesis and carcinogenesis.

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.

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.

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.

This work has been selected by scholars as being culturally important, and is part of the knowledge base of civilization as we know it. This work is in the "public domain in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. Scholars believe, and we concur, that this work is important enough to be preserved, reproduced, and made generally available to the public. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant.

This book is a printed edition of the Special Issue " Chemically-Induced DNA Damage, Mutagenesis, and Cancer" that was published in IJMS

During the early 1930s, when I was a graduate student and later a post-doctoral researcher at the National Research Council for the University of Wisconsin at Madison, we had the opportunity to get acquainted with many graduate students from China who were sent to the University for training in modern basic sciences as well as social sciences. The University of Wisconsin continues to graduate a large number of Chinese students. Economic conditions in the 1930s were very precarious for the United States and other parts of the world. Many of us students grew closer together because we were living on similarly tight budgets. As a matter of fact, we subleased a part of our apartment in Madison to some Chinese graduate students. This was a very nice opportunity for us to learn about the scientific and cultural back ground of our Chinese friends. Many of them came from the interior of China and had had very little opportunity to become acquainted with people from a western culture. Living with these students was a very pleasant and educational experience which gave us a good pic ture of the cultural life and educational system of China at that time--an intimate picture that one normally would not see without travelling in that country.