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.

About two centuries after the communication by Sir Percival Pott that the "chimney sweeper disease" was a cancer and its suggestion that active compounds of soot were the causative agents, and about one century after the description of urinary bladder cancer in dye workers, an enormous number of substances have been synthesized and have probably come into contact with man. Research in cancer prevention is of primary importance, and may receive continuous support from new discoveries on cancer etiology and pathogenesis. If one accepts the multistage model of chemical carcinogenesis, one has also to accept that many events occur between the contact of carcino genic compounds and their specific targets and the development of a clinically recognizable neoplasm. Thus, animal studies become essential to elucidate the different steps by which chemical carcinogens induce neoplasia. The analysis of these steps and the comparative evaluation of experimental models is essential to an understanding of pathogenesis.

During October 18-30, 1981, the second course of the International School of Pure and Applied Biostructure, a NATO Advanced Study Institute, was held at the Ettore Majorana Center for Scientific Culture in Erice, Italy, co-sponsored by the International Union Against Cancer, the Italian League Against Cancer, the Italian Ministry of Public Education, the Italian Ministry of Scientific and Technological Research, the North Atlantic Treaty Organization, the Italian National Research Council, the Sicilian Regional Government and two pharmaceutical Companies (Zambeletti and Farmitalia). The subject of the course was "Chemical Carcino genesis" with participants selected world-wide from 18 different countries. It is now eminently clear that.the bulk of human cancers are related to one of several types of environmental exposure. Of the environmental hazards, chemicals are among the best characterized carcinogens. However, how chemicals induce cancer is still poorly understood. Because of the magnitude of the problem and the ob vious need for a much more critical scientific analysis of the process by which cancer is induced (carcinogenesis), it was highly desirable to expose a greater number of scientists with varying background to some of the latest thinking in chemical carcino genesis. The course had this as its major objective and the re sulting book does reflect it.

Microsomes, Drug Oxidations, and Chemical Carcinogenesis, Volume II, documents the proceedings of the 4th International Symposium on Microsomes and Drug Oxidations held in Ann Arbor, July 1979. The symposium reviewed progress in the understanding of scientific and biomedical problems from a biochemical, biophysical, pharmacological, and toxicological perspective. Volume I contained 117 contributions made by researchers at the symposium, which were organized into three sections (Sections I-III). This second volume contains 122 contributions, divided into four sections (Sections IV-VII). The papers on Section IV examine the metabolic fate of oxygenated compounds. Section V provides studies on microsomal enzymes and lipid metabolism. Section VI includes papers on microsomal enzymes and toxicity of foreign compounds. Section VII covers microsomal enzymes and chemical mutagenesis and carcinogenesis. This book seeks to aid future progress in understanding the complexities of metabolic transformations by these versatile enzyme systems that act on physiologically important lipids as well as on a wide array of foreign substances, including drugs, anesthetics, industrial chemicals, food additives, pesticides, carcinogens, and nonnutrient dietary chemicals.

"chemical carcinogenesis" is the general title of the series of international meetings which are held, biannually, in sardinia (Italy) since 1981. Despite the generality of the title, the main effort of the scientific Committee has been to pursue a coherent line around one of the most distinguishing features of carcinogenesis: the "multifasic" development of the process. Given that many chemical compounds are known to cause "experimental cancer", many questions still remain unresolved or are given too simplistic answers. The very first question concerning the interaction between the chemical carcinogen and the molecular target in the cell is a debatable one despite the overwhelming literature in this field. It is certain that chemical carcinogens are toxic to cells and cause DNA damage: however it is still an open question as to how to relate these changes to the different stages of carcinogenesis including initiation. We have not to forget that 1/3 to 2/3 of the average life time of a given species elapses between the experimental administration of the carcinogen and the appearance of "cancer". The experimental manipulation of carcinogenesis through the use of "adequate biological models" has not simplified the problems about cancer, but it has led us to face the complexity of otherwise elementary biological properties, cell proliferation and differentiation. The understanding of this biological complexity is not just theoretical, but it may give us those adequate conceptual tools to approach "cancer" also from a medical point of view.

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.

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, ELIZABE1H CAVERT, 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.