Chemical Carcinogenesis

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.

Inhalt

Section I: Chemicals as Carcinogens.- Chemical Carcinogenesis by Polycyclic Aromatic Hydrocarbons.- N-Substituted Aromatic Compounds.- Metabolic Epoxidation of Aflatoxin B1 and Its Metabolites: Patterns of DNA Adduct Formation and Removal in Relation to Biological Effects.- The Problematic Use of Chemical Class Controls in Absence of Information on the Underlying Mechanism.- Discussion.- Section II: DNA Adducts.- DNA Lesions: Nature and Genesis.- DNA Alkaline Elution: Physical Basis of the Elution Process and Validation of this Method as a Screeing Procedure to Identify Chemical Carcinogens.- DNA Fragmentation: Its Predictivity as a Short Term Test.- Measurement of Viscous and Elastic Components of Native DNA Fiber Following Carcinogen Administration.- Initiation of Experimental Liver Carcinogenesis by Chemicals: Are the Carcinogen Altered Hepatocytes Stimulated to Grow into Foci by Different Selection Procedures Identical?.- Influence of DNA Conformation on DNA Methylation and the Direct Binding of N-Methyl-N-Nitroso-N1-Nitro-Guanidine.- Genotoxic Effects of Drugs: Experimental Findings Concerning Some Chemical Families of Therapeutic Relevance.- Discussion.- Section III: Chemicals as Promotors.- Phenobarbital and Other Liver Tumor Promotors.- Molecular Mechanisms of Multistage Carcinogenesis.- Alterations of Liver Architecture in Mice Treated with Anabolic Androgens and Diethylnitrosamine.- Discussion.- Section IV: Carcinogenesis as Multistep Process.- Some Critical Consideration Concerning the Sequential Analysis of Carcinogenesis with Chemicals.- Benign and Malignant Tumor Induction in Mouse Skin.- Progress in the Study of In Vitro Neoplastic Transformation.- Pulse-Carcinogenesis by Ethylnitrosourea in the Developing Rat Nervous System: Molecular and Cellular Mechanisms.- Chromatin, Nuclei and Water: Alterations and Mechanisms for Chemically-Induced Carcinogenesic.- The Cytoskeleton: An Intermediate in the Expression of the Transformed Phenotype in Malignant Cells.- Discussion.- List of Participants.- Contributor Index.