"Biologically Based Methods for Cancer Risk Assessment", an Advanced Research Workshop, (ARW) sponsored by the North Atlantic Treaty Organization (NATO) was held in Corfu, Greece in June, 1989. The intent of the workshop was to survey available pharmacokinetic and pharmacodynamic methods in cancer risk assessment and identify methodological gaps and research needs for biologically based methods in cancer risk assessment. Incorporation of such methods represents one of the most challenging areas for risk assessment. The workshop included an international group of invited experts in the field and provided for a dynamic exchange of ideas and accomplishments. Some of the major topics discussed were: * Inventory of available pharmacokinetic and pharmacodynamic methods for cancer risk assessment. * Identification of methodology gaps and research needs in biologically based methods in cancer risk assessment. * Development of a general framework to guide future cancer risk assessment research. This book is a compilation of the papers presented at the workshop and is intended to provide guidance for future research to reduce uncertainties in the cancer risk assessment process. The primary sponsorship of this ARW by NATO and the advice and cooperation of Dr. C. Sinclair of the Scientific affairs Division are gratefully acknowledged. Acknowledgement is also given to the National Science Foundation for its support. The organization of the ARW and the preparation of this book have required considerable help from many other sources.
Table of ContentsResearch Needs for Biologically Based Risk Assessment.- Biological Bases for Cancer Models.- Multistage Models for Cancer Risk Assessment.- Understanding Multi-Stage Carcinogenesis at the Molecular Level: Notes on Recent Progress.- The Use of Enzyme-Altered Foci for Risk Assessment of Hepatocarcinogens.- Pathogenic Interrelationship of Focal Lesions, Nodules, Adenomas and Carcinomas in the Multistage Evolution of Azaserine-Induced Rat Pancreas Carcinogenesis.- Phenotypic Cellular Changes in Multistage Carcinogenesis.- Interspecies Extrapolation of Pharmacokinetics.- Interspecies Extrapolation.- Comparative Carcinogenesis: Is There a Theoretical Approach to Inter-Species Similarity.- Biological Basis for Interspecies Extrapolations of Halogenated Solvents and of 1,3-Butadiene.- Species-Specific Inhalation Pharmacokinetics of 2-Nitropropane, Methyl Ethyl Ketone, and n-Hexane.- Promotion as a Factor in Carcinogenesis.- Overview of Promotion as a Mechanism in Carcinogenesis.- Hepatocarcinogenesis by Non-Genotoxic Compounds.- The Role of Inhibited Intercellular Communication in Carcinogenesis: Implications for Risk Assessment From Exposure to Chemicals.- Comparative Analyses of the Timing and Magnitude of Genotoxic and Nongenotoxic Cellular Effects in Urinary Bladder Carcinogenesis.- Alterations in Gene Expression in Mouse Hepatocarcinogenesis.- Screening for Carcinogenesis.- Medium-Term Bioassay Models for Environmental Carcinogens Two Step Liver and Multi-Organ Carcinogenesis Protocols.- The Use of Aldh Induction as a Carcinogenic Risk Marker in Comparison With Typical in Vitro Mutagenicity System.- Expression of Inducible Cytochrome P-450 mRNAs During Promotion of Expermential Chemical Hepatocarcinogenesis.- An In Vitro Approach for Interspecies Extrapolation Using Animal and Human Airway Epithelial Cell Culture.- Cancer Risk Assessment.- Assement of Low-Exposure Risk from Carcinogens: Implications of the Knudson-Moolgavkar Two-Critical Mutation Theory.- A Biological Data Base for Methylene Chloride Risk Assessment.- Computer Simulation of Chemical Carcinogenesis.- Determination of Carcinogen Exposure by Immunological Techniques.- Risk Estimation for Leukemogenic Drugs.- Contributors.