The recent surge of interest in designing, validating, and implementing short-term tests for carcinogens has been spurred by the fairly convincing correlation be tween the carcinogenicity and mutagenicity of chemicals and physical agents and by the assumption that DNA alteration, mutations, and chromosome aberrations are somehow involved in neoplastic transformation. Moreover, it has been tacitly assumed that the mutagenic capacity alone of compounds would induce regulatory agencies to pass rules for their removal from the environment and would lead the public to avoid them. The actual response, however, is quite different. Governmental departments shy away from making any decisions on the basis of in vitro test systems. The public at large is becoming irritated by daily an nouncements that many of their cherished habits could adversely affect their health. Industry appears to feel threatened and may reduce its search for new beneficial chemicals. The reluctance to accept wholeheartedly the mutagenicity tests for the detection of carcinogens is partly due to uncertainty about the in volvement of mutations in neoplastic transformation, partly due to the present difficulty of extrapolating results from various endpoints obtained on numerous organisms to man, and partly due to a multitude of complex events that lead in vivo to the evolvement of benign or malignant tumors.

Inhalt

Viral Systems.- 1. A Biochemical Phage Induction Assay for Carcinogens.- 2. Detection of DNA-Modifying Agents by Analyzing the Lesions Introduced into Purified PM2 DNA.- 3. Reactivation of Viruses.- DNA.- 4. Metabolic Activation of Nitroheterocyclic Compounds in Bacteria and Mammalian Cells.- 5. Utilization of the Alkaline Elution Assay as a Short-Term Test for Chemical Carcinogens.- 6. DNA Synthesis Inhibition in Mammalian Cells as a Test for Mutagenic Carcinogens.- 7. DNA Repair Synthesis (UDS) as an in vitro and in vivo Bioassay to Detect Precarcinogens, Ultimate Carcinogens, and Organotropic Carcinogens.- 8. Multi-well Assay for Unscheduled DNA Synthesis Using Human Diploid Fibroblasts.- 9. Sucrose Gradients: An Assay for DNA Damage.- 10. The Testicular DNA-Synthesis Inhibition Test (DSI Test).- Microbial Systems.- 11. The Salmonella Mutagenicity Test: An Overview.- 12. Applications of the Salmonella/Microsome Assay.- 13. Determination of Genotoxic Activity Using DNA Polymerase-Deficient and -Proficient E. coli.- 14. The Nucleotide-Permeable Escherichia coli: A Model System that Responds to DNA-Binding Carcinogens, Mutagens, and Antitumor Agents with DNA Excision Repair or with Inhibition of Replicative DNA Synthesis.- 15. The Yeast Saccharomyces cerevisiae: An Assay Organism for Environmental Mutagens.- Appendix I: Protocol for a Haploid Yeast Reversion Test for Assaying Mutagens.- 16. Induction and Genetic Characterization of Specific Locus Mutagens in the ad-3 Region in Two-Component Heterokaryons of Neurospora crassa.- 17. Neurospora and Environmentally Induced Aneuploidy.- Higher Plants.- 18. Plant Genetic Test Systems for the Detection of Chemical Mutagens.- Chromosomes.- 19. A Short-Term Cytogenetic Test for Genetic Instability in Humans.- 20. The Sister Chromatid Exchange Test.- 21. The Micronucleus Assay. I. In Vivo.- 22. The Micronucleus Assay. II. In Vitro.- 23. Automation in Cytogenetics.- Mammalian Systems.- 24. Mutagenesis Studies in Diploid Human Cells with Different DNA-Repair Capacities.- 25. Liver Culture Indicators for the Detection of Chemical Carcinogens.- 26. An Escherichia coli Differential Killing Test for Carcinogens Based on a uvrA recA lexA Triple Mutant.- 27. Detection of Carcinogens Using the Fluctuation Test with S9 or with Hepatocyte Activation.- Transformation.- 28. In Vitro Mammalian Cell Transformation for Identification of Carcinogens, Cocarcinogens, and Anticarcinogens.- 29. The Use of Cryopreserved Syrian Hamster Embryo Cells in a Transformation Test for Detecting Chemical Carcinogens.- 30. Assay of Chemically Induced Transformation of Human Cells.- 31. Chemical-Viral Interactions: Enhancement of Viral Transformation by Chemical Carcinogens.- 32. The Calcium Independence of Neoplastic Cell Proliferation: A Promising Tool for Carcinogen Detection.- Entire Animals.- 33. Induction of a Resistant Preneoplastic Liver Cell as a New Principle for a Short-Term Assay in vivo for Carcinogens.- 34. Recent Achievements with Drosophila as an Assay System for Carcinogens.- 35. Strategy for Breeding Test Animals of High Susceptibility to Carcinogens.- 36. Methods for Human and Murine Sperm Assays.- Cocarcinogens, Anticarcinogens, and Promoters.- 37. In vitro Assay for Tumor Promoters.- 38. Inhibition of Chemical Mutagenesis: An Application of Chromosome Aberration and DNA Synthesis Assays Using Cultured Mammalian Cells.- 39. Detection of Cocarcinogens and Anticarcinogens with Microbial Mutagenicity Assays.- 40. The Use of A Bacterial Assay to Identify Which Agents Modify Carcinogen-Induced Mutagenesis.- Concepts.- 41. Quantitative Measures of Induced Mutagenesis.- 42. Tests for Potential Carcinogens: Unresolved Problems.- 43. Mutagenicity Testing: Problems in Application.- 44. Short-Term Genetic Tests Extended to the Human.