Carcinogenesis and Mutagenesis Testing

Cancer has become the most critical health problem in the United States. It is expected that 25% of the people will develop this dread disease, and many of these will die from the malady. The causes of cancer are varied, but the best estimate available is that 70--90% arise from environmental factors. These statistics have triggered widespread governmental action along two lines: (l) An effort to identify those chemicals and conditions that give rise to malignant processes has been mounted by the Carcino genesis Testing Program, the National Cancer Program, and subse quently, the National Toxicology Program. (2) Regulatory laws have been enacted that are administered by agencies such as TSCA, FIFRA, EPA, FDA, OSHA, and so on, whose mission is to minimize public ex posure to carcinogens. Since direct verification that specific chemicals induce cancer in hu of unanticipated expo mans is necessarily limited to known incidences sure and is therefore rare, most chemicals are identified as carcinogens only by laboratory experiments. At present, the only accepted procedure is long-term animal bioassay, and not only are these studies expensive and time-consuming, but current worldwide resources permit the evalua tion of only 300-400 chemicals per year, a miniscule amount compared to what is available in the commercial world: 30,000 existing chemicals, with approximately 700 new such materials being introduced every year.

Zusammenfassung
This text provides both an overview of the fundamental biology of carcinogenesis and mutagenesis testing, presenting a highly practical collection of all the major laboratory assays.

Inhalt
I: The Fundamental Biology.- Section A: Mutagenesis and Other Short-Term Tests.- 1 An Overview of Short-Term Testing.- 2 Genetic Toxicology: Applications and Testing Strategies.- 3 Consequences of Genotoxic Effects.- 4 In Vitro Cell Transformation: An Overview.- 5 Lung Tumors in Mice.- 6 Tissue Genotoxic Effects.- Section B: Carcinogenesis.- 7 Basic Principles of Chemical Carcinogenesis.- 8 Pathology of Toxic, Preneoplastic, and Neoplastic Lesions.- 9 Carcinogen Bioassay Design.- 10 Evaluation and Interpretation of Carcinogenesis Bioassay Results.- II: Practical Carcinogenesis and Mutagenesis Assay Methodology.- Section A: Gene Mutation Assays.- 11 Bacterial Reverse and Forward Mutation Assays.- 12 Yeast Assays in Mutagen and Carcinogen Screening.- 13 Mouse Lymphoma Cell Assays.- 14 Chinese Hamster Ovary Mutation Assays.- 15 Drosophila Assay Systems.- Section B: DNA Damage and Repair Assays.- 16 Detection of DNA Damage and Repair in Bacteria.- 17 Mammalian DNA Repair Assays.- Section C: Cytogenetic Assays.- 18 Cytogenetic Assays: Aberrations and SCE Techniques.- Section D: Transformation Assays.- 19 In Vitro Transformation Assays Using Mouse Embryo Cell Lines: Balb/c-3T3 Cells.- 20 In Vitro Transformation Assays Using Mouse Embryo Cell Lines: C3H/10T1/2 Cells.- 21 In Vitro Transformation Assays Using Diploid Syrian Hamster Embryo Cell Strains.- Section E: Short-Term In Vivo Carcinogenesis Assays.- 22 Lung Tumor Assay.- 23 Tissue Genotoxic Effects: Methods.- Section F: Conduct of Carcinogen Bioassays.- 24 Conduct of Carcinogen Bioassays.