This monograph provides a contemporary account of advances in chemical carcinogenesis. It promotes the view that it is alteration of the DNA by endogenous and exogenous carcinogens that ultimately leads to sporadic mutations which are a root cause of many human cancers. It deals with the metabolic activation of common classes of chemical carcinogens (tobacco carcinogens, heterocyclic amines, polycyclic aromatic hydrocarbons) and their detoxication. It describes the DNA-adducts that ensue and their repair mechanisms. It covers advances in structural-biology that provide a glimpse of both the DNA-repair process and the by-pass of DNA-lesions and how this informs the mutational code. It also deals with the concepts of chemoprevention and biomarkers for biomonitoring human exposure. Many contemporary texts on the biology of cancer now focus almost exclusively on the molecular and cell biology of the disease and do not cover the initiating (DNA damaging events) of chemical carcinogenesis in depth. It is with this perceived gap-in knowledge that world experts in their particular fields have contributed to this monograph. This monograph will be an important reference re-source for students in training, postdoctoral scientists, and senior scientists knowledgeable in the field.

Zusammenfassung

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.

Inhalt

Historical Overview of Chemical Carcinogenesis.- Multistage Carcinogenesis.- Tobacco Smoke Carcinogens and Lung Cancer.- Mechanisms of Estrogen Carcinogenesis: Modulation by Botanical Natural Products.- Heterocyclic Amines: Potential Human Carcinogens.- Aflatoxins and Hepatocellular Carcinoma.- Metabolic Activation of Chemical Carcinogens.- Detoxication of Chemical Carcinogens and Chemoprevention.- Covalent Polycyclic Aromatic Hydrocarbon-DNA Adducts, Carcinogenicity, Structure and Function.- Oxidation and Deamination of DNA by Endogenous Sources.- Lipid Peroxide-DNA Adducts.- Chemical Carcinogenesis and Epigenetics.- Nucletoide Excision Repair From Bacteria to Humans: Structure-Function Studies.- Base Excision Repair: Role of DNA Polymerase b in Late Stage Base Excision Repair.- O6-Alkylguanine-DNA alkyltransferase.- By-Pass DNA Polymerases.- Mutagenesis: The Outcome of Faulty Replication of DNA.- p53 and Ras-Mutation <