Polycyclic hydrocarbons and cancer

Polycyclic Hydrocarbons and Cancer, Volume 3 explores the link between polycyclic aromatic hydrocarbons (PAHs) and cancer based on research in the fields of chemistry, biology, and the medical and social sciences. Topics covered include the metabolism of polynuclear aromatic hydrocarbons; carcinogenicity of PAHs and their derivatives; the role of microsomal epoxide hydrolase in the biotransformation of PAHs; and biochemical effects of the phorbol ester tumor promoters and their implications for PAH carcinogenesis. This volume consists of eight chapters and begins with a discussion on the mechanisms of PAH metabolism in the marine environment. The use of X-ray crystallographic techniques in studying carcinogenic PAHs and their derivatives is then considered, along with the involvement of dihydrodiols and diol epoxides in the metabolic activation of PAHs other than benzo[a]pyrene; the role of microsomal epoxide hydrolase in PAH biotransformation; and drug detoxication in relation to the excretion mechanism of chemical carcinogens. The following chapters focus on the anticarcinogenic or inhibitory effects of a variety of chemicals on PAH carcinogenesis; the biochemical effects of the phorbol ester tumor promoters on PAH carcinogenesis; and epidemiology of PAHs, with emphasis on quantification of the cancer risk from cigarette smoking and air pollution. This monograph will be of interest to investigators and educators concerned with scientific aspects of PAH research; government officials and elected representatives as well as industry leaders who must confront and solve the problems related to PAHs; and others in the fields of chemistry, biology, and the medical and social sciences.

List of ContributorsPrefaceContents of Previous Volumes1 Polynuclear Aromatic Hydrocarbons and Their Metabolism in the Marine Environment I. Introduction II. PAH in the Marine Environment III. Monooxygenase Activity in Aquatic Species IV. Induction of Cytochrome P-450 V. Patterns of Metabolism of PAH VI. PAH Carcinogenesis in Marine Species VII. Environmental Health Implications VIII. Conclusion References2 X-Ray Crystallographic Studies on Carcinogenic Polycyclic Aromatic Hydrocarbons and Their Derivatives I. Introduction II. Polycyclic Aromatic Hydrocarbons III. Comparisons with Other Structures IV. Interactions of Carcinogens with Proteins V. Interactions of Carcinogens with Nucleic Acids VI. Summary References3 Involvement of Dihydrodiols and Diol Epoxides in the Metabolic Activation of Polycyclic Hydrocarbons Other than Benzo[a]Pyrene I. Introduction II. General Pathways of Hydrocarbon Metabolism III. Metabolic Activation involving Dihydrodiols and Diol Epoxides IV. Factors Affecting Dihydrodiol and Diol Epoxide Formation V. Factors Influencing Hydrocarbon Activation VI. Concluding Remarks References4 Microsomal Epoxide Hydrolase and Its Role in Polycyclic Aromatic Hydrocarbon Biotransformation I. Introduction II. Physical Characterization of Epoxide Hydrolase III. Biochemical Properties of Epoxide Hydrolase IV. Distribution and Regulation of Epoxide Hydrolase Activity V. Participation of Epoxide Hydrolase in Metabolic Activation and Deactivation of Polycyclic Aromatic Hydrocarbons VI. Conclusion References5 Glutathione, Glucuronide, and Sulfate Transferase in Polycyclic Aromatic Hydrocarbon Metabolism I. Introduction II. Conjugates of Polycyclic Aromatic Hydrocarbons (PAH) In Vivo III. Metabolites of PAH in Cultured Cells IV. GSH 5-Epoxide Transferase V. UDP-Glucuronyl Transferase VI. Sulfotransferase VII. Effects on Biological Activities of PAH VIII. Implications of Conjugation Reactions for Carcinogenesis IX. Conclusion References6 Modification of Polycyclic Aromatic Hydrocarbon Carcinogenesis I. Introduction II. Antioxidants III. Flavones IV. Halogenated Hydrocarbons V. Weakly or Noncarcinogenic PAH VI. Anti-inflammatory Steroids VII. Prostaglandin Synthesis Inhibitors VIII. Miscellaneous Agents IX. Summary References7 Biochemical Effects of the Phorbol Ester Tumor Promoters and Their Implications for Polycyclic Aromatic Hydrocarbon Carcinogenesis I. Introduction II. Initiation and Promotion III. Mimicry of Transformation and Enhancement IV. Modulation of Differentiation by Phorbol Esters V. Effect of Tumor Promoters on Blood Elements VI. Relationship of Tumor Promoters to Virus Transformation VII. Evidence that Cells Contain High-Affinity Phorboid Receptors: Possible Significance during Growth and Development VIII. Phorbol Ester-Induced Changes in Phospholipid Metabolism IX. Phorbol Esters and Calcium Metabolism X. Mediation by Ah Receptor of the Tumor-Promoting Activity of Polycyclic Aromatic Hydrocarbons XI. A Unified Theory of Initiation and Promotion References8 Epidemiology of Polycyclic Hydrocarbons: Quantifying the Cancer Risk from Cigarette Smoking and Air Pollution I. Introduction II. Cigarette Smoking and Lung Cancer III. Air Pollution and Lung Cancer IV. Conclusions ReferencesIndex

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