ABSTRACT
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
4.1.1 General Aspects of DNA Adduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 4.1.2 Categorization of DNA Adducts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 4.1.3 Relationships between DNA Adducts and Mutations . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
4.2 Techniques for Measuring DNA Adducts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 4.2.1 Radiolabeled Chemical Binding Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 4.2.2 Mass Spectroscopic Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 4.2.3 Synchronous Fluorescence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 4.2.4 Immunoassay Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 4.2.5 Postlabeling Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
4.3 Considerations for the Use of DNA Adducts in Molecular Epidemiology . . . . . . . . . . . . . . . 84 4.4 Examples of DNA Adducts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
4.4.1 DNA Adducts of Bay-Region Polycyclic Aromatic Hydrocarbons . . . . . . . . . . . . 87 4.4.2 Cyclopenta-Fused PAH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 4.4.3 Nitro-PAH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 4.4.4 DNA Adducts of Aromatic Amines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 4.4.5 DNA Adducts of Aflatoxins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 4.4.6 Small Alkyl DNA Adducts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 4.4.7 DNA Adducts of Halogenated Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 4.4.8 Endogenous Adducts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
4.5 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
“1167_C004” — #2
The formation of covalent DNA adducts by the binding of reactive metabolites of chemical carcinogens to cellular DNA represents a key early event in the cascade of molecular alterations that leads to the transformation of a normal cell into a cancer cell. The specific structures of the adducts formed and the extent of adduction induced are key determinants of the relative potencies of many chemical carcinogens. This has led to much research to understand the biological processes leading to the formation and repair of DNA adducts, and to utilizing DNA adducts as biomarkers for both exposure and effect. This chapter introduces methodologies that have been developed for the detection and measurement of DNA adducts and the application of such measurements to molecular epidemiology. A brief survey of the types of DNA adducts induced by a variety of chemical carcinogens is also included.
