Toxicological considerations in the application and interpretation of DNA adducts in epidemiological studies.

This chapter will review a variety of issues related to the use of biomarkers in molecular epidemiological studies. It will draw upon experience gained from related mechanistic research in toxicological studies. This includes important methodological issues that impact on the type of assays that can be used and how these issues affect the selection of the method and the biological sample. It will also address issues affecting the use of biomarkers as measures of exposure and effect, and discuss inferences for causality and the selection of target organ versus surrogate tissues. Combining information from toxicological studies can also aid in the interpretation of epidemiological studies, such as tissues with and without strong biological plausibility and relationships between observed DNA adducts and those that arise from endogenous processes. Finally, it will discuss issues related to important pathways of metabolism and implications of genetic polymorphisms. These critical issues affect both the design and interpretation of molecular epidemiological studies.