ABSTRACT
Variations in absorption, distribution, metabolism, DNA repair, and cell turnover processes can modify the risk for adverse effects and the levels of biomarkers after exposure to toxic agents. This chapter considers the metabolic and DNA repair variations for their importance in detecting the impact of genotype on biological indicators of genotoxic risk and on adverse drug side-effects. That genetic constitution influences an individual’s sensitivity towards exogenous substances was first observed in cases of pharmacological treatment. Xenobiotic metabolism in humans occurs in two distinct phases; phase I, or activation, creates a reactive center in the molecule while phase II, or detoxification, is responsible for the conjugation reactions involving the incorporation of a moiety, mostly glutathione or glucuronic acid, into the molecule. The chapter presents the methods for evaluating exposure and/or biological effects to genotoxic compounds. Genetic screening may allow to estimate the risk associated with exposure to genotoxicants, and may be used as part of routine health surveillance.
