Methods for testing compounds for DNA adduct formation

This article, based on a presentation on DNA adduct detection given at a Ge netic Toxicology Association workshop, is an overview of methods used for t esting compounds for DNA adduct formation. A DNA adduct study may be initia ted on a case by case basis when there are conflicting results within the s tandard battery of genetic toxicology tests or when tumors are detected in the animal bioassay for nongenotoxic compounds. Methods for adduct detectio n include the P-32-postlabeling assay, the use of radioactive test chemical s, physicochemical methods, and immunoassays. Of these, the P-32-postlabeli ng assay and the use of radiochemicals are discussed in greater detail, sin ce only these two methods are readily applicable to test a compound for the formation of uncharacterized DNA adducts, The other methods are applicable to those adducts that have been chemically characterized or that contain a fluorophore or electrochemically active groups. Evaluation of mutagenic an d carcinogenic risk from DNA adducts mould require the understanding of var ious parameters, including the chemical nature, quantity and stability of a dducts, proliferation rates for target cells to fix adducts into mutations, mutagenic and repair efficiencies of adducts, and the extent of modificati ons in critical genes. Since such data cannot be readily obtainable, the to xicological risk from uncharacterized adducts is difficult to assess. (C) 2 000 Academic Press.