Measurement of a malondialdehyde-DNA adduct

Abstract

Determining the levels of various DNA adducts has become an essential tool in understanding the toxicology of carcinogens. Direct measurement of DNA adduct levels, the true biologically effective dose of a mutagen, can be correlated with biological outcomes or used to probe mechanisms of adduct formation. Each adduct to be measured requires a specific assay. Malondialdehyde is a carcinogenic and mutagenic electrophile that is endogenously produced during peroxidation of polyunsaturated fatty acids. Its reaction with deoxyguanosine produces a fluorescent exocyclic pyrimidopurinone that can be detected by gas chromatographic/negative chemical ionization-electron capture mass spectroscopy. Methods for preparing an immunoaffinity gel and for HPLC quantification of nucleosides are also included.