Application of accelerated mass spectrometry (AMS) in DNA adduct quantification and identification.

DNA adducts are nucleotide bases that have been covalently modified by reactive electrophilic chemical intermediates, and have been extensively researched for their role in mutagenesis and carcinogenesis. However, many DNA adduct measurement techniques have difficulty in the quantification of adducts at realistic human exposure levels. We are using the extremely sensitive analytical technique of accelerator mass spectrometry (AMS) to study adducts either at low dose or directly in humans. AMS is a technique for measuring isotope ratios with high selectivity, attomole sensitivity (10(-18) mol) and precision of 0.5-10%, depending on isotope level and preparation method. This sensitivity and precision is being used to study the dose-response, toxicokinetics, and toxicodynamics of DNA adduct formation and removal following administration of very low doses of chemicals.