Accelerator mass spectrometry (AMS) is currently one of the most sensitive methods available for the trace detection of DNA adducts and is particularly valuable for measuring adducts in humans or animal models. However, the standard approach requires administration of a radiolabeled compound. As an alternative, we have developed a preliminary {sup 14}C-postlabeling assay for detection of the highly mutagenic O{sup 6}-MedG, by AMS. Procedures were developed for derivatizing O{sup 6}-MedG using unlabeled acetic anhydride. Using conventional LC-MS analysis, the limit of detection for the major product, triacetylated O{sup 6}-MedG, was 10 fmoles. On reaction with {sup 14}C-acetic anhydride, using a specially designed enclosed system, the predominant product was {sup 14}C-di-acetyl O{sup 6}-MedG. This change in reaction profile was due to a modification of the reaction procedure, introduced as a necessary safety precaution. The limit of detection for {sup 14}C-diacetyl O{sup 6}-MedG by AMS was determined as 79 attomoles, {approx}18,000 fold lower than that achievable by LSC. Although the assay has so far only been carried out with labeled standards, the degree of sensitivity obtained illustrates the potential of this assay for measuring O{sup 6}-MedG levels in humans
