Speaker: Larry Phillips, Developmental Therapeutics Program, National Cancer Institute, Frederick, MD

Topic: N-Acetylation of Xenobiotics - A Little History and Some Examples

Place: Building 426, Conference Room, NCI-Frederick, Frederick, MD

Time: Tuesday, December 21, 1999, at 1:30 PM

Abstract: In vivo N-acetylation was first recognized by Cohn in 1893 when he was able to isolate and identify 3-acetamidobenzoic acid from the urine of a rabbit subsequent to oral administration of 3-nitrobenzaldehyde¹. An awareness began to evolve shortly thereafter that significant differences in N-acetylation activity exists between species². This has led to the elucidation of the importance of intraspecies polymorphism in genes for drug-metabolizing enzymes (including N-acetyltransferases)³. N-Acetylation is now found to be a common metabolic transformation of xenobiotics and is designated a phase II metabolic pathway⁴. An overview of the metabolic transformations of xenobiotics with emphasis and examples of N-acetylation will be presented.

1. R. Cohn, Z. Physiol. Chem. 17, 274 (1893).
2. J. B. Muenzen, L. R. Cerecedo, and C. P. Sherwin, J. Biol. Chem. 67, 469 (1926).
3. A. V. Boddy and M. J. Ratain, Clin. Cancer. Res. 3, 1025 (1997). Review.
4. J. Chamberlain, The Analysis of Drugs in Biological Fluids (2^nd Edition). CRC Press, Boca Raton (1995).