TY - JOUR T1 - Acetylation of the Carcinogen <em>N</em>-Hydroxy-2-acetylaminofluorene by Acetyl Coenzyme A to Form a Reactive Ester JF - Molecular Pharmacology JO - Mol Pharmacol SP - 381 LP - 388 VL - 7 IS - 4 AU - PRABHAKAR D. LOTLIKAR AU - LEIDA LUHA Y1 - 1971/07/01 UR - http://molpharm.aspetjournals.org/content/7/4/381.abstract N2 - Nonenzymatic acetylation of various carcinogenic hydroxamic acids was studied with acetyl-1-14C-CoA as the acetyl donor. Formation of acetate esters was studied by determination of the benzene-extractable radioactivity. Interaction of these esters in vitro at pH 7.5 with methionine and guanosine was used as a measure of their reactivity. N-Hydroxy-2-acetylaminofluorene was acetylated to a much greater extent than 2-aminofluorene, 2-acetylaminofluorene, or its ring-hydroxylated derivatives. The reaction was dependent on pH and the type of buffer, period of incubation, and the concentrations of acetyl-CoA and N-hydroxy-2-acetylaminofluorene. With 5 min of incubation and KHCO3-KOH buffer, the pH optimum was found to be 10. On the basis of its ultraviolet absorption spectrum, RF value after paper chromatography, lability to alkali, and characteristic reaction products with methionine and guanosine, the acetylated reaction product of N-hydroxy-2-acetylaminofluorene has been characterized as N-acetoxy-2-acetylaminofluorene. Among various N-hydroxy derivatives tested, N-hydroxyurethane and its N-methyl derivatives were acetylated most rapidly. It is suggested that acetate esters of hydroxamic acids may also be some of the ultimate carcinogenic metabolites of carcinogenic hydroxamic acids. ER -