Abstract
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.
- Copyright ©, 1971, by Academic Press, Inc.
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|