Genetic regulation of
acetyl coenzyme A-dependent N-
acetyltransferase (
NAT)and O-
acetyltransferase (OAT) activities may play an important role in the metabolic activation of arylamine chemicals and
carcinogens. N-acetylation is thought to be the first step in arylamine metabolism. The
enzyme responsible for N-acetylation is called
NAT. In this study, synthetic non-steroidal
antiestrogen tamoxifen was selected for determining the inhibition of arylamine
NAT activity, gene expression (
NAT mRNA) and DNA-2-aminofluorene adduct formation in human
leukemia HL-60 cell line. The results demonstrated that
tamoxifen did not affect the level of
NAT mRNA in HL-60 cells. But the results also showed that
NAT activity and
2-Aminofluorene-DNA adduct formation in HL-60 cells were inhibited and decreased by
tamoxifen in a dose-dependent manner when the doses of
tamoxifen up to 100 micro M. We also examined the standard steady-state kinetic analysis, and the data showed that
tamoxifen may be an uncompetitive inhibitor to
NAT activity in cytosols based on the decrease apparent values of Km and Vmax. This report is the first finding that
tamoxifen inhibited human
leukemia HL-60 cells
NAT activity and DNA-2-aminofluorene on adduct formation.