In this study, paclitaxel was used to determine inhibition of arylamine X-acetyltransferase (NAT) activity. gene expresssion and 2-aminofluorene-DNA adduct formation in a human lung tumor cell line (A549). The activity of NAT was measured by HPLC assaying for the amounts of N-acetyl-2-aminofluorene (2-AAF) and remaining 2-aminofluorene (2-AF). Human lung tumor cell cytosols and intact cells were used for examining NAT activity and carcinogen-DNA adduct formation. The results demonstrated that NAT activity, gene expression (NAT1 mRNA) and 2-AF-DNA adduct formation in human lung tumor cells were inhibited and decreased by paclitaxel in a dose-dependent manner. The effects of paclitaxel on the values of the apparent K-m and V-max of NAT from human lung tumor cells were also determined in both examined systems. The result also indicated that paclitaxel decreased the apparent values of K-m and V-max from human lung tumor cells in both cytosol and intact cells. Thus, paclitaxel is an uncompetitive inhibitor to NAT enzyme. (C) 2002 Elsevier Science Ltd. All rights reserved.
