Abstract
In this study, paclitaxel was used to determine inhibition of arylamine N-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.
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