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Paclitaxel (Taxol) Inhibits the Arylamine N‐Acetyltransferase Activity and Gene Expression (mRNA NAT1) and 2‐Aminofluorene‐DNA Adduct Formation in Human Bladder Carcinoma Cells (T24 and TSGH 8301)
Author(s) -
Yang ChingChiang,
Chen GuangWei,
Lu HsuehFu,
Wang DerYuan,
Chen YiShuan,
Chung JingGung
Publication year - 2003
Publication title -
pharmacology & toxicology
Language(s) - English
Resource type - Journals
eISSN - 1600-0773
pISSN - 0901-9928
DOI - 10.1034/j.1600-0773.2003.920606.x
Subject(s) - paclitaxel , gene , messenger rna , dna , gene expression , cancer research , arylamine n acetyltransferase , adduct , microbiology and biotechnology , n acetyltransferase , acetyltransferase , biology , carcinoma , chemistry , chemotherapy , genetics , acetylation , organic chemistry
Acetylator polymorphism in man results from differential expression of human liver N‐acetyltransferase. N‐Acetyltransferase enzyme activity has been demonstrated to be involved in some types of chemical carcinogenesis. Paclitaxel (taxol) had been shown to affect N‐acetyltransferase activity of human lung cancer cells. In this study, paclitaxel was chosen to investigate the effects of arylamine N‐acetyltransferase activity (N‐acetylation of substrate), gene expresssion and 2‐aminofluorene‐DNA adduct formation in human bladder carcinoma cell lines (T24 and TSGH 8301). The N‐acetyltrasnsferase activity (N‐acetylation of substrates) was determined by high performance liquid chromatography assaying for the amounts of acetylated 2‐aminofluorene and p ‐aminobenzoic acid and nonacetylated 2‐aminofluorene and p ‐aminobenzoic acid. Intact human bladder carcinoma T24 and TSGH 8301 cells were used for examining N‐acetyltransferase activity, gene expression and 2‐aminofluorene‐DNA adduct formation. The results demonstrated that the N‐acetyltransferase activity, gene expression (NAT1 mRNA) and 2‐aminofluorene‐DNA adduct formation in intact human bladder carcinoma cells were inhibited and decreased by paclitaxel in a dose‐dependent manner. The effects of paclitaxel on the apparent values of Km and Vmax of N‐acetyltransferase enzyme from intact human bladder carcinoma cells were also determined in these cell lines. A marked influence of paclitaxel was observed on the decreasing apparent values of K m and V max from intact human bladder carcinoma cells (T24 and TSGH 8301). Thus, paclitaxel is an uncompetitive inhibitor to the NAT enzyme.

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