Sulindac inhibited gene expression and activity of arylamine N-acetyltransferase and DNA-2-aminofluorene adduct formation in T24 human bladder tumor cells.

Abstract

We demonstrated in vivo that non-steroidal anti-inflammatory drugs including sulindac can act as inhibitors of urinary bladder carcinogenesis in rats. The aim of the present study was to determine whether sulindac affects arylamine N-acetyltransferase (NAT) activity and gene expression and DNA-2-aminofluorene adduct formation in the T24 human bladder tumor cell line. The NAT activity (N-acetylation of 2-aminofluorene) was measured by high performance liquid chromatography assaying for the amount of acetylated 2-aminofluorene and the remaining 2-aminofluorene (AF). The results demonstrated that NAT activity in T24 cells were inhibited by the sulindac in a dose-dependent manner. The apparent values of Km and Vmax of NAT from T24 cells were also decreased by sulindac. This inhibition was not competitive. The amount of DNA-AF adduct formation in T24 cells was also inhibited by sulindac. The data also demonstrated that sulindac inhibited the NAT mRNA level in T24 cells.