Sulindac inhibited gene expression and activity of arylamine N-acetyltransferase and DNA-2-aminofluorene adduct formation in T24 human bladder tumor cells.
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.
Yang
C C
CC
Department of Urology, China Medical College Hospital, Taichung, Taiwan, Republic of China.
Chung
J G
JG
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005449:Fluorenes / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D013467:Sulindac / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D001749:Urinary Bladder Neoplasms
C052668:2-aminofluorene-DNA complex; D000970:Antineoplastic Agents; D018736:DNA Adducts; D005449:Fluorenes; D012333:RNA, Messenger; D013467:Sulindac; D001191:Arylamine N-Acetyltransferase