GLUCURONIDATION IN THE CACO-2 HUMAN INTESTINAL-CELL LINE - INDUCTION OF UDP-GLUCURONOSYLTRANSFERASE 1-ASTERISK-6

The ability of the differentiated human intestinal cell line, Caco-2, to glucuronidate various endobiotic and xenobiotic molecules was inves tigated. Glucuronidation of hydroxylated or carboxylic acid compounds such as 1-naphthol, thymol, androsterone, estriol, hyodeoxycholic acid , lithocholic acid, chloramphenicol, paracetamol and morphine could be determined in microsomal fractions of Caco-2 cells. The activity towa rd 1-naphthol was the highest glucuronidation activity measured in Cac o-2 cells. This activity was specifically increased four-fold upon add ition of beta-naphthoflavone into culture medium but not by rifampicin e or clofibrate and was related to a biosynthesis of UDP-glucuronosylt ransferase 16 (UGT1*6). alpha-Naphthoflavone did not affect the induc ing property of beta-naphthoflavone. 7-Ethoxyresorufin-O-dealkylation activity, supported by cytochrome P4501A1, was induced more than 1000- times in Caco-2 cells by beta-naphthoflavone treatment, and this effec t was partially abolished by alpha-naphthoflavone treatment. The resul ts suggest that several isoforms, including UGT16, are expressed in C aco-2 cells.