INDUCTION OF UDP-GLYCOSYLTRANSFERASE-FAMILY-1 GENES IN RAT-LIVER - DIFFERENT PATTERNS OF MESSENGER-RNA EXPRESSION WITH 2 INDUCERS, 3-METHYLCHOLANTHRENE AND BETA-NAPHTHOFLAVONE

Uridine diphosphate (UDP)-glucuronosyltransferases (UGTs), presently c alled UDP-glycosyltransferases, catalyse the detoxification of many to xic and carcinogenic compounds. Glucuronidation is also a major metabo lic pathway for numerous drugs. The UGT1A6 gene (formerly known as UGT 106 and UGT1A1) has been suggested to belong to the aryl hydrocarbon (Ah) gene battery, which consists of several genes encoding for drug m etabolising enzymes regulated by dioxin and other ligands of the Ah re ceptor. In this study, we analysed the localisation of UGT1A6 expressi on in rat liver by in situ hybridisation to mRNA. Two different RNA pr obes were used, one which was specific to UGT1A6 and the other against the C terminal sequence shared by all UGT1 genes. In this study, no U GT1A6 mRNA was detected in the control animals. However, other gene(s) of the UGT1 family were expressed in the perivenous region surroundin g the central veins as detected by hybridisation with the probe agains t the common region of the UGT1 genes. Treatment with the lower dose ( 5 mg/kg) of 3-methylcholanthrene (3MC) induced expression of UGT1A6 pe rivenously. Treatment with the higher dose (25 mg/kg) of 3-Methylchola nthrene resulted in a more panacinar expression pattern. In contrast t o the perivenous induction observed with 3-methylcholanthrene, treatme nt with 15 mg/kg of beta-naphthoflavone (BNF) resulted in strong induc tion in the periportal region. The results reveal an inducer-specific pattern of UGT1A6 expression similar to that demonstrated earlier for other Ah battery genes, namely CYP1A1, CYP1A2, GSTY alpha and ALDH3. T he finding further supports the notion that common factors regulate th e regional hepatic expression of Ah battery genes. (C) 1998 Elsevier S cience Inc.