Induction of UDP-glycosyltransferase family 1 genes in rat liver: different patterns of mRNA expression with two inducers, 3-methylcholanthrene and beta-naphthoflavone.
Uridine diphosphate (UDP)-glucuronosyltransferases (UGTs), presently called UDP-glycosyltransferases, catalyse the detoxification of many toxic and carcinogenic compounds. Glucuronidation is also a major metabolic pathway for numerous drugs. The UGT1A6 gene (formerly known as UGT1*06 and UGT1A1) has been suggested to belong to the aryl hydrocarbon (Ah) gene battery, which consists of several genes encoding for drug-metabolising enzymes regulated by dioxin and other ligands of the Ah receptor. In this study, we analysed the localisation of UGT1A6 expression in rat liver by in situ hybridisation to mRNA. Two different RNA probes 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 UGT1A6 mRNA was detected in the control animals. However, other gene(s) of the UGT1 family were expressed in the perivenous region surrounding the central veins as detected by hybridisation with the probe against the common region of the UGT1 genes. Treatment with the lower dose (5 mg/kg) of 3-methylcholanthrene (3MC) induced expression of UGT1A6 perivenously. Treatment with the higher dose (25 mg/kg) of 3-Methylcholanthrene resulted in a more panacinar expression pattern. In contrast to the perivenous induction observed with 3-methylcholanthrene, treatment with 15 mg/kg of beta-naphthoflavone (BNF) resulted in strong induction 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, GSTYalpha and ALDH3. The finding further supports the notion that common factors regulate the regional hepatic expression of Ah battery genes.
Saarikoski
S T
ST
Finnish Institute of Occupational Health, Department of Industrial Hygiene and Toxicology, Helsinki.
Ikonen
T S
TS
Oinonen
T
T
Lindros
K O
KO
Ulmanen
I
I
Husgafvel-Pursiainen
K
K
D000818:Animals; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D014453:Glucuronosyltransferase / Q000235:genetics*; D017403:In Situ Hybridization; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D005810:Multigene Family; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D019324:beta-Naphthoflavone / Q000494:pharmacology*
D012333:RNA, Messenger; D008748:Methylcholanthrene; D019324:beta-Naphthoflavone; D014453:Glucuronosyltransferase