TISSUE-SPECIFIC CONSTITUTIVE AND INDUCIBLE EXPRESSION OF RAT PHENOL UDP-GLUCURONOSYLTRANSFERASE

To investigate constitutive and inducible expression of rat phenol UDP -glucuronosyltransferase (UGT1A1) in liver and extrahepatic tissues, a selective cDNA probe for its unique exon 1 was utilized. 6-Hydroxychr ysene was used as a functional probe of UGT1A1 activity. Constitutive expression of UGT1A1 was low in liver, but high in kidney, testis, epi didymis and ovary. After treatment with 2,3,7,8-tetrachlorodibenzo-p-d ioxin (TCDD; 10 mu g/kg for 7 days) the UGT1A1 mRNA level was markly i ncreased in liver (ca. 10-fold), and only moderately enhanced (up to 2 -fold) in extrahepatic tissues where constitutive enzyme expression wa s high. UGT activity toward 6-hydroxychrysene was strongly inducible i n liver (ca. 9-fold) and only moderately inducible in extrahepatic tis sues (up to 2-fold). The results suggest complex tissue-specific regul ation of UGT1A1 including positive and negative transcriptional factor s and marked inducibility by TCDD in liver.