TISSUE-SPECIFIC 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN-INDUCIBLE EXPRESSION OF HUMAN UDP-GLUCURONOSYLTRANSFERASE UGT1A6

Tissue-specific expression of human UGT1A6, a UDP-glucuronosyltransfer ase isoform conjugating a wide variety of planar phenols, has been stu died using a reverse transcriptase-polymerase chain reaction, Use of i ntron-overlapping forward and reverse primers from exon 1 and 2 and of a ''hot start'' modification led to selective amplification of a UGT1 A6 mRNA fragment. In addition, homologous competitor mRNA was synthesi zed, reverse transcribed, and coamplified to allow quantitation of UGT 1A6 mRNA. Using these methods UGT1A6 mRNA could be demonstrated in liv er, kidney, duodenum, and lung, Cell-specific regulation of UGT1A6 by TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) was studied in various cell systems. TCDD induction was found in the human colon carcinoma cell l ine Caco-2 and in hepatocyte primary cultures. In contrast, in lung ca rcinoma A549 cells this isoform was constitutively expressed and not i nduced by TCDD. (C) 1996 Academic Press, Inc.