BIOMAT Database Logo BIOMAT Database Logo

Identification of a rat oltipraz-inducible UDP-glucuronosyltransferase (UGT1A7) with activity towards benzo(a)pyrene-7,8-dihydrodiol. 1997

A D Grove, and F K Kessler, and R P Metz, and J K Ritter
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA.

Previous work has shown that polycyclic aromatic hydrocarbons and oltipraz both induce an unidentified rat liver UDP-glucuronosyltransferase with activity toward benzo(a)pyrene-7, 8-diol, the proximate carcinogenic form of benzo(a)pyrene. Here we report the isolation of a benzo(a)pyrene-7,8-diol transferase-encoding cDNA, LC14, from an adult rat hepatocyte-derived cell line (RALA255-10G LCS-3). The predicted amino acid sequence of LC14 is nearly identical (5 differences out of 531 residues) to that deduced from UGT1A7, recently cloned at the genomic DNA level (Emi, Y., Ikushiro, S., and Kyanagi, T. (1995) J. Biochem. (Tokyo) 117, 392-399). Northern analysis of RNA from female F344 rat liver and LCS-3 cells revealed over a 40-fold and 4.4-fold enhancement by oltipraz treatment, respectively. Benzo(a)pyrene-7, 8-diol glucuronidating activity was detected (0.4 nmol/10(6) cells/16 h) in AHH-1 cells transfected with the LC14 expression vector, pMF6-LC14-3. The LC14-encoded transferase exhibited even higher activity toward certain benzo(a)pyrene phenols, including the major 3- and 9-phenol metabolites (4.1 and 2.8 nmol/10(6) cells/16 h, respectively). The Km of the enzyme for (-)-trans benzo(a)pyrene-7, 8-diol and 3-OH-BP was 15.5 and 12.3 microM, respectively. Northern analyses of total RNA revealed expression of LC14 or LC14-like RNA in all extrahepatic tissues tested. Marked inducibility by oltipraz was observed only in liver and (to a lesser extent) intestine. The results suggest that induction of UGT1A7 may explain the increased glucuronidating activities toward benzo(a)pyrene-7,8-diol and other metabolites that occur following treatment with polycyclic aromatic hydrocarbon-type inducing agents and oltipraz. UGT1A7 appears to represent an important cellular chemoprotective enzyme which mediates conjugation and elimination of toxic benzo(a)pyrene metabolites.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011719 Pyrazines A heterocyclic aromatic organic compound with the chemical formula C4H4N2. Pyrazine
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004101 Dihydroxydihydrobenzopyrenes Benzopyrenes saturated in any two adjacent positions and substituted with two hydroxyl groups in any position. The majority of these compounds have carcinogenic or mutagenic activity. Benzopyrene Dihydrodiols,Dihydrobenzopyrene Diols,Dihydrodiolbenzopyrenes,Dihydrodiols, Benzopyrene,Diols, Dihydrobenzopyrene
D004790 Enzyme Induction An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. Induction, Enzyme
D005260 Female Females
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001483 Base Sequence The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence. DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA

Related Publications

A D Grove, and F K Kessler, and R P Metz, and J K Ritter
Induction of a rat liver benzo[a]pyrene-trans-7,8-dihydrodiol glucuronidating activity by oltipraz and beta-naphthoflavone.
January 1997, Carcinogenesis,
A D Grove, and F K Kessler, and R P Metz, and J K Ritter
Characterization of benzo(a)pyrene-trans-7,8-dihydrodiol glucuronidation by human tissue microsomes and overexpressed UDP-glucuronosyltransferase enzymes.
April 2002, Cancer research,
A D Grove, and F K Kessler, and R P Metz, and J K Ritter
Glutathione conjugation of benzo[a]pyrene-7,8-dihydrodiol and benzo[a]pyrene-7,8-dihydrodiol-9,10-oxide in the perfused rat liver.
January 1983, Chemico-biological interactions,
A D Grove, and F K Kessler, and R P Metz, and J K Ritter
Inhibition of benzo(a)pyrene and benzo(a)pyrene 7,8-dihydrodiol metabolism by benzo(a)pyrene quinones.
October 1979, Cancer research,
A D Grove, and F K Kessler, and R P Metz, and J K Ritter
Metabolism of benzo[a]pyrene-7,8-dihydrodiol and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide to protein-binding products and glutathione conjugates in isolated rat hepatocytes.
August 1984, Carcinogenesis,
A D Grove, and F K Kessler, and R P Metz, and J K Ritter
Lipoxygenase-catalyzed epoxidation of benzo(a)pyrene-7,8-dihydrodiol.
March 1989, Biochemical and biophysical research communications,
A D Grove, and F K Kessler, and R P Metz, and J K Ritter
Linoleate-dependent co-oxygenation of benzo(a)pyrene and benzo(a)pyrene-7,8-dihydrodiol by rat cytosolic lipoxygenase.
May 1992, Xenobiotica; the fate of foreign compounds in biological systems,
A D Grove, and F K Kessler, and R P Metz, and J K Ritter
Chinese medicinal herbs modulate mutagenesis, DNA binding and metabolism of benzo[a]pyrene 7,8-dihydrodiol and benzo[a]pyrene 7,8-dihydrodiol-9,10-epoxide.
February 1992, Cancer letters,
A D Grove, and F K Kessler, and R P Metz, and J K Ritter
The role of the Ah receptor and p38 in benzo[a]pyrene-7,8-dihydrodiol and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-induced apoptosis.
May 2003, The Journal of biological chemistry,
A D Grove, and F K Kessler, and R P Metz, and J K Ritter
Benzo[a]pyrene 7,8-dihydrodiol is more carcinogenic than benzo[a]pyrene in newborn mice.
March 1977, Nature,
Copied contents to your clipboard!