CHARACTERIZATION AND REGULATION OF RAT LIVER UDP GLUCURONOSYLTRANSFERASES

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Abstract
1. The use of DNA recombinant techniques to study UDP glucuronosyltransferases is reviewed. 2. The cloning and sequencing of the cDNAs to five forms of UDP glucuronosyltransferase demonstrated that these proteins are encoded by a superfamily of genes. 3. The substrate specificities of four isozymes have been analysed by expression of their corresponding cDNAs in cell culture. 4. Analysis of liver mRNA levels using radiolabelled DNA probes demonstrated that one isozyme, UDPGTr-2, is elevated by phenobarbital whereas a second isozyme, 4-nitrophenol GT is elevated by 3-methylcholanthrene. The levels of other isozymes are unaffected by these two prototypic inducers of drug metabolizing enzymes. 5. The level of 4-nitrophenol GT mRNA is elevated 10-15-fold in hyperplastic nodules in livers of rats treated with 2-acetylaminofluorene. Similar increases were not observed for mRNAs encoding other forms of UDP glucuronosyltransferase.