Regulation of glutathione transferase and DT-diaphorase mRNAs in persistent hepatocyte nodules during chemical hepatocarcinogenesis.
We have utilized cDNA probes and in vitro translation analysis to quantitate the levels of rat liver glutathione transferase (glutathione S-aralkyltransferase; RX:glutathione R-transferase, EC 2.5.1.18) and DT-diaphorase [NAD-(P)H:quinone-acceptor oxidoreductase, EC 1.6.99.2] mRNAs in persistent hepatocyte nodules induced by chemical carcinogens. Our results indicate that within the nodules, glutathione transferase mRNAs specific for the Ya/Yc and Yb subunits are increased 3-fold and 5-fold, respectively, over the levels observed in normal liver or in the liver tissue surrounding the nodules. Similarly, the level of DT-diaphorase mRNA is increased 5- to 7-fold within the nodules as compared to surrounding liver tissue or normal liver. When animals were administered 3-methylcholanthrene, a typical inducer of these mRNAs in normal animals, a further increase in the glutathione transferase Yb mRNA(s) and DT-diaphorase mRNA was observed in the nodules; however, the Ya/Yc mRNA levels remained unaffected. Our data indicate that during chemically induced neoplastic transformation, the mRNA levels for the Yb subunit of glutathione transferase and DT-diaphorase are increased in the nodules but still retain the capacity to be regulated by 3-methylcholanthrene. Although the glutathione transferase Ya/Yc mRNAs are also increased in the nodules, they lost their ability to be regulated by 3-methylcholanthrene. These latter data suggest that within the nodules there is a specific defect in the regulatory mechanism(s) that leads to an induction of the Ya/Yc mRNAs in normal tissue by xenobiotics.
D015073:2-Acetylaminofluorene; D000818:Animals; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000302:isolation & purification; D005982:Glutathione Transferase / Q000235:genetics*; D008099:Liver / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D008970:Molecular Weight; D016660:NAD(P)H Dehydrogenase (Quinone); D009247:NADH, NADPH Oxidoreductases / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D011808:Quinone Reductases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic
D012333:RNA, Messenger; D004247:DNA; D015073:2-Acetylaminofluorene; D009247:NADH, NADPH Oxidoreductases; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; D005982:Glutathione Transferase