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Regulation of glutathione transferase and dt diaphorase ec messenger rna species in persistent hepatocyte nodules during chemical hepatocarcinogenesis

, : Regulation of glutathione transferase and dt diaphorase ec messenger rna species in persistent hepatocyte nodules during chemical hepatocarcinogenesis. Proceedings of the National Academy of Sciences of the United States of America 81(16): 5091-5095

c[complementary]DNA probes and in vitro translation analysis were utilized to quantitate the levels of rat liver glutathione transferase (glutathione S-aralkyltransferase; RX:glutathione R-transferase, EC and DT-diaphorase [NAD(P)H:quinone-acceptor oxidoreductase, EC] mRNA in persistent hepatocyte nodules included by chemical carcinogens. Within the nodules, glutathione transferase mRNA specific for the Ya/Yc and Yb subunits are increased 3- to 5-fold, respectively, over the levels observed in normal liver or in the liver tissue surrounding the nodules. The level of DT-diaphorase mRNA is increased 5-7-fold within the nodules as compared to surrounding liver tissue or normal liver. When animals were administered 3-methylcholanthrene, a typical inducer of these mRNA 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. During chemically induced neoplastic transformation, the mRNA levels for the Yb subunit of glutathione transferase and DT-diaphorase are evidently increased in the nodules but still retain the capacity to be regulated by 3-methylcholanthrene. Although the glutathione transferase Ya/Yc mRNA are also increased in the nodules, they lost their ability to be regulated by 3-methylcholanthrene. Within the nodules there may be a specific defect in the regulatory mechanisms(s) that leads to an induction of the Ya/Yc mRNA in normal tissue by xenobiotics.

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