Differences in induction by xenobiotics in murine tissues and the Hepa1c1c7 cell line of mRNAs encoding glutathione transferase, quinone reductase, and CYP1A P450s.
Levels of mRNAs encoding class-alpha glutathione transferases, class-mu glutathione transferases, quinone reductase, and cytochrome P450 1A were measured after xenobiotic induction in murine tissues and in the Hepa1c1c7 murine hepatoma cell line. RNA levels in liver and intestinal mucosa were determined after induction with phenobarbital, butylated hydroxyanisole, beta-naphthoflavone, isosafrole, or combinations of these compounds. The tissue culture cells were presented with combinations of butylated hydroxyanisole, tert-butyl-hydroquinone, and beta-naphthoflavone. In murine liver and intestinal mucosa, the greatest induction (5-15-fold) of glutathione transferases and quinone reductase was seen with butylated hydroxyanisole. Administration of phenobarbital or beta-naphthoflavone has only a modest effect (2-3-fold). In contrast, cytochrome P450 1A mRNA levels increase only slightly after BHA induction but are induced dramatically by beta-naphthoflavone. The pattern of induction is different in Hepa1c1c7 cells; there the greatest induction of all mRNAs occurred with beta-naphthoflavone. Administration of antioxidants with other xenobiotics increases mRNA levels only slightly over the levels obtained with BHA in murine tissues, or with beta-naphthoflavone in Hepa1c1c7 cells. mGSTM1 (GT8.7, Yb1), the most abundant glutathione transferase mRNA in murine liver, is also the most abundant glutathione transferase mRNA in both normal and induced Hepa1c1c7 cells. Our results suggest that BHA induction in murine liver and intestinal mucosa of class-mu and class-alpha glutathione transferases may involve regulatory elements and mediators that function poorly in Hepa1c1c7 cells.
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Department of Biochemistry, University of Virginia, Charlottesville 22908.
Pearson
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D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction; D005260:Female; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000235:genetics; D007413:Intestinal Mucosa / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis* / Q000235:genetics; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D010634:Phenobarbital / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015262:Xenobiotics / Q000494:pharmacology*; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D012333:RNA, Messenger; D015262:Xenobiotics; D002083:Butylated Hydroxyanisole; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase; D010634:Phenobarbital