Effects of 5-azacytidine and methyl-group deficiency on NAD(P)H: quinone oxidoreductase and glutathione S-transferase in liver.
Treatment with 5-azacytidine or dietary methyl-group deficiency effected DNA hypomethylation in mouse liver. With these treatments, NAD(P)H: quinone oxidoreductase (EC 1.6.99.2) and some glutathione S-transferase (EC 2.5.1.18) activities were over-expressed, lactate dehydrogenase (EC 1.1.1.27) activity was unaffected and the level of cytochrome P-450 was decreased. The 5-azacytidine induction of NAD(P)H: quinone oxidoreductase was significantly suppressed by puromycin, suggesting that increased enzyme activity results from an elevated level of enzyme-protein synthesis. Regulation at the transcriptional level was revealed by a substantial increase in mRNA of NAD(P)H: quinone oxidoreductase, as shown by Northern-blot analysis. The enzyme pattern observed with 5-azacytidine and with the (carcinogenic) dietary methyl-group deficiency resembles that found in hepatic nodules.
Wagner
G
G
Institut für Physiologische Chemie I, Universität Düsseldorf, Federal Republic of Germany.
Pott
U
U
Bruckschen
M
M
Sies
H
H
D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D002796:Choline Deficiency / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D004790:Enzyme Induction / Q000187:drug effects; D005982:Glutathione Transferase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008715:Methionine / Q000172:deficiency*; D008745:Methylation; D051379:Mice; D008815:Mice, Inbred Strains; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D012333:RNA, Messenger; D004247:DNA; D008715:Methionine; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; D005982:Glutathione Transferase; D001374:Azacitidine