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.