Effect of Administering 8-Azaguanine at Various Times on Liver Enzyme Activities of Starved-Refed Rats 1

Abstract

Summary

In rats starved for 2 days and then refed a 65% glucose diet for 2 days the activities of liver glucose-6-phosphate dehydrogenase and malic enzyme reached approximately twice normal levels. This overshoot of normal activity was totally prevented if 8-azaguanine was administered 24 hr or sooner after refeeding. If the antibiotic was administered 30 hr after refeeding, the overshoot was still inhibited, although to a lesser extent, while if 8-azaguanine was administered 36 hr after refeeding, no noticeable reduction in the overshoot was noted. The results indicate that the overshoot in the starved-refed experiment requires de novo RNA synthesis and that this de novo RNA synthesis seems to occur between 24 and 36 hr after refeeding. To further check this hypothesis, the effect of 8-azaguanine was studied on the 4-day overshoot in glucose-6-phosphate dehydrogenase and malic enzyme activities. It was found that the overshoot was totally prevented by injecting the antibiotic 30 hr or sooner after refeeding. If the antibiotic was injected 48 hr after refeeding, the activities of glucose-6-phosphate dehydrogenase and malic enzyme reached about 75% of the levels in untreated rats refed for 4 days. Since, the administration of 8-azaguanine for 2 days to ad libitum-fed rats caused about an equal reduction in glucose-6-phosphate dehydrogenase activity, but not in malic enzyme activity, the results could be interpreted in one of two ways: (i) that the de novo RNA synthesis necessary for the overshoot is not entirely completed by 48 hr after refeeding, or (ii) that the above mentioned RNA synthesis is completed within 48 hr after refeeding, but that 8-azaguanine reduces the level of functional RNA by interfering with the normal turnover of RNA.