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Alternative Pathways of Glucose Metabolism

III. The Incorporation of Radioactivity from Glucose-1-C¹⁴ into the Nucleic Acids of Regenerating Rat Liver^*

John H. Schneider and Van R. Potter

( McArdle Memorial Laboratory, University of Wisconsin, Madison 6, Wis.)

1. The rate of excretion of radioactivity following the intraperitoneal injection of 10 µc. of a-D-glucose-1-C¹⁴ into rats with 24-hour regenerating livers was examined. It was found that 83 per cent of the dose was excreted as carbon dioxide by 12 hours after the injection and that an additional 4.5 per cent was excreted in the urine. These results were higher than values previously obtained with tumor-bearing rats.

2. Rats were injected at different times after partial hepatectomy and were sacrificed 2 hours after injection. Incorporation of radioactivity during this 2-hour period was used as a measure of the degree of stimulation of the synthesis of a given type of nucleic acid.

3. Based on this criterion, it was found that stimulation for the synthesis of nuclear and cytoplasmic ribonucleic acid (RNA) increased almost immediately after the operation. In contrast, there was no stimulation for the synthesis of deoxyribonucleic acid (DNA) until 18 hours after the operation. At that time, stimulation of DNA synthesis could be detected, and it rose to a maximum by 30 hours after the operation.

4. When rats were injected 24 hours after the operation and sacrificed at different times after injection, it was found that the specific activity (S.A.) of the cytoplasmic RNA reached a maximum by 12 hours after the injection. After this time, the S.A. of the cytoplasmic and nuclear RNA were not significantly different, and the S.A. of both types of RNA decreased slowly after 12 hours postinjection, so that by 4 weeks after the injection only a small amount of radioactivity remained in these fractions. The S.A. of the DNA reached a maximum by 96 hours after the injection. By 4 weeks after the injection, the S.A. of the DNA was still at a high level. The decrease observed was attributed to dilution rather than destruction of the radioactive DNA.

5. The S.A. of the nuclear RNA rose rapidly to a maximum by 2 hours after the injection of radioactive glucose and then decreased exponentially between 2 and 6 hours after the injection. The possible significance of this exponential disappearance of radioactive nuclear RNA from the nucleus was discussed.

^* This work was supported in part by a grant (No. C-646) from the National Cancer Institute, United States Public Health Service.

National Science Foundation Fellow 1954–1955.

Received 3/12/57.