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Nucleic Acid Metabolism in Regenerating Rat Liver

II. Studies on Growing Rats^*

Yasuyuki Takagi, Liselotte I. Hecht and Van R. Potter

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

The experiments described demonstrated that in the young, growing rat orotic acid-6-C¹⁴ was converted to DNA pyrimidines for 24 hours following the initial injection, and the radioactivity was retained in the DNA during the next 7 weeks, a period during which the liver weight increased about threefold.

Partial hepatectomy 40 or 46 days after administration of orotic acid-6-C¹⁴ to the young rats resulted in essentially no change in the radioactivity content of the DNA during a 5- or 21-day period of liver regeneration in 3 out of 4 animals. These data support the proposed concept of the relatively high biochemical stability of DNA and show that this is true in tissues with widely varying rates of mitotic activity.

When partial hepatectomy was performed on growing or adult rats at sufficiently short intervals after administration of orotic acid-6-C¹⁴, a radioactive intermediate was mobilized which served as a precursor pool from which labeled DNA pyrimidine nucleotides were synthesized. After the initial lag period which followed the operation, an increase in the C¹⁴ content of the DNA was observed. The radioactivity level in the acid-soluble fraction and in the nuclear RNA fraction decreased extensively during the first 13-hour interval, but during the period of DNA synthesis the C¹⁴ content of these fractions remained constant. The total radioactivity in the cytoplasmic RNA fraction was more than adequate to account for the maintenance of the radioactivity in the acid-soluble fraction, which presumably provides the immediate precursors for the synthesis of DNA and RNA.

^* This work was supported by a grant (No. C-646) from the National Cancer Institute, National Institutes of Health, United States Public Health Service. A preliminary report of this work was given previously (16).

Present address, Department of Biochemistry, Osaka Dental College, Osaka, Japan.

Received 7/16/56.