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Influence of Acetylaminofluorene, Growth Hormone, Testosterone, and Hypothyroidism on Incorporation of Uracil-2-C¹⁴ in Liver RNA in the Rat^*

( Department of Biochemistry and the Division of Endocrine and Cancer Research, Jefferson Medical College, Philadelphia, Pa.)

1. In the rat, uracil-2-C¹⁴ is actively incorporated in vivo in the nuclear and cytoplasmic ribonucleic acid (RNA) of regenerating liver, 90-day 2-acetylaminofluorene (AAF) ("preneoplastic") liver, and AAF-induced hepatoma, in contrast to its very limited utilization for this purpose in normal rat liver.

2. Under the experimental conditions employed, the RNA uridylic: cytidylic acid activity ratio remained essentially normal in regenerating liver and was relatively low in "preneoplastic" liver and hepatoma.

3. Administration of testosterone and of growth hormone resulted in increased incorporation of uracil-2-C¹⁴ in the liver RNA of normal rats. Differences were observed in the uridylic: cytidylic acid activity ratios.

4. Pretreatment with I¹³¹ almost completely inhibited the increase in uracil-2-C¹⁴ incorporation in "preneoplastic" liver, but had no effect on this process in regenerating liver. Pretreatment with thiouracil had a moderately inhibitory effect in regenerating liver.

5. In contrast to the findings in vivo, the "preneoplastic" livers of AAF-treated athyroid rats exhibited the same active in vitro incorporation of uracil-2-C¹⁴ in RNA and the same relatively low uridylic: cytidylic activity ratio as the livers of similarly treated euthyroid rats.

6. The observed differences between regenerating liver on the one hand and "preneoplastic" liver and hepatoma on the other suggest that there may be differences in the utilization of uracil for nucleic acid synthesis in these tissues that are not reflected in the total incorporation of this precursor in RNA.

^* This work was supported in part by a grant, C-1307, from the National Cancer Institute, National Institutes of Health, U.S. Public Health Service.

Received 2/ 1/58.