Nucleic acid metabolism in regenerating rat liver. I. The rate of deoxyribonucleic acid synthesis in vivo.

An ideal system for examining the relationship between ribonucleic acid (UNA) and deoxyribonucleic acid (DNA) metabolism in animals would be a tissue where synchronous cell division occurs. Isotopie tracer studies (9, 22, 25) and determina tion of the DNA content per nucleus in the liver cells of partially hepatectomized rats (25, 26, 83) have suggested that in animals the most feasible approach to this situation is by the use of re generating liver. The observations that incorpora tion of isotopically labeled precursors into DNA is correlated with the occurrence of cell division (5,17,30) and that isotopes are retained extensive ly in the DNA of mitotically inactive and active cells (2, 4, 6,10-12,16, 31, 32) indicate that DNA displays a high biochemical stability. Therefore, it is assumed that the extent of the incorporation of natural precursors into DNA can be taken as a measure of the rate of DNA synthesis. This is supported by the reasonable agreement between the incorporation of P32into DNA and the quan titative increase of DNA that has been demon strated in regenerating liver (25). In the present report the rates of DNA synthesis during the early period of liver regeneration, as studied with orotic acid-6-C14in vivo,are described in detail to provide a time schedule for studies of the nucleic acid metabolism in a tissue which is changing its metabolism to meet the synthetic and energy re quirements of cell division. Orotic acid, a precursor with relatively few alternative metabolic pathways, is extensively converted to the acid-soluble uracil and cytosine ribonucleotides (21) and the pyrimidine nucleotides of UNA (20, 27, 35) in normal liver. In re generating liver it has been demonstrated that orotic acid also serves as a precursor for the pyrimidine nucleotides of DNA (27, 34).