Pyrimidine metabolism. IV. A comparison of normal and regenerating rat liver.

It has been shown that uracil can be incorporated into ribonucleic acid of the normal rat tissues (2). However, this incorporation becomes significant only when the enzymes associated with the catabolism of uracil are saturated with their substrates. When thii is achieved, the incorporation of uracil into RNA increases with substrate concentration. At high concentrations the extent of incorporation of uracil, uridine, uridylic acid, and of erotic acid into RNA becomes of the same order of magnitude. These experiments showed further that an inverse relationship exists between the capacity of a tissue to synthesize RNA and its capacity to degrade uracil. A group of normal, nondividing tissues (rat and mouse liver) has been shown to have a high catabolic capacity for uracil and a low capacity to incorporate uracil into RNA. In contrast, a group of normal but rapidly dividing tissues (intestinal mucosa, regenerating rat liver) and also a group of abnormal tissues (hepatomas (2) as well as Ehrlich ascites cells (3)) have a low capacity for the degradation of uracil, whereas they actively incorporate this pyrimidine into RNA. An interplay between the degradative and the synthetic pathways for uracil could constitute an important means for the control of RNA synthesis. From a consideration of these facts the possible existence of a cellular homeostatic mechanism involved in the regulation of RNA synthesis was proposed (2). In order to explore further the details of such a homeostatic mechanism we have studied the changes which occur in the anabolic and catabolic capacities of enzymes involved in nucleic acid metabolism. The aim has been to contrast these capacities in normal rat liver with those occurring in rat liver during the course of regeneration induced by partial hepatectomy. Variations in the catabolic and anabolic rates could then be considered to reflect changes in the state of growth in cell types of like origin. The results of these experiments give additional support to the contention that a homeostatic mechanism exists for the control of RNA synthesis. Evidence will also be presented which indicates that similar mechanisms may control the metabolism of thymine as well as that of thymidine 5’-phosphate and consequently exert an effect on DNA synthesis. Based on the results of this and previous work we wish to suggest that a transition from a high catabolic-low anabolic capacity to the inverse situa-