Metabolism of Nucleolar Ribonucleic Acid after Partial Hepatectomy.

When a large part of the liver of a mammal is removed, there follows, after a lag period,’ a dramatic increase in the number of hepatic cells making DNA. Partial hepatectomy has, for this reason, been commonly used to investigate the mechanisms that normally govern entry of a cell into the period of DNA formation. The liver appears to be informed immediately about the partial hepatectomy, and several hepatic changes, including an increase in the rate of RNA metabolism, begin at once after the operation (I). The early changes in liver RNA synthesis that follow partial hepatectomy have become of particular interest in view of the results obtained in similar studies with cultured kidney cells (2-4). With the kidney cells, control of DNA replication has been shown to depend largely on the control of RNA metabolism. Stowell (5) made volumetric measurements of liver nucleoli 24 hours after partial hepatectomy and found a 4-fold increase in their size. With microphotometric measurements of a bound basic dye, Kleinfeld (6) and Swift, Rebhun, Rasch, and Woodard (7) then showed that the enlargement of the nucleolus is accompanied by an increase in nucleolar RNA. Although their first measurements were made 14 hours after the operation, the rise appeared to begin immediately postoperatively. Later, using radioglucose, Schneider and Potter (8) found an increase, 6 hours postoperatively, in the rate of incorporation of label into hepatic RNA. More recently (l), a linear rise in the rate of incorporat’ion of I%-orotate into liver RNA was shown to begin immediat.ely after partial hepatectomy, reaching a maximum about twice the initial rate by about 6 hours. Enhancement of the synthetic rate was equally reflected in each of the subcellular fractions esamined: nuclear, mit.ochondrial, microsomal, and soluble. Of interest are the observations that were made with two inhibitors, actinomycin D and p-fluorophenylalanine. In amounts that had no effect on the normal rate of RNA synthesis, these agent’s completely and reversibly suppressed the rate increase that followed partial hepatectomy. Especially in view of the work of Swift et al. (7), it was of interest to compare the metabolic changes following soon after partial hepatectomy in liver nucleolar RNA with those of the over-all hepatic RNh. Such studies, it was hoped, might throw some light on the role of the nucleolus in the period preceding