A simple double-isotope method is described which permits precise determination of both synthetic and degradative rates of liver cell constituents during the course of regeneration after partial hepatectomy. By employing animals which have previously received both tritiated thymidine and an appropriate 14C-labeled precursor it is possible to obtain precise turnover data in individual animals by comparing the concentration and the total isotope content of the 14C-labeled component in the initially excised and regenerating portions of liver. The presence of a 3H marker in the liver DNA makes it possible in addition to calculate the exact size of the initial liver remnant and hence to interpret the observed 14C turnover data in terms of specific rates of synthesis and degradation. As an illustration of its usefulness this method has been employed to study changes in cell proliferation rate after partial hepatectomy, and to determine the day-to-day rates of synthesis and degradation of ribosomal RNA, the major component of rat liver RNA. It is shown that during the first 24 h after a 70% hepatectomy ribosomal RNA synthesis undergoes a nearly fourfold stimulation to a rate of approximately 53% per unit mass per day. This accelerated rate of synthesis is sustained for an additional 2 days and is accompanied by exponential DNA synthesis until the hepatic remnant has more than tripled its initial DNA and ribosomal RNA content to attain values identical to those in the initial intact liver; the rates of DNA and RNA synthesis then fall abruptly. In striking contrast to the marked fluctuations in its rate of synthesis, ribosomal RNA continues to be degraded throughout the course of regeneration at a constant rate of 12% per day, a rate virtually identical to that observed in normal liver. The approach described here permits the accurate determination of turnover rates over intervals considerably shorter than even one half-life, and should be applicable to the study of the specific rates of synthesis and degradation of other cell components as well.

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