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Turnover of 3'-Polyadenylate-containing RNA in Livers from Aged, Partially Hepatectomized, Neonatal, and Morris 5123C Hepatoma-bearing Rats¹

McArdle Laboratory for Cancer Research, The Medical School, University of Wisconsin, Madison, Wisconsin 53706

The half-lives for the turnover of polysomal 3'-polyadenylate-containing RNA's [poly(A)RNA's] were determined in the following differentiated rat liver systems: 24-hr regenerating liver; liver from 30-month-old and 9-day-old rats; and the Morris 5123C hepatoma as well as its corresponding host liver. In order to allow comparisons of animals in similar physiological states, animals were adapted to 8 + 40-hr controlled feeding cycles (8 hr feeding at the start of the dark period followed by 40 hr starvation, with alternating controlled lighting for 12 hr) for 2 to 4 weeks prior to each experiment. RNA was labeled in vivo by exposure to [5-³H]orotate. The decay in specific activity of the poly(A)RNA's over consecutive 8 + 40-hr controlled feeding cycles was observed, and the data were used to calculate the half-lives of decay of poly(A)RNA. The observed poly(A)RNA half-lives were corrected for the overestimations caused by labeled precursor reutilization. The corrected poly(A)RNA half-lives were found to vary from 20 to 4 hr.

Of the three strains of rats used in these experiments, the two inbred strains, Buffalo and Fischer 344, exhibited corrected poly(A)RNA half-lives which were only 20 to 25% of those exhibited by normal adult outbred Holtzman rats. Both neonatal and regenerating liver from Holtzman rats exhibited a more rapid turnover of their contained poly(A)RNA's than was observed in normal adult rat livers of the same strain. The half-lives of the poly(A)RNA's contained in the host liver and the Morris 5123C hepatoma in Buffalo rats were not significantly different from those observed in the normal adult rat liver of the same strain. Thirty-month-old Fischer 344 rats exhibited a 4- to 5-fold increase in the corrected hepatic poly(A)RNA half-lives as compared with normal 2- to 4-month-old adult rats of the same strain. We conclude that the parameters governing poly(A)RNA turnover are flexible and can vary as a function of the state of differentiation and strain of the rat liver.

¹ This work was supported by Grant CA-07175 from the National Cancer Institute.

² Trainee in Oncology of the National Cancer Institute (T01-CA-5002). This work was performed in partial fulfillment of the requirements for the Ph.D. degree.

³ To whom requests for reprints should be addressed.

Received 9/17/79. Accepted 1/29/80.