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[Cancer Research 24, 509-512, April 1, 1964]
© 1964 American Association for Cancer Research

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The Influence of Age upon the Incorporation of Thymidine-2-C14 into the DNA of Regenerating Rat Liver*

Nancy L. R. Bucher, Miriam N. Swaffield and Joseph F. DiTroia{dagger}

( John Collins Warren Laboratories, Collis P. Huntington Memorial Hospital of Harvard University, Massachusetts General Hospital, Boston, Massachusetts)

Weanling, young adult, and older rats were partially hepatectomized and given injections intravenously of thymidine-2-C14 at intervals up to 50 hours. They were killed exactly 2 hours after the injection, and the specific activity of the hepatic DNA was determined. The rate of DNA synthesis in weanlings followed a biphasic curve with peaks at approximately 20–22 hours and 33–35 hours after the operation. In adults a delayed, single, broad peak appeared, the maximum response lagging behind the weanlings by 3 hours in young adults (4 months old) and by 8–12 hours in older animals (12–15 months).

It is suggested that the biphasic curve in weanlings may be attributable to the closer synchrony among the responding cells plus the superimposition of a regenerative stimulus upon an already rapidly growing liver, so that repetitive divisions may occur earlier and in a larger fraction of the cellular population than in the older animals. As age advances, the delay in initiating DNA synthesis becomes increasingly longer and synchrony correspondingly poorer. The importance of accurate knowledge of the timing of the maximum response is particularly stressed, since this factor is probably responsible for a good deal of the confusion extant in the literature on hepatic regeneration.

* This is publication No. 1147 of the Cancer Commission of Harvard University.

An earlier report of these findings was presented at meetings of the Federation of American Societies for Experimental Biology (4).

This work was supported by grants E-50A and E-279 from the American Cancer Society Inc. and by grant CA-02146-01 from the National Cancer Institute, National Institutes of Health.

{dagger} Present address: Boston University School of Medicine.

Received 11/ 1/63.


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Copyright © 1964 by the American Association for Cancer Research.