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Searches for Exploitable Biochemical Differences between Normal and Cancer Cells

V. Cellular Conservation of Purines^*

( Kettering-Meyer Laboratory, Southern Research Institute, Birmingham, Ala.)

The feasibility of the hypothesis that rate of cell division might be controlled by a balance between anabolic events leading to nucleic acids and catabolic events which degrade potential nucleic acid precursors has been studied in both in vivo and in vitro systems.

Rapidly growing Sarcoma 180 appears to conserve essentially all its cellular purine derivatives (DNA, RNA, and acid-soluble nucleotides) synthesized de novo or labeled by adenine-8-C¹⁴. Similar results were obtained with human cancer cells growing in tissue culture. In both Sarcoma 180 and in tissue culture, the soluble fraction maintained a level of radioactive purine derivatives manyfold greater than that to be expected after the large amount of nucleic acid synthesis required for the increases in cell number.

This persistence of soluble radioactivity suggests a return of labeled molecules from polynucleotides to the soluble fraction. Further evidence of equilibrium or exchange between polynucleotides and soluble pools was obtained in experiments with Ehrlich ascites cells labeled with adenine-8-C¹⁴. During rapid growth of these cells, the relative labeling of adenine and guanine in the RNA, but not in DNA, changed significantly, a phenomenon possibly indicating breakdown of RNA and reutilization of the breakdown products.

^* This work was supported by grants from the C. F. Kettering Foundation; the Alfred P. Sloan Foundation; the Biology and Medicine Division, U.S. Atomic Energy Commission; and by the Cancer Chemotherapy National Service Center under National Institutes of Health Contract No. SA-43-ph-1741. Presented in part before the American Association for Cancer Research, Inc., April, 1959.

Affiliated with Sloan-Kettering Institute for Cancer Research, New York.

Received 6/30/59.