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Mechanism of Inhibition of DNA Synthesis of Sarcoma 180 Cells by Liver Extract¹

Institute for Muscle Research at the Marine Biological Laboratory, Woods Hole, Massachusetts 02543

The inhibitory activity of liver extracts on thymidine incorporation into DNA was markedly enhanced by manganese and zinc. Manganese-activated liver extract (Mn-liver extract) also inhibited incorporation of deoxycytidine and adenine into DNA. The Mn-liver extract had no effect on incorporation of thymidine-5'-triphosphate into DNA but blocked the phosphorylation of deoxythymidine. The phosphorylation of deoxycytidine into deoxycytidine-5'-triphosphate was not inhibited by Mn-liver extract. The results indicate that the inhibition of synthesis of thymidine-5'-triphosphate is the primary locus in the blocking of DNA synthesis and that the inhibition of incorporation of deoxycytidine into DNA is secondary to the lack of thymidine-5'-triphosphate.

¹ This research was supported by Grant No. GM-10383 to Albert Szent-Györgyi.

² Present address: Department of Biophysics and Biochemistry, Faculty of Sciences, University of Tokyo, Hongo, Tokyo, Japan.

Received 9/24/68. Accepted 5/16/69.