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Effect of Neocarzinostatin on DNA Synthesis in L1210 Cells¹

The First Division of Internal Medicine, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606 Japan

The mechanism of action of neocarzinostatin has been investigated. The synthesis of DNA in L1210 cells in vivo was selectively inhibited by the drug. DNA synthesis in vitro catalyzed by crude DNA-dependent DNA polymerase of L1210 cells was sensitive to the drug in a concentration-dependent manner. This inhibition was reversed by increasing the concentration of DNA. Evidence for a DNA-drug interaction was obtained from the results of the preincubation of DNA with the component in the DNA polymerase reaction and from thermal denaturation studies. The degradation of cellular DNA in vivo by the drug was also suggested by the sedimentation profile in the alkaline sucrose gradient centrifugation.

¹ Supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education and the Ministry of Health and Welfare of Japan.

Received 6/10/74. Accepted 7/ 3/74.

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