Molecular Pharmacology, Vol 4, 358-366, Copyright © 1968 by the American Society for Pharmacology and Experimental Therapeutics

The Effect of Adenosine N¹-Oxide on the Incorporation of Radioactive Precursors into the Nucleic Acids

¹ Biochemical Department B, Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark

Adenosine N¹-oxide is phosphorylated by Ehrlich ascites tumor cells to AMP N¹-oxide and ATP N¹-oxide. In Ehrlich cells incubated with adenosine N¹-oxide the incorporation of thymidine-³H and ³²P into DNA is inhibited. The results indicate that AMP N¹-oxide or ATP N¹-oxide is responsible for the inhibition. The incorporation of ³²P and uridine-³H into RNA is not inhibited by the analog. The inhibitory effect of adenosine N¹-oxide[unknown] on the incorporation of thymidine-³H into DNA can be abolished by the addition of 2'-deoxycytidine, cytidine, and to some extent uridine, but cytosine and 2'-deoxyguanosine have no effect on the inhibition. Adenosine N¹-oxide inhibits the incorporation of adenine-³H and orotic acid-³H into both DNA and RNA. In the case of adenine-³H this is shown to be due partly to a decreased uptake of the tracer into the ATP pool.

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ACKNOWLEDGMENTS The authors thank Professor H. Klenow for valuable discussions, and Mrs. Inge Kirkeby Hansen for excellent technical assistance.