This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dunn, B. P. Articles by Beer, C. T. Search for Related Content PubMed PubMed Citation Articles by Dunn, B. P. Articles by Beer, C. T.

Effects of the Antineoplastic Alkaloid Acronycine on Nucleoside Uptake and Incorporation into Nucleic Acids by Cultured L5178Y Cells¹

Cancer Research Centre and Department of Biochemistry, University of British Columbia, Vancouver 8, British Columbia, Canada

The antineoplastic alkaloid acronycine inhibits the incorporation of extracellular nucleosides into the RNA and DNA of cultured L5178Y cells. Spectrophotometric and DNA melting temperature studies showed no evidence of an interaction between acronycine and DNA, nor did the drug inhibit the template activity of DNA (when Escherichia coli RNA polymerase was used). Acronycine did not inhibit nucleic acid synthesis in L5178Y cells as measured by the transfer of radioactivity from an intracellular precursor pool prelabeled with radioactive uridine or thymidine into nucleic acids. On the other hand, the alkaloid markedly inhibited the accumulation of extracellular uridine and thymidine as nucleotides in the intracellular precursor pool. Acronycine had no effect on the distribution of radioactivity among the various components (e.g., uridine nucleotides) of the acid-soluble pool in cells incubated with uridine-5-³H, and it had little or no effect on the phosphorylation of uridine by cell extracts. It is suggested that the reduced net uptake of uridine may be due to an alteration in the transport of the nucleoside through the plasma membrane. A similar mechanism may be responsible for the inhibition by acronycine of the uptake of other nucleosides (e.g., thymidine). Acronycine also strongly reduced the net uptake of formate by L5178Y cells but slightly stimulated the accumulation of 2-deoxyglucose. The immediate biochemical and growth-inhibitory effects of acronycine were readily reversible upon removal of the drug.

¹ This investigation was supported by the Medical Research Council of Canada and the National Cancer Institute of Canada.

² Research Fellow, National Cancer Institute of Canada.

³ Research Associate, Medical Research Council of Canada.

Received 11/13/72. Accepted 6/11/73.