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Deamination of Arabinosyladenine by Adenosine Deaminase and Inhibition by Arabinosyl-6-mercaptopurine¹

Department of Biophysical Sciences, University of Houston, Houston, Texas 77004

6-Mercapto-9-(ß-D-arabinofuranosyl)purine (ara-6-MP) was found to be a competitive inhibitor of L1210 adenosine deaminase when ß-D-arabinosyladenine (ara-A) was used as substrate (pseudoproduct inhibition). The phosphorylation of adenosine, ara-A, and ß-D-ribosyl-6-methylthiopurine did not appear to be affected by ara-6-MP. Studies on the kinetic parameters of adenosine deaminase from two L1210 lines, ara-6-MP-sensitive L1210 and ara-6-MP-resistant L1210 (L1210/ara-6-MP), indicated that the L1210/ara-6-MP subline had mutated. Mice bearing L1210 cells survived longer when treated with ara-A plus ara-6-MP than when treated with either agent alone. No such advantage of the combination drug treatment was seen with mice bearing the line resistant to ara-6-MP (L1210/ara-6-MP).

¹ Supported by Grant CA12327 from the National Cancer Institute of the NIH.

Received 1/31/72. Accepted 4/27/72.