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Scheduling of Arabinosylcytosine and 6-Thioguanine Therapy¹

The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, Houston, Texas 77025

Mice treated simultaneously with 1-ß-D-arabinofuranosylcytosine (ara-C) and 6-thioguanine (6-TG) were protected from the lethal effects of 6-TG. No protection was afforded if ara-C was given 16 hr before the 6-TG. DNA synthesis in mouse bone marrow was immediately depressed to 3 to 12% of that of control in various experiments, after treatment with ara-C, 10 to 20 mg/kg; it then rebounded to 148 to 180% of control during the period 8 to 16 hr, and was below control at 24 hr. DNA synthesis in L1210 cells treated in vivo with ara-C was depressed to less than 1% of control and did not begin to recover until almost 16 hr. However, after a second dose of ara-C at 24 hr, DNA synthesis in L1210 cells recovered much more rapidly.

We studied mouse bone marrows and L1210 cells treated with 2'-deoxythioguanosine to determine the persistance of acid-soluble 6-TG nucleotides after a single dose. 6-TG nucleotides declined to low levels in 6 to 8 hr, exhibiting half-times of approximately 3 hr in both tissues.

¹ This work was supported by Grant CA 11788 from the National Cancer Institute, USPHS. A preliminary report of this work has been presented (9).

² Present address: McEachern Laboratory, University of Alberta, Edmonton, Alberta, Canada.

Received 6/ 9/72. Accepted 1/26/73.