Scheduling of Arabinosylcytosine and 6-Thioguanine Therapy

Summary

Mice treated simultaneously with 1-β-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.