Treatment of leukemia L1210 and P388 by arabinosylcytosine-polysaccharide conjugates

Conjugates of 1-beta-D-arabinofuranosylcytosine (araC) with two polysaccharides such as polygalacturonic acid (PGA) and carboxymethylated yeast beta-D-glucan (CMG) were tested for their antileukemic activity in vitro on a L1210 cell line in suspension culture, in soft agar assay and in vivo on L1210, L1210/araC- and P388-leukemia-bearing mice. Both conjugates showed high activity in vitro in soft agar assay, compared with araC. Single administration of PGA-araC or CMG-araC increased the survival time 1.5 x or 1.7 x, respectively, compared with araC in vivo in L1210-leukemia-bearing mice. The conjugates were not active against araC-resistant leukemia line L1210/araC. The marked effect of both PGA-araC and CMG-araC against leukemia L1210 and P388 is probably due to the prolonged release of free araC from conjugates caused by hydrolysis.