Kinetics of Reduction in Viability of Cultured Leukemia L1210 Cells Exposed to Purine Analogs

Abstract

Rates of reduction in viability and degree of cell killing were relatively independent of concentrations when replicating cultured L1210 cells were exposed to increasing concentrations of 6-thioguanine, 6-methylthiopurine ribonucleoside, 9-beta-D-arabinofuranosyl-9H-purine-6-thiol, or 9-ethyl-6-thiopurine. The relative lack of dependence of cell killing rate on cytotoxic concentrations suggest (a) that these agents may be only effective aganinst proliferating cells, and (b) that only limited therapeutic advantage can be gainged by increasing their concentration beyond a minimum effective level. In contrast, the rate and degree of cell killing were dependent upon concentrations when cells were exposed to increasing amounts of 4-aminopyrrolo(2,3-d)pyrimidine-beta-D-ribofuranoside or to 2-fluoroadenosine, indicating that these analogs are not cell-cycle-stage-specific and that nonreplicating cell populations may be sensitive to them.