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-β-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 against 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-β-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.

Interaction of 3,4,5,6-tetrahydrouridine with human liver cytidine deaminase

“…The action of cytidine deaminase on the antineoplastic agent cytosine arabinoside (Camiener and Smith, 1965) to yield an apparently inert product (Chu and Fischer, 1962;Wilkoff et al, 1972) presumably limits this agent's effectiveness in the treatment of human leukemias (Body et al, 1969). The observation that THU is a potent inhibitor of the enzyme from human liver and from HeLa cells, as well as the enzyme from human granulocytes as previously reported by Chabner et al (1974), suggests the chemotherapeutic use of THU with cytosine arabinoside.…”