Effects of partially thiolated polycytidylic acid on the clonogenicity of murine leukemic stem cells.
The effect of partially thiolated polycytidylic acid (MPC) on the colony-forming ability of the progenitor cells (CFUC) of RF/Un leukemic mice was investigated using the plasma clot method in order to study the mode of action of the modified polynucleotide. The results showed that MPC inhibited the CFUC in a dose-dependent and time-dependent manner. Once a maximum level of inhibition of CFUC (approximately 40%) was observed, no further inhibition occurred whether the concentration of MPC was increased or whether the duration of incubation was lengthened. High-specific-activity [3H]thymidine, an S-phase-specific agent, showed a similar inhibition profile on the CFUC as did MPC. When MPC and high-specific-activity [3H]thymidine were incubated together with the bone marrow cells, there was no additive or synergistic inhibitory effect on the CFUC. Thus, it appears that MPC is an S-phase-specific agent. When injected i.v. into the mice, MPC decreased the number of CFUC of both the bone marrow and the spleen significantly.
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002999:Clone Cells / Q000187:drug effects*; D003114:Colony-Forming Units Assay; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D007951:Leukemia, Myeloid / Q000188:drug therapy; D051379:Mice; D011066:Poly C / Q000494:pharmacology*; D011131:Polyribonucleotides / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D013936:Thymidine / Q000494:pharmacology; D014316:Tritium / Q000494:pharmacology
D011131:Polyribonucleotides; D013438:Sulfhydryl Compounds; D014316:Tritium; D011066:Poly C; D013936:Thymidine