Effects of 2',3'-dideoxythymidine triphosphate on replicative DNA synthesis and unscheduled DNA synthesis in permeable mouse sarcoma cells.
2',3'-Dideoxythymidine triphosphate differentially inhibited replicative DNA synthesis in permeable mouse ascites sarcoma cells and unscheduled DNA synthesis in bleomycin-treated permeable cells or in isolated rat liver nuclei. The mode of inhibition of 2',3'-dideoxythymidine triphosphate was competitive with respect to deoxythymidine triphosphate. 2',3'-Dideoxythymidine triphosphate inhibited replicative DNA synthesis with a Ki of 8 microM, whereas unscheduled DNA synthesis was more sensitive, the Ki being 0.5 microM. Referring to the differential sensitivity of DNA polymerases alpha and beta to 2',3'-dideoxythymidine triphosphate and to other related information reported previously, the present results suggested that DNA polymerase alpha is playing a major role in replicative DNA synthesis, and DNA polymerase beta in unscheduled DNA synthesis.
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D054306:Dideoxynucleotides; D051379:Mice; D012513:Sarcoma, Experimental / Q000378:metabolism*; D013942:Thymine Nucleotides / Q000494:pharmacology*
D004273:DNA, Neoplasm; D054306:Dideoxynucleotides; D013942:Thymine Nucleotides; D001761:Bleomycin; D004259:DNA-Directed DNA Polymerase; C017216:2',3'-dideoxythymidine triphosphate