Azapyrimidine analogues: inhibition of viral DNA synthesis and protein synthesis in SV40 infected BSC-1 cells.
The replication of simian virus 40 DNA and protein synthesis in BSC-1 cells was analyzed in vitro after treatment with 5,6-dihydro-5-azacytidine (DH-5-AzaCR) or 5-azacytidine (5-AzaCR). Results demonstrated that after a 3-h treatment period with 100 micrograms/ml, DH-5-AzaCR exhibited a 77% inhibition of viral DNA synthesis, whereas 5-AzaCR resulted in a 50% inhibition. Stimulation of DNA synthesis occurred when infected cultures were treated with low doses (0.1 to 0.5 microgram/ml) of 5-AzaCR for 3 h and after 1 and 2 h of treatment with 100 micrograms/ml of 5-AzaCR; however, stimulation did not occur with DH-5-AzaCR. DNA synthesized in the presence of either drug demonstrated altered conformations when analyzed on agarose gels; however this alteration was negligible after DH-5-AzaCR treatment, but more pronounced in the presence of 5-AzaCR. Restriction enzyme analysis suggests that DH-5-AzaCR may not be a hypomethylating agent as is 5-AzaCR. Inhibition of total protein synthesis (cellular and viral) was essentially complete 6 h after treatment with DH-5-AzaCR, whereas 5-AzaCR completely inhibited protein synthesis after 3 h. These data indicate that 5-AzaCR does not exhibit a direct dose relationship to the inhibition of DNA synthesis whereas DH-5-AzaCR may show some dose relationship, and that DH-5-AzaCR is a more potent inhibitor of DNA synthesis as compared to 5-AzaCR.
Johnson-Thompson
M
M
Department of Biology, University of the District of Columbia, Washington 20005.
Albury
D
D
D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D004279:DNA, Viral / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D008745:Methylation; D014176:Protein Biosynthesis; D013539:Simian virus 40 / Q000187:drug effects / Q000254:growth & development*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*
D004279:DNA, Viral; C013938:5,6-dihydro-5-azacytidine; D001374:Azacitidine