Antisense oligonucleotide complementary to the BamHI-H gene family of Marek's disease virus induced growth arrest of MDCC-MSB1 cells in the S-phase

DNA synthesis was effectively inhibited by antisense oligonucleotide Al com plementary to the BamHI-H gene family in Marek's disease virus (MDV)-derive d lymphoblastoid MDCC-MSB1 cells. When a cell cycle distribution of a total cell population was analyzed by flow cytometry, the proportion of S-phase cells increased in the cell populations by treatment with oligonucleotide A l. Approximately 60-70% of the cells appeared in the S phase for 24 and 36 hr of incubation in the presence of oligonucleotide Al (20-30% in the untre ated control cells). The inhibition of cell cycle progression by treatment with oligonucleotide Al was reversible. When the cells were treated with 5 mu M aphidicolin for 12 hr, a similar pattern of cell cycle distribution wa s observed to that obtained after treatment with oligonucleotide Al. Aphidi colin is an inhibitor of cellular DNA polymerase a. and it halts progressio n of the cell cycle at the G1/S border or early S phase. When the cells wer e treated with aphidicolin for 12 hr and subsequently incubated with oligon ucleotide Al, no significant difference was observed in the cycle phase dis tribution of cells in the presence and absence of oligonucleotide Al. In co ntrast, when the cells were treated with oligonucleotide Al for 12 hr and s ubsequently incubated with aphidicolin, the cell cycle did not progress fro m the G1/S border or early S phase to the next phase.