Interferon-induced inhibition of a malignant glioma cell line. Possible role of the 2' - 5' oligo (A) system.

The role of the IFN-induced enzyme 2' - 5' oligo (A) synthetase in the regulation of cell growth was analyzed by transfecting its reaction product into cells in the G1 and S phases of the cell cycle. Using the calcium phosphate transfection method, we found that the oligonucleotide was very stable compared to the levels reported to be induced by IFN. Under these circumstances, exponentially growing cells were blocked in the S phase as expected from previous results from studies on IFN treatment. In contrast, cells synchronized by serum starvation and readdition of serum were blocked in the cell cycle phase, where they resided when transfected. Precipitated oligonucleotide had drastic effects with degradation of rRNA and c-myc mRNA, in contrast to IFN-treated cultures where such effects were not detectable. 2' - 5' oligo (A) synthetase activity started to increase 6 hours after restimulation of quiescent cells with IFN and serum. We propose that several molecular targets may exist for the 2' - 5' oligo (A) system, and that the kinetics of expression of the oligonucleotide after addition of IFN determine the type of cell cycle block obtained in different tumor cells in vivo.