A proliferation-related constraint on endogenous and interferon-induced 2-5A synthetase activity in normal and...

2-5A Synthetase is one of the most extensively characterized enzymes induced by interferon (IFN) and is the central enzyme in a pathway that may be involved in the control of cellular proliferation. We examined the activity of this enzyme in normal diploid Syrian hamster cells (FC13) and their neoplastically transformed derivatives (BP6T); the former cell strain possesses regulated proliferative control, while the latter cell line has escaped from this control. A significant threefold increase in 2-5A synthetase activity was observed in density-arrested versus proliferating FC13 cells, whereas endogenous enzyme activity was uniformly low in BP6T cultures. The increase in enzyme activity in FC13 cultures was not accompanied by the production of IFN at a detectable level, but was parallelled by an increase in the intracellular level of 2',5'-oligoadenylate. IFN treatment resulted in a differential induction of enzyme activity depending on the proliferative state of FC13 cells. After IFN treatment, BP6T cells and subconfluent FC13 cells responded similarly with a fivefold increase in enzyme activity, whereas confluent FC13 cells displayed only a 1.4-fold increase. 2-5A Synthetase enzyme activity reflected steady-state mRNA levels in BP6T and subconfluent FC13 cells. In contrast, a noncoordinate regulation of 2-5A synthetase mRNA expression and enzyme activity was detected in confluent FC13 cells, suggesting that posttranscriptional mechanisms may be involved. The different patterns of endogenous and IFN-induced 2-5A synthetase enzyme activity in FC13 and BP6T cells found in this comparative study may represent an alteration fundamental to the loss of proliferative control in transformed cells.