Temperature sensitivity of poly(ADP-ribose) synthetase in intact cells.

The response of cells to various poly(ADP-ribose) synthetase inhibitors may vary with the cell type and inhibitor type. We have observed that most cells show an inhibition of growth, at least transiently, when exposed to synthetase inhibitors. For one cell type, there is, in contrast, a stimulation of proliferation. These results suggest that the synthetase plays different roles in different cell types or, the inhibitors also affect other cell processes that are variably represented in the different cell types. Because of these difficulties we have sought alternative methods of modulating poly(ADP-ribose) synthetase activity in intact cells. A method of inactivating the synthetase by heat shock is described and the consequences of this inactivation for the repair of single strand breaks in DNA is presented. Additionally, a method for elevating the synthetase in intact cells is given.