Modification of the response to actinomycin D-induced sublethal damage by simultaneous recovery from potentially lethal damage in mammalian cells.

Exponentially growing cells and cells that were allowed to enter a plateau or nondividing state of growth by depleting the medium of growth-essential nutrients were used in these studies. Nondividing Chinese hamster ovary cells in vitro are less sensitive to actinomycin D (AMD) than are exponentially growing cells. The cells were tested for their ability to recover from AMD-induced potentially lethal damage (PLD) or sublethal damage. The proliferating and the nonproliferating cells do not recover from PLD or sublethal damage, and they experience further reductions in survival when they are maintained under the medium conditions of their respective growth states. However, when dividing cells are placed in conditions suboptimal for growth (incubated in depleted plateau medium after treatment with AMD), they did exhibit increased survival. The PLD recovery was so great under these conditions that it masked the true response of the cells to fractionated doses of AMD. When adjustments were made for the PLD recovery, the resulting data indicated a slight but measurable increase in survival. Since AMD inhibits cell progression in all stages of the cell cycle, this increase in survival observed with fractionated doses of AMD may be due to true recovery from sublethal damage, although the movement of cells into less sensitive stages of the cell cycle between treatments cannot be ruled out.