Influence of drugs on macromolecular synthesis during cell synchronization.

A cell culture system has been used to examine the effect of various pharmacologic agents on DNA synthesis with the hope of utilizing this system for the evaluation of drugs at the cellular level. Glucocorticoids have been shown to have a differential effect on growth dependent on the cell type studied. For this reason steroidal anti-inflammatory agents were chosen to study in our culture system. Aspirin, a non-steroidal anti-inflammatory agent, was also studied for a comparison with glucocorticoids. The CNS stimulants, caffeine and amphetamines, were studied for their effects on non-target cells in culture and compared with the response of target cells. Doxorubicin, an anti-neoplastic agent, has been shown to depress growth in a variety of cells. This drug was also studied in our culture system. We have found that steroidal anti-inflammatory drugs induced a dose-dependent stimulation of DNA synthesis in normal human fibroblasts that was also age-dependent, while decreasing DNA synthesis in SV40 virus transformed cells. Aspirin (25 micrograms/ml) exhibited a similar response. Human fibroblasts were found to be responsive to the CNS stimulants, exhibiting a dose-dependent decrease in DNA synthesis when exposed to caffeine. Amphetamine (200 microM) depressed DNA synthesis in normal fibroblasts and increased it in SV40 virus transformed cells. All cells studied exhibited a depression of DNA synthesis when treated with doxorubicin (0.1 microgram/ml).