The effect of ara-C on survival and proliferation of HeLa cells. A time-lapse cinematographic and light microscopic study.

The cytocidal and cytostatic effect of ara-C on HeLa cells was studied by cell counting and time-lapse cinematography. The effect of ara-C clearly depended on the dose and duration of the treatment. Continuous exposure to ara-C above a threshold dose of about 0.5 microgram/ml killed almost all cells within 2 days. Short-term incubation (3 h) with high doses (200 and 400 micrograms/ml) led to death of the cultures within 5 days. On the other hand short-term exposure to low ara-C doses (4 and 20 micrograms/ml) exhibited mainly a cytostatic with no substantial cytocidal effect. Time-lapse studies on the fate of HeLa cells have shown directly that cells lethally damaged by ara-C die out of interphase. The present results confirm the S phase specific effect of ara-C: lethally damaged cells had shorter survival times, if they were in S phase during short-term drug exposure or at the time of drug addition in the case of continuous incubation. Most important with respect to the therapeutic use of ara-C was the effect on the cycle time. Not only the cycle that included the short-term treatment but also the next cycle of those cells that survived the treatment was prolonged (from 19 h to 29 h). Furthermore, these prolonged cycle times varied considerably compared to those of untreated controls.