EFFECT OF 7-CON-O-METHYLNOGAROL ON DNA-SYNTHESIS, SURVIVAL, AND CELL-CYCLE PROGRESSION OF CHINESE-HAMSTER OVARY CELLS

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  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (12) , 4981-4987
Abstract
The effect of 7-con-O-methylnogarol (7-OMEN) [an antitumor agent] on the survival of exponentially growing and plateau-phase Chinese hamster ovary [CHO] cells was determined in a cloning assay. After 2 h of exposure, the 50% lethal dose for exponential and plateau-phase cells was 0.3 and 1.5 .mu.g/ml, respectively. Drug doses for cell progression studies were based upon drug lethality; therefore, higher doses were used for plateau than for exponential populations. The effect of 7-OMEN on cell progression was studied by DNA flow cytometry under the following conditions; during 24 h of continuous exposure of exponetially growing cells; during recovery of exponential cells after 2 or 7 h of drug exposure and during recovery of plateau-phase cells after 2 h of exposure. Exponential cells exposed continuously for 24 h progressed normally from M to G1 phase and from G1 to S phase, progression through S phase was slowed and cells were ultimately blocked in G2 + M. Inhibition of S-phase progression was dose dependent, 0.2 .mu.g/ml having only slight effect and 1.0 .mu.g/ml accumulating a large fraction in S phase. Inhibition of S-phase progression correlated with DNA synthesis inhibition. Similar inhibitory effects were observed after pulsed (2- or 7-h) exposure of exponential cells. 7-OMEN also blocked plateau-phase cells in G2 + M after 2 h of exposure, but higher doses (3.0 .mu.g/ml) were required. Simultaneous exposure of exponential cells to colcemid (which blocks cells in metaphase) and 1.0 .mu.g 7-OMEN per ml completely inhibited the expected increase in mitotic index, indicating that the G2 + M block observed by DNA flow cytometry was a block in G2 or prophase.