Lethal and cytokinetic effects of mitomycin C on cultured human colon cancer cells.

The lethal and cytokinetic effects of mitomycin C (MC) as a function of drug concentration and exposure time were assessed in cultured human colon adenocarcinoma (LoVo) cells using colony formation to determine cell survival and DNA flow cytometry to examine cell cycle perturbation. MC evoked threshold-exponential type 1-hr dose-dependent survival curves in both exponential and stationary growth phases (Dq = 0.4 microgram/ml; Do = 1.0 microgram/ml). In exponentially growing cultures, a given exposure dose of MC induced equitoxic effects regardless of the specific drug concentration and exposure time used with uninterrupted treatment. However, dose fractionation experiments revealed the ability of LoVo cells to partially repair sublethal damage from MC exposure. Cell cycle progression was reversibly delayed or blocked in G2, S, and G1 phases in this order of sensitivity, with a frozen cycle distribution after greater than or equal to 24 hr treatment with 5 microgram of MC per ml. The reversible delay in S-phase traverse without a significant subsequent G2 block may be exploitable for administration of S-phase-specific drugs to maximize cell kill.