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Lethal and Cytokinetic Effects of Mitomycin C on Cultured Human Colon Cancer Cells¹

Departments of Developmental Therapeutics [B. B.] and Laboratory Medicine [B. D.], The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77030

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 (D_q = 0.4 µg/ml; D_o = 1.0 µg/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 24 hr treatment with 5 µg of MC per ml. The reversible delay in S-phase traverse without a significant subsequent G₂ block may be exploitable for administration of Sphase-specific drugs to maximize cell kill.

¹ Supported in part by Grants CA-14528 and CA-23272 from the National Cancer Institute, NIH, Bethesda, Md. 20205.

² Junior Faculty Fellow of the American Cancer Society. To whom requests for reprints should be addressed.

Received 7/30/79. Accepted 3/12/80.