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In vitro effects of mitomycin-C on human keratocytes
H M Sadeghi1, B Seitz, S Hayashi
1Doheny Eye Institute, Los Angeles 90033, USA.
Background:
The purpose of the present study is to quantify the in vitro antiproliferative and cytotoxic effects of mitomycin-C on human keratocytes for their potential to modulate corneal stromal wound healing.
Methods:
Cultured human keratocytes were exposed to various concentrations of mitomycin-C for periods of 5 minutes and 1 hour. Keratocyte proliferation and viability were assessed by phase-contrast microscopy, 3H-thymidine uptake, and electronic cell counting.
Results:
Cytotoxic changes and inhibition of keratocyte proliferation exhibited after exposure to mitomycin-C were both dose- and time-dependent. The lowest concentrations to significantly (> 50%) inhibit keratocyte proliferation after 5-minute exposures were 0.05 mg/ml (P < .005) and after 1-hour exposures were 0.005 mg/ml (P < .001). At 5 minutes, ID50 was 0.038 mg/ml and LD50 was much higher than the greatest concentration tested (0.5 mg/ml). Mitomycin-C's median inhibitory dose (ID50) and median lethal dose (LD50) after 1 hour of exposure differed by a magnitude of 50 (0.0048 vs. 0.28 mg/ml).
Conclusions:
Mitomycin-C has antiproliferative effects at concentrations below those cytotoxic to human keratocytes. If used after photorefractive keratectomy, the drug should be administered at antiproliferative rather than cytotoxic concentrations.