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.
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.
Authors: Matthew J Simpson; Katrina K Treloar; Benjamin J Binder; Parvathi Haridas; Kerry J Manton; David I Leavesley; D L Sean McElwain; Ruth E Baker Journal: J R Soc Interface Date: 2013-02-20 Impact factor: 4.118
Authors: Sean T Vittadello; Scott W McCue; Gency Gunasingh; Nikolas K Haass; Matthew J Simpson Journal: Biophys J Date: 2018-03-13 Impact factor: 4.033
Authors: Danielle M Robertson; Jerry P Kalangara; Rebeccah B Baucom; W Matthew Petroll; H Dwight Cavanagh Journal: Curr Eye Res Date: 2011-08 Impact factor: 2.424
Authors: Ahmad Shabsigh; Nir Kleinmann; Angela B Smith; Douglas Scherr; Elyse Seltzer; Mark Schoenberg; Seth P Lerner Journal: Cancer Chemother Pharmacol Date: 2021-03-07 Impact factor: 3.333
Authors: Katrina K Treloar; Matthew J Simpson; Parvathi Haridas; Kerry J Manton; David I Leavesley; D L Sean McElwain; Ruth E Baker Journal: BMC Syst Biol Date: 2013-12-12
Authors: Katrina K Treloar; Matthew J Simpson; Benjamin J Binder; D L Sean McElwain; Ruth E Baker Journal: Sci Rep Date: 2014-07-16 Impact factor: 4.379