Sadeghi H M, Seitz B, Hayashi S, LaBree L, McDonnell P J
Doheny Eye Institute, Los Angeles 90033, USA.
J Refract Surg. 1998 Sep-Oct;14(5):534-40. doi: 10.3928/1081-597X-19980901-11.
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.
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.
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).
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.
本研究的目的是量化丝裂霉素C对人角膜细胞的体外抗增殖和细胞毒性作用，以评估其调节角膜基质伤口愈合的潜力。
将培养的人角膜细胞暴露于不同浓度的丝裂霉素C中5分钟和1小时。通过相差显微镜、³H-胸腺嘧啶核苷摄取和电子细胞计数评估角膜细胞的增殖和活力。
暴露于丝裂霉素C后出现的细胞毒性变化和角膜细胞增殖抑制均呈剂量和时间依赖性。5分钟暴露后显著（>50%）抑制角膜细胞增殖的最低浓度为0.05 mg/ml（P<.005），1小时暴露后为0.005 mg/ml（P<.001）。5分钟时，半数抑制剂量（ID50）为0.038 mg/ml，半数致死剂量（LD50）远高于测试的最大浓度（0.5 mg/ml）。暴露1小时后，丝裂霉素C的半数抑制剂量（ID50）和半数致死剂量（LD50）相差50倍（0.0048对0.28 mg/ml）。
丝裂霉素C在低于对人角膜细胞具有细胞毒性的浓度下具有抗增殖作用。如果在准分子激光原位角膜磨镶术后使用，该药物应以抗增殖而非细胞毒性浓度给药。
