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Comparative toxicity of mitomycin C and 5-fluorouracil in vitro
S Smith1, P A D'Amore, E B Dreyer
1Laboratory for Surgical Research, Children's Hospital, Boston, Massachusetts.
Abstract:
The adjunctive use of antimetabolites has revolutionized surgical procedures to correct glaucoma in the past decade. Although much is known about the in vitro and in vivo actions of 5-fluorouracil and mitomycin C, their use in the eye has raised new questions about cellular toxicity. For example, filtering blebs after a surgical procedure supplemented with mitomycin C are relatively avascular in comparison with those seen with 5-fluorouracil supplementation. We investigated the effect of 5-fluorouracil and mitomycin C on cultured capillary endothelial cells and fibroblasts. The viability and morphologic characteristics of 3T3 fibroblasts and capillary endothelial cells were studied in light of increasing doses of 5-fluorouracil and mitomycin. Both cell types showed similar sensitivity to mitomycin C. However, fibroblasts were far more sensitive to 5-fluorouracil than were the cultured microvascular endothelial cells. Thus 5-fluorouracil appears to be toxic to fibroblasts while sparing vascular endothelial cells, whereas mitomycin C is cytotoxic for both cell types.
Insights
5-fluorouracil (5-FU) and mitomycin C (MMC) are used in glaucoma surgery. This study found 5-FU is toxic to fibroblasts but spares vascular cells, while MMC harms both cell types.
Area of Science:
- Ophthalmology
- Cell Biology
- Pharmacology
Background:
- Antimetabolites like 5-fluorouracil (5-FU) and mitomycin C (MMC) are crucial in glaucoma surgery.
- Their ocular cellular toxicity warrants further investigation, especially regarding vascularity differences in filtering blebs.
Purpose of the Study:
- To compare the in vitro cellular toxicity of 5-FU and MMC on fibroblasts and capillary endothelial cells.
- To elucidate differential cellular responses to these antimetabolites in ophthalmic surgery.
Main Methods:
- Cultured 3T3 fibroblasts and microvascular endothelial cells were exposed to varying doses of 5-FU and MMC.
- Cell viability and morphology were assessed to determine dose-dependent toxicity.
Main Results:
- Fibroblasts and capillary endothelial cells exhibited similar sensitivity to MMC.
- Fibroblasts were significantly more sensitive to 5-FU than endothelial cells.
- 5-FU demonstrated a selective toxicity profile, sparing vascular endothelial cells.
Conclusions:
- 5-FU exhibits a favorable toxicity profile for ocular surgery by targeting fibroblasts while sparing vascular endothelial cells.
- MMC is cytotoxic to both fibroblasts and vascular endothelial cells, potentially explaining observed avascularity in filtering blebs.
- These findings inform the selection and application of antimetabolites in glaucoma surgical procedures.