Abstract
Abstract: :
Purpose: To determine the minimum inhibitory concentration of human lens epithelial cell growth using 5–fluorouracil (5–FU). Methods: A clone of human lens epithelial cells was exposed to five different log unit concentrations of the antimetabolite 5–FU. Five different sets of cells had decreasing log unit doses of 5–FU from 50 mg/ml to 5 x 10–3 mg/ml added for 5 minutes and rinsed. The cells were then incubated and counted at days 5 and 10 following the 5–FU exposure. The automated count for each dose was then compared to the control group. Cell viability was also evaluated. Two sets of cells were exposed to the five concentrations of 5–FU and stained with trypan blue. A manual count of viable cells on each slide was determined in five high powered fields and compared to controls. Results: At day 5, the control group had an average automated cell count of 2.5 x 106. The cells exposed to 5–FU were significantly inhibited compared to controls at all concentrations studied. The cell counts ranged from 1.53 x 106 at the lowest concentration 5 x 10–3 mg/ml (p=0.04), to 0.7 x 106 at the highest concentration 50 mg/ml (p=6 x 10–8). At day 10, the control group had an average automated count of 3.79 x 106. The 5–FU groups with concentrations of 0.5, 5.0, and 50 mg/ml had reduced cell numbers of 1.63, 0.72, and 0.38 million, respectively. These counts were statistically significant when compared to day 10 controls. At dilutions of 0.05 mg/ml and below, the cell growth was similar to the control group. Viability studies with trypan blue had reduced cell numbers at concentrations of 0.5 mg/ml and above at both day 5 and 10. Conclusions: 5–Fluorouracil (5–FU) is a potent inhibitor of human lens epithelial cell growth at concentrations of 0.5 mg/ml or greater. Intraocular 5–FU could be used to prevent posterior capsular opacification. Further studies on the intraocular toxicity of 5–Fluorouracil used for short periods at these doses are needed.
Keywords: drug toxicity/drug effects • posterior capsular opacification (PCO) • cell death/apoptosis