Effect of mitomycin C on prostacyclin synthesis by human endothelial cells

The effect of mitomycin C (MMC) on the biosynthesis of prostacyclin was tested in culture of human umbilical cord vein endothelial cells. A 30% inhibition of the thrombin-stimulated prostacyclin synthesis by MMC was observed at concentrations of the same order as those found in MMC-treated patients (3 micrograms/ml as compared with the peak plasma concentration varying between 0.4 and 3.2 micrograms/ml (J. Den Hartigh et al., Cancer Res 40:5017-5021, 1983)). This inhibition was found for incubation times ranging from 15 to 30 min during which the cell viability was unaltered. Under these conditions it was found that the release of von Willebrand factor by the endothelial cell was unaffected. Since MMC toxicity in man is expressed by a chronic haemolytic and uraemic syndrome, the inhibitory capacity of MMC on prostacyclin synthesis favours the hypothesis that a deficiency in prostacyclin synthesis leads to the development of this syndrome in man.