Inhibited methionine incorporation in human squamous carcinomas of the oral cavity as a measure for response to 5-fluorouracil

Abstract

Human epithelial cells and fibroblasts from malignant tumors and healthy tissues of the oral cavity were exposed in vitro to increasing concentrations of 5-fluorouracil. In order to determine whether the two cell types showed a difference in uptake, accumulation was measured over time using tritiated fluorouracil. Maximal drug uptake occurred in highly proliferative epithelial cells from cancerous tissue at 3 h, whereas fibroblasts from the same tissue and other cell types from healthy tissue exhibited a steadily increasing uptake over a long period of time. By use of [3H]methionine, a direct correlation could be demonstrated between the amount of incorporated drug and the fall in the rate of de novo protein synthesis. Furthermore, suppression of protein synthesis was closely related to the inhibition of cell division. These results indicate that the level of de novo protein synthesis can be a direct measure of the anticancer effect of fluorouracil.