Radiopotentiation of human brain tumor cells by sodium phenylacetate

Phenylacetate (PA) inhibits the growth of tumor cells in vitro and in vivo and shows promise as a relatively nontoxic agent for cancer treatment. A re cent report shows that prolonged exposure of cells to low concentrations of PA can enhance the radiation response of brain tumor cells in vitro, openi ng up the possibility of using this drug to improve the radiation therapy o f brain tumor patients. We investigated the cytotoxicity produced by sodium phenylacetate (NaPA) alone and in combination with Xrays in SF-767 human g lioblastoma cells and in two medulloblastoma cell lines, Masden and Daoy. E xposure of all three cell lines to relatively low concentrations of NaPA fo r up to 5 days did not enhance the subsequent cell killing produced by X-ir radiation. However, enhanced cell killing was achieved by exposing either o xic or hypoxic cells to relatively high drug concentrations (>50-70 mM) for 1 h immediately before X-irradiation. Because central nervous system toxic ity can occur in humans at serum concentrations of similar to 6 mM PA, tran slation of these results into clinical trials will likely require local dru g-delivery strategies to achieve drug concentrations that can enhance the r adiation response. The safety of such an approach with this drug has not be en demonstrated. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved .