Selective cytotoxicity of 5-hydroxyuridine for human colon adenocarcinoma cells

The cytotoxicity of 5-hydroxyuridine (OHUrd), 5-FU, and 5-fluorodeoxyuridine was determined by colony assays for three human colon adenocarcinoma cell lines and for a cell line derived from normal fetal intestinal cells. All three tumor cell lines were more sensitive to OHUrd than were the FeInt cells, whereas 5-FU was more toxic to the latter. 5-Fluorodeoxyuridine was substantially more cytotoxic to only one of the tumor cell lines compared to the normal cells. In HT-29 tumor cells, OHUrd cytotoxicity could be prevented by coincubation with uridine or cytidine but not by pyrimidine deoxyribonucleosides or by purine nucleosides. Compared to OHUrd, 5-hydroxyuracil was much less cytotoxic for HT-29 cells. The increased cytotoxicity of OHUrd for these tumor cells compared to fetal intestinal cells may implicate biochemical differences that might be exploitable for improved chemotherapy. Direct comparison of drug sensitivity of colon tumor cells compared to normal counterpart cells may provide a method of screening agents selective for these tumor cells.