Effects of 5-fluorouracil on cell cycle arrest and toxicity induced by X-irradiation in normal mammalian cells

From clinical studies in cancer patients and experimental in vitro studies, there is evidence of an increased cytotoxic effect, and even synergy: when irradiation is combined with 5-fluorouracil (5-FU), The mechanism for this is unclear. Materials and Methods: Mouse fetuses (C3H) have been exposed in vivo to X-irradiation and 5-fluorouracil (5-FU) as single agents or in combination, Cell proliferation, cell cycle progression, fetal survival and incidence of fetal malformations have been studied. Purpose: The aim of this study was to determine possible synergistic cytotoxic effects when 5-FU and ionizing radiation were combined, particularly concerning the regulation of cell cycle progression in proliferating, non malignant mammalian cells in vivo, Results: The combination of low-toxic doses of X-irradiation and 5-FU had a synergistic toxic effect in nonmalignant mouse fetuses in vivo. The cell cycle regulation was perturbed and the radiation-induced G(2)-arrest was eradicated by 5-FU during the initial hours. Conclusions: The time for repair of radiation induced DNA-damage is probably reduced, which may explain the increased toxicity of this combination.