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.


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.


OBJECTIVE
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 G2-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.
Nylén
U
U
Department of Oncology and Pathology, Sections for Medical Radiobiology and General Oncology, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden. urban.nylen@onkpat.ki.se
Cekan
E
E
Jonasson
G B
GB
Lewin
F
F
Skog
S
S
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004622:Embryo, Mammalian / Q000166:cytology* / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D005260:Female; D005313:Fetal Death; D005472:Fluorouracil / Q000633:toxicity*; D018811:Maternal Exposure; D051379:Mice; D008809:Mice, Inbred C3H; D014916:Whole-Body Irradiation; D014965:X-Rays / Q000009:adverse effects*
D005472:Fluorouracil