Open AccessEffects of 5‐fluorouracil on cell cycle arrest and toxicity induced by X‐irradiation in normal mammalian cells
Author(s) -
Nylén U.,
Cekan E.,
Jonasson G.B.,
Lewin F.,
Skog S.
Publication year - 2001
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1046/j.1365-2184.2001.00200.x
Subject(s) - in vivo , cell cycle , toxicity , cytotoxic t cell , fetus , dna damage , cancer research , biology , cell cycle checkpoint , cell growth , fluorouracil , ionizing radiation , cell , in vitro , pharmacology , andrology , irradiation , cancer , medicine , biochemistry , dna , pregnancy , genetics , physics , nuclear physics
. 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 (C 3 H) 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.