Persistent oxidative stress after ionizing radiation is involved in inherited radiosensitivity.
The SW620IR1 cell line was derived from SW620 human colon cells surviving to ionizing radiations. It shows an increased radiosensitivity and a higher yield of spontaneous chromosomal aberrations. In order to check whether altered reactive oxygen intermediates (ROI) metabolism is involved in this inherited phenotype, we compared the two cell lines for their radiation-induced modifications at the level of ROI production, antioxidant activities, and chromosomal aberrations. Compared to SW620, SW620IR1 cells exhibit a higher and more persistent ROI induction after various doses of ionizing radiations and a higher yield of dicentric chromosomes. They are also characterized by lower basal activities of glutathione peroxidase and manganese-containing superoxide dismutase, and lower ability to induce these antioxidant defenses after irradiation. Resumption of cell growth after irradiation coincides with maximal induction of antioxidant activities and normalization of ROI concentration. However, at that time radiation-induced chromosomal aberrations are not completely eliminated, leading to the proliferation of genetically unstable cells. These results indicate that the inherited sensitivity of SW620IR1 cells is associated with altered antioxidant activities resulting in higher and more prolonged oxidative stress after radiation exposure. They also suggest that the normalization of ROI levels allows these p53 mutant cells to resume proliferation although high levels of DNA damages are still persisting, thereby explaining the chromosomal instability observed as a delayed effect of radiation exposure.
Tulard
Anne
A
Département de Radiobiologie et Radiopathologie, UMR217 CNRS/CEA, Commissariat ă l'Energie Atomique, BP6, F-92265 Fontenay-aux-roses, France. bravard@dsvidf.cea.fr
Hoffschir
Françoise
F
de Boisferon
Florence Hillairet
FH
Luccioni
Catherine
C
Bravard
Anne
A
D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D003106:Colon / Q000166:cytology / Q000528:radiation effects*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D004307:Dose-Response Relationship, Radiation; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D007621:Karyotyping; D018384:Oxidative Stress; D011836:Radiation Tolerance / Q000235:genetics*; D011839:Radiation, Ionizing; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase