title: Correlation between antioxidant status, tumorigenicity and radiosensitivity in sister rat cell lines.
abstract: Tumorigenicity and radiosensitivity of related cell lines expressing distinct p53 mutants were analyzed in parallel with key components of the antioxidant metabolic pathway. Six sublines deriving from the same parental cell population and expressing either the mutant p53K130R or p53V270F were investigated. Both mutations abrogate the transcriptional activity of p53 as well as its ability to induce apoptosis. The cells expressing p53K130R showed a higher tumorigenicity and a higher radiosensitivity than those expressing p53V270F. An increase in tumorigenicity was associated with a decrease in manganese-containing superoxide dismutase activity, and with further decreases in the glutathione content and glutathione peroxidase (GPX) activity. A positive correlation was found between GPX activity, glutathione content and cell survival following ionizing irradiation. The fact that sister cell lines exhibit different tumorigenicity and radiosensitivity while expressing a mutant p53 further supports the notion that knowledge of p53 status is not sufficient to predict tumor outcome, especially the response to irradiation. A better understanding of antioxidant defenses might be more informative.
authors.affiliation: Commissariat à l'Energie Atomique (CEA), DSV/DRR/Laboratoire de Radiobiologie Cellulaire and Commissariat à l'Energie Atomique (CEA), UMR217 CEA-CNRS, Fontenay-aux-Roses Cedex, France. bravard@dsvidf.cea.fr
authors.forename: Anne
authors.initials: A
authors.lastname: Bravard
authors.forename: Agnès
authors.initials: A
authors.lastname: Ageron-Blanc
authors.forename: Sandra
authors.initials: S
authors.lastname: Alvarez
authors.forename: Pascal
authors.initials: P
authors.lastname: Drané
authors.forename: Yves
authors.initials: Y
authors.lastname: Le Rhun
authors.forename: François
authors.initials: F
authors.lastname: Paris
authors.forename: Catherine
authors.initials: C
authors.lastname: Luccioni
authors.forename: Evelyne
authors.initials: E
authors.lastname: May
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D011836:Radiation Tolerance; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione