Journal Article

Correlation between antioxidant status, tumorigenicity and radiosensitivity in sister rat cell lines

Anne Bravard, Agnès Ageron-Blanc, Sandra Alvarez, Pascal Drané, Yves le Rhun, François Paris, Catherine Luccioni and Evelyne May

in Carcinogenesis

Volume 23, issue 5, pages 705-711
Published in print May 2002 | ISSN: 0143-3334
Published online May 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.5.705
Correlation between antioxidant status, tumorigenicity and radiosensitivity in sister rat cell lines

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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.

Keywords: B[a]P, benzo[a]pyrene; CAT, catalase; CuZn SOD, copper-zinc-containing superoxide dismutase; GPX, glutathione peroxidase; Mn SOD, manganese-containing superoxide dismutase; PBS, phosphate-buffered saline; ROS, reactive oxygen species.

Journal Article.  5522 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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