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Molecular and cellular response of the most extensively used rodent glioma models to radiation and/or cisplatin

  • Lab. Investigation-Human/Animal Tissue
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Abstract

Purpose Anti-glioma strategies are generally based on trials involving rodent models whose choice remains based on proliferative capacity and availability. Recently, our group obtained the most protracted survival of rats bearing F98 gliomas by combining synchrotron X-rays and intracerebral cisplatin injection (Biston et al., Cancer Res, 64:2317–2323, 2004). The response to such treatment was suggested to be dependent on BRCA1, a tumour suppressor known to be involved in the response to radiation and cisplatin. In order to verify the impact of BRCA1 functionality upon success of anti-glioma trials, radiobiological features and BRCA1-dependent stress signalling were investigated in the most extensively used rodent glioma models. Methods Cell death pathways, cell cycle arrests, DNA repair and stress signalling were evaluated in response to radiation and cisplatin in C6, 9L and F98 models. Results Rodent glioma models showed a large spectrum of cellular radiation response. Surprisingly, BRCA1 was found to be functionally impaired in C6 and F98 favouring genomic instability, tumour heterogeneity and tolerance of unrepaired DNA damage. Significance Our findings strengthened the importance of the choice of the glioma model on genetic and radiobiological bases, inasmuch as all these rat glioma models are induced by nitrosourea-mediated mutagenesis that may favour specific gene mutations. Particularly, BRCA1 status may condition the response to anti-glioma treatments. Furthermore, since BRCA1 acts as a tumour suppressor in a number of malignancies, our findings raise also the question of the implication of BRCA1 in brain tumours formation.

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Acknowledgements

We would like to thank Drs. E. P Malaise, V. Favaudon and D. Marot for fruitful discussions. The human glioma cell lines were kindly provided by F. Berger and L. Pelletier. Z. B. is a Ph.D. fellowship of Roche-France. A. J. was supported by the Institut de Radioprotection et de Sûreté Nucléaire (IRSN, France). This work was also supported by the Association Pour la Recherche sur l’Ataxie-Telangiectasie (APRAT), Association pour la Recherche contre le Cancer (ARC), the Electricité de France (Comité de Radioprotection), the ETOILE Project (Région Rhône-Alpes and Lyon University).

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Authors and Affiliations

  1. Inserm, U647, ID17, European Synchrotron Radiation Facility, Grenoble, 38043, France

    Zuzana Bencokova, Laurianne Pauron, Clément Devic, Aurélie Joubert, Jérôme Gastaldo, Catherine Massart, Jacques Balosso & Nicolas Foray

  2. Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-aux-Roses, France

    Aurélie Joubert

  3. Département de Cancérologie et d’Hématologie, CHU Michallon, Grenoble, France

    Jacques Balosso

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  1. Zuzana Bencokova
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Correspondence to Nicolas Foray.

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Bencokova, Z., Pauron, L., Devic, C. et al. Molecular and cellular response of the most extensively used rodent glioma models to radiation and/or cisplatin. J Neurooncol 86, 13–21 (2008). https://doi.org/10.1007/s11060-007-9433-0

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  • DOI: https://doi.org/10.1007/s11060-007-9433-0

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