Molecular and cellular response of the most extensively used rodent glioma models to radiation and/or cisplatin
Journal title : Journal of neuro-oncology
Volume : 86
Issue : 1
Pagination : 13-21
Publication date : 01/01/2008
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. 2004, 64, 2317-2323). 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 signaling were investigated in the most extensively used rodent
Methods: Cell death pathways, cell cycle arrests, DNA repair and stress signaling 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.