Skip to main content
Erschienen in: Journal of Neuro-Oncology 1/2008

01.01.2008 | Lab. Investigation-Human/Animal Tissue

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

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

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2008

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Behin A, Hoang-Xuan K, Carpentier AF, Delattre JY (2003) Primary brain tumours in adults. Lancet 361:323–331PubMedCrossRef Behin A, Hoang-Xuan K, Carpentier AF, Delattre JY (2003) Primary brain tumours in adults. Lancet 361:323–331PubMedCrossRef
2.
Zurück zum Zitat Lesniak MS, Brem H (2004) Targeted therapy for brain tumours. Nat Rev Drug Discov 3:499–508PubMedCrossRef Lesniak MS, Brem H (2004) Targeted therapy for brain tumours. Nat Rev Drug Discov 3:499–508PubMedCrossRef
3.
Zurück zum Zitat Bredel M (2001) Anticancer drug resistance in primary human brain tumors. Brain Res Brain Res Rev 35:161–204PubMedCrossRef Bredel M (2001) Anticancer drug resistance in primary human brain tumors. Brain Res Brain Res Rev 35:161–204PubMedCrossRef
4.
Zurück zum Zitat Bakkenist CJ, Kastan MB (2003) DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421:499–506PubMedCrossRef Bakkenist CJ, Kastan MB (2003) DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421:499–506PubMedCrossRef
5.
Zurück zum Zitat Marot D, Opolon P, Brailly-Tabard S, Elie N, Randrianarison V, Connault E, Foray N, Feunteun J, Perricaudet M (2006) The tumor suppressor activity induced by adenovirus-mediated BRCA1 overexpression is not restricted to breast cancers. Gene Ther 13:235–244PubMedCrossRef Marot D, Opolon P, Brailly-Tabard S, Elie N, Randrianarison V, Connault E, Foray N, Feunteun J, Perricaudet M (2006) The tumor suppressor activity induced by adenovirus-mediated BRCA1 overexpression is not restricted to breast cancers. Gene Ther 13:235–244PubMedCrossRef
6.
Zurück zum Zitat Holland EC (2001) Brain tumor animal models: importance and progress. Curr Opin Oncol 13:143–147PubMedCrossRef Holland EC (2001) Brain tumor animal models: importance and progress. Curr Opin Oncol 13:143–147PubMedCrossRef
7.
Zurück zum Zitat Schlegel J, Piontek G, Kersting M, Schuermann M, Kappler R, Scherthan H, Weghorst C, Buzard G, Mennel H (1999) The p16/Cdkn2a/Ink4a gene is frequently deleted in nitrosourea-induced rat glial tumors. Pathobiology 67:202–206PubMedCrossRef Schlegel J, Piontek G, Kersting M, Schuermann M, Kappler R, Scherthan H, Weghorst C, Buzard G, Mennel H (1999) The p16/Cdkn2a/Ink4a gene is frequently deleted in nitrosourea-induced rat glial tumors. Pathobiology 67:202–206PubMedCrossRef
8.
Zurück zum Zitat Asai A, Miyagi Y, Sugiyama A, Gamanuma M, Hong SH, Takamoto S, Nomura K, Matsutani M, Takakura K, Kuchino Y (1994) Negative effects of wild-type p53 and s-Myc on cellular growth and tumorigenicity of glioma cells. Implication of the tumor suppressor genes for gene therapy. J Neurooncol 19:259–268PubMedCrossRef Asai A, Miyagi Y, Sugiyama A, Gamanuma M, Hong SH, Takamoto S, Nomura K, Matsutani M, Takakura K, Kuchino Y (1994) Negative effects of wild-type p53 and s-Myc on cellular growth and tumorigenicity of glioma cells. Implication of the tumor suppressor genes for gene therapy. J Neurooncol 19:259–268PubMedCrossRef
9.
Zurück zum Zitat Benda P, Lightbody J, Sato G, Levine L, Sweet W (1968) Differentiated rat glial cell strain in tissue culture. Science 161:370–371PubMedCrossRef Benda P, Lightbody J, Sato G, Levine L, Sweet W (1968) Differentiated rat glial cell strain in tissue culture. Science 161:370–371PubMedCrossRef
10.
Zurück zum Zitat Senatus PB, Li Y, Mandigo C, Nichols G, Moise G, Mao Y, Brown MD, Anderson RC, Parsa AT, Brandt-Rauf PW, Bruce JN, Fine RL (2006) Restoration of p53 function for selective Fas-mediated apoptosis in human and rat glioma cells in vitro and in vivo by a p53 COOH-terminal peptide. Mol Cancer Ther 5:20–28PubMedCrossRef Senatus PB, Li Y, Mandigo C, Nichols G, Moise G, Mao Y, Brown MD, Anderson RC, Parsa AT, Brandt-Rauf PW, Bruce JN, Fine RL (2006) Restoration of p53 function for selective Fas-mediated apoptosis in human and rat glioma cells in vitro and in vivo by a p53 COOH-terminal peptide. Mol Cancer Ther 5:20–28PubMedCrossRef
11.
Zurück zum Zitat Ko L, Koestner A, Wechsler W (1980) Morphological characterization of nitrosourea-induced glioma cell lines and clones. Acta Neuropathol (Berl) 51:23–31CrossRef Ko L, Koestner A, Wechsler W (1980) Morphological characterization of nitrosourea-induced glioma cell lines and clones. Acta Neuropathol (Berl) 51:23–31CrossRef
12.
Zurück zum Zitat Zhu Y, Parada LF (2002) The molecular and genetic basis of neurological tumours. Nat Rev Cancer 2:616–626PubMedCrossRef Zhu Y, Parada LF (2002) The molecular and genetic basis of neurological tumours. Nat Rev Cancer 2:616–626PubMedCrossRef
13.
Zurück zum Zitat Corde S, Balosso J, Elleaume H, Renier M, Joubert A, Biston MC, Adam JF, Charvet AM, Brochard T, Le Bas JF, Esteve F, Foray N (2003) Synchrotron photoactivation of cisplatin elicits an extra number of DNA breaks that stimulate RAD51-mediated repair pathways. Cancer Res 63:3221–3227PubMed Corde S, Balosso J, Elleaume H, Renier M, Joubert A, Biston MC, Adam JF, Charvet AM, Brochard T, Le Bas JF, Esteve F, Foray N (2003) Synchrotron photoactivation of cisplatin elicits an extra number of DNA breaks that stimulate RAD51-mediated repair pathways. Cancer Res 63:3221–3227PubMed
14.
Zurück zum Zitat Biston MC, Joubert A, Adam JF, Elleaume H, Bohic S, Charvet AM, Esteve F, Foray N, Balosso J (2004) Cure of Fisher rats bearing radioresistant F98 glioma treated with cis-platinum and irradiated with monochromatic synchrotron X-rays. Cancer Res 64:2317–2323PubMedCrossRef Biston MC, Joubert A, Adam JF, Elleaume H, Bohic S, Charvet AM, Esteve F, Foray N, Balosso J (2004) Cure of Fisher rats bearing radioresistant F98 glioma treated with cis-platinum and irradiated with monochromatic synchrotron X-rays. Cancer Res 64:2317–2323PubMedCrossRef
15.
Zurück zum Zitat Foray N, Priestley A, Alsbeih G, Badie C, Capulas EP, Arlett CF, Malaise EP (1997) Hypersensitivity of ataxia telangiectasia fibroblasts to ionizing radiation is associated with a repair deficiency of DNA double-strand breaks. Int J Radiat Biol 72:271–283PubMedCrossRef Foray N, Priestley A, Alsbeih G, Badie C, Capulas EP, Arlett CF, Malaise EP (1997) Hypersensitivity of ataxia telangiectasia fibroblasts to ionizing radiation is associated with a repair deficiency of DNA double-strand breaks. Int J Radiat Biol 72:271–283PubMedCrossRef
16.
Zurück zum Zitat Foray N, Marot D, Gabriel A, Randrianarison V, Carr AM, Perricaudet M, Ashworth A, Jeggo P (2003) A subset of ATM- and ATR-dependent phosphorylation events requires the BRCA1 protein. Embo J 22:2860–2871PubMedCrossRef Foray N, Marot D, Gabriel A, Randrianarison V, Carr AM, Perricaudet M, Ashworth A, Jeggo P (2003) A subset of ATM- and ATR-dependent phosphorylation events requires the BRCA1 protein. Embo J 22:2860–2871PubMedCrossRef
17.
Zurück zum Zitat Barth RF (1998) Rat brain tumor models in experimental neuro-oncology: the 9L, C6, T9, F98, RG2 (D74), RT-2 and CNS-1 gliomas. J Neurooncol 36:91–102PubMedCrossRef Barth RF (1998) Rat brain tumor models in experimental neuro-oncology: the 9L, C6, T9, F98, RG2 (D74), RT-2 and CNS-1 gliomas. J Neurooncol 36:91–102PubMedCrossRef
18.
Zurück zum Zitat Joubert A, Foray N (2006) Repair of radiation-induced DNA double-strand breaks in human cells: history, progress and controversies (Chapter 10). In: Landseer BR (ed) New Research on DNA Repair. Nova Science, Hauppauge NY Joubert A, Foray N (2006) Repair of radiation-induced DNA double-strand breaks in human cells: history, progress and controversies (Chapter 10). In: Landseer BR (ed) New Research on DNA Repair. Nova Science, Hauppauge NY
19.
Zurück zum Zitat Foray N, Randrianarison V, Marot D, Perricaudet M, Lenoir G, Feunteun J (1999) Gamma-rays-induced death of human cells carrying mutations of BRCA1 or BRCA2. Oncogene 18:7334–7342PubMedCrossRef Foray N, Randrianarison V, Marot D, Perricaudet M, Lenoir G, Feunteun J (1999) Gamma-rays-induced death of human cells carrying mutations of BRCA1 or BRCA2. Oncogene 18:7334–7342PubMedCrossRef
20.
Zurück zum Zitat Lee SA, Dritschilo A, Jung M (2001) Role of ATM in oxidative stress-mediated c-Jun phosphorylation in response to ionizing radiation and CdCl2. J Biol Chem 276:11783–11790PubMedCrossRef Lee SA, Dritschilo A, Jung M (2001) Role of ATM in oxidative stress-mediated c-Jun phosphorylation in response to ionizing radiation and CdCl2. J Biol Chem 276:11783–11790PubMedCrossRef
21.
Zurück zum Zitat Rothkamm K, Lobrich M (2003) Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proc Natl Acad Sci USA 100:5057–5062PubMedCrossRef Rothkamm K, Lobrich M (2003) Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proc Natl Acad Sci USA 100:5057–5062PubMedCrossRef
22.
Zurück zum Zitat Udayakumar D, Bladen CL, Hudson FZ, Dynan WS (2003) Distinct pathways of nonhomologous end joining that are differentially regulated by DNA-dependent protein kinase-mediated phosphorylation. J Biol Chem 278:41631–41635PubMedCrossRef Udayakumar D, Bladen CL, Hudson FZ, Dynan WS (2003) Distinct pathways of nonhomologous end joining that are differentially regulated by DNA-dependent protein kinase-mediated phosphorylation. J Biol Chem 278:41631–41635PubMedCrossRef
23.
Zurück zum Zitat Chavaudra N, Bourhis J, Foray N (2004) Quantified relationship between cellular radiosensitivity, DNA repair defects and chromatin relaxation: a study of 19 human tumour cell lines from different origin. Radiother Oncol 73:373–382PubMedCrossRef Chavaudra N, Bourhis J, Foray N (2004) Quantified relationship between cellular radiosensitivity, DNA repair defects and chromatin relaxation: a study of 19 human tumour cell lines from different origin. Radiother Oncol 73:373–382PubMedCrossRef
24.
Zurück zum Zitat Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J, Ashley T, Livingston DM (1997) Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell 88:265–275PubMedCrossRef Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J, Ashley T, Livingston DM (1997) Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell 88:265–275PubMedCrossRef
25.
Zurück zum Zitat Zan Y, Haag JD, Chen KS, Shepel LA, Wigington D, Wang YR, Hu R, Lopez-Guajardo CC, Brose HL, Porter KI, Leonard RA, Hitt AA, Schommer SL, Elegbede AF, Gould MN (2003) Production of knockout rats using ENU mutagenesis and a yeast-based screening assay. Nat Biotechnol 21:645–651PubMedCrossRef Zan Y, Haag JD, Chen KS, Shepel LA, Wigington D, Wang YR, Hu R, Lopez-Guajardo CC, Brose HL, Porter KI, Leonard RA, Hitt AA, Schommer SL, Elegbede AF, Gould MN (2003) Production of knockout rats using ENU mutagenesis and a yeast-based screening assay. Nat Biotechnol 21:645–651PubMedCrossRef
26.
Zurück zum Zitat Ueki K, Nishikawa R, Nakazato Y, Hirose T, Hirato J, Funada N, Fujimaki T, Hojo S, Kubo O, Ide T, Usui M, Ochiai C, Ito S, Takahashi H, Mukasa A, Asai A, Kirino T (2002) Correlation of histology and molecular genetic analysis of 1p, 19q, 10q, TP53, EGFR, CDK4, and CDKN2A in 91 astrocytic and oligodendroglial tumors. Clin Cancer Res 8:196–201PubMed Ueki K, Nishikawa R, Nakazato Y, Hirose T, Hirato J, Funada N, Fujimaki T, Hojo S, Kubo O, Ide T, Usui M, Ochiai C, Ito S, Takahashi H, Mukasa A, Asai A, Kirino T (2002) Correlation of histology and molecular genetic analysis of 1p, 19q, 10q, TP53, EGFR, CDK4, and CDKN2A in 91 astrocytic and oligodendroglial tumors. Clin Cancer Res 8:196–201PubMed
27.
Zurück zum Zitat Bredel M, Bredel C, Juric D, Harsh GR, Vogel H, Recht LD, Sikic BI (2005) High-resolution genome-wide mapping of genetic alterations in human glial brain tumors. Cancer Res 65:4088–4096PubMedCrossRef Bredel M, Bredel C, Juric D, Harsh GR, Vogel H, Recht LD, Sikic BI (2005) High-resolution genome-wide mapping of genetic alterations in human glial brain tumors. Cancer Res 65:4088–4096PubMedCrossRef
28.
Zurück zum Zitat Ruffner H, Jiang W, Craig AG, Hunter T, Verma IM (1999) BRCA1 is phosphorylated at serine 1497 in vivo at a cyclin-dependent kinase 2 phosphorylation site. Mol Cell Biol 19:4843–4854PubMed Ruffner H, Jiang W, Craig AG, Hunter T, Verma IM (1999) BRCA1 is phosphorylated at serine 1497 in vivo at a cyclin-dependent kinase 2 phosphorylation site. Mol Cell Biol 19:4843–4854PubMed
29.
Zurück zum Zitat Deans AJ, Khanna KK, McNees CJ, Mercurio C, Heierhorst J, McArthur GA (2006) Cyclin-dependent kinase 2 functions in normal DNA repair and is a therapeutic target in BRCA1-deficient cancers. Cancer Res 66:8219–8226PubMedCrossRef Deans AJ, Khanna KK, McNees CJ, Mercurio C, Heierhorst J, McArthur GA (2006) Cyclin-dependent kinase 2 functions in normal DNA repair and is a therapeutic target in BRCA1-deficient cancers. Cancer Res 66:8219–8226PubMedCrossRef
30.
Zurück zum Zitat Chang CH, Horton J, Schoenfeld D, Salazer O, Perez-Tamayo R, Kramer S, Weinstein A, Nelson JS, Tsukada Y (1983) Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas. A joint radiation therapy oncology group and eastern cooperative oncology group study. Cancer 52:997–1007PubMedCrossRef Chang CH, Horton J, Schoenfeld D, Salazer O, Perez-Tamayo R, Kramer S, Weinstein A, Nelson JS, Tsukada Y (1983) Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas. A joint radiation therapy oncology group and eastern cooperative oncology group study. Cancer 52:997–1007PubMedCrossRef
31.
Zurück zum Zitat Wolff JE, Trilling T, Molenkamp G, Egeler RM, Jurgens H (1999) Chemosensitivity of glioma cells in vitro: a meta analysis. J Cancer Res Clin Oncol 125:481–486PubMedCrossRef Wolff JE, Trilling T, Molenkamp G, Egeler RM, Jurgens H (1999) Chemosensitivity of glioma cells in vitro: a meta analysis. J Cancer Res Clin Oncol 125:481–486PubMedCrossRef
32.
Zurück zum Zitat Jenkin RD, Boesel C, Ertel I, Evans A, Hittle R, Ortega J, Sposto R, Wara W, Wilson C, Anderson J et al (1987) Brain-stem tumors in childhood: a prospective randomized trial of irradiation with and without adjuvant CCNU, VCR, and prednisone. A report of the childrens cancer study group. J Neurosurg 66:227–233PubMedCrossRef Jenkin RD, Boesel C, Ertel I, Evans A, Hittle R, Ortega J, Sposto R, Wara W, Wilson C, Anderson J et al (1987) Brain-stem tumors in childhood: a prospective randomized trial of irradiation with and without adjuvant CCNU, VCR, and prednisone. A report of the childrens cancer study group. J Neurosurg 66:227–233PubMedCrossRef
33.
Zurück zum Zitat Sheleg SV, Korotkevich EA, Zhavrid EA, Muravskaya GV, Smeyanovich AF, Shanko YG, Yurkshtovich TL, Bychkovsky PB, Belyaev SA (2002) Local chemotherapy with cisplatin-depot for glioblastoma multiforme. J Neurooncol 60:53–59PubMedCrossRef Sheleg SV, Korotkevich EA, Zhavrid EA, Muravskaya GV, Smeyanovich AF, Shanko YG, Yurkshtovich TL, Bychkovsky PB, Belyaev SA (2002) Local chemotherapy with cisplatin-depot for glioblastoma multiforme. J Neurooncol 60:53–59PubMedCrossRef
34.
Zurück zum Zitat Fehlauer F, Muench M, Rades D, Stalpers LJ, Leenstra S, van der Valk P, Slotman B, Smid EJ, Sminia P (2005) Effects of irradiation and cisplatin on human glioma spheroids: inhibition of cell proliferation and cell migration. J Cancer Res Clin Oncol 131:723–732PubMedCrossRef Fehlauer F, Muench M, Rades D, Stalpers LJ, Leenstra S, van der Valk P, Slotman B, Smid EJ, Sminia P (2005) Effects of irradiation and cisplatin on human glioma spheroids: inhibition of cell proliferation and cell migration. J Cancer Res Clin Oncol 131:723–732PubMedCrossRef
35.
Zurück zum Zitat Taghian A, Ramsay J, Allalunis-Turner J, Budach W, Gioioso D, Pardo F, Okunieff P, Bleehen N, Urtasun R, Suit H (1993) Intrinsic radiation sensitivity may not be the major determinant of the poor clinical outcome of glioblastoma multiforme. Int J Radiat Oncol Biol Phys 25:243–249PubMed Taghian A, Ramsay J, Allalunis-Turner J, Budach W, Gioioso D, Pardo F, Okunieff P, Bleehen N, Urtasun R, Suit H (1993) Intrinsic radiation sensitivity may not be the major determinant of the poor clinical outcome of glioblastoma multiforme. Int J Radiat Oncol Biol Phys 25:243–249PubMed
36.
Zurück zum Zitat Taghian A, Suit H, Pardo F, Gioioso D, Tomkinson K, DuBois W, Gerweck L (1992) In vitro intrinsic radiation sensitivity of glioblastoma multiforme. Int J Radiat Oncol Biol Phys 23:55–62PubMed Taghian A, Suit H, Pardo F, Gioioso D, Tomkinson K, DuBois W, Gerweck L (1992) In vitro intrinsic radiation sensitivity of glioblastoma multiforme. Int J Radiat Oncol Biol Phys 23:55–62PubMed
37.
Zurück zum Zitat Foray N, Marot D, Randrianarison V, Venezia ND, Picard D, Perricaudet M, Favaudon V, Jeggo P (2002) Constitutive association of BRCA1 and c-Abl and its ATM-dependent disruption after irradiation. Mol Cell Biol 22:4020–4032PubMedCrossRef Foray N, Marot D, Randrianarison V, Venezia ND, Picard D, Perricaudet M, Favaudon V, Jeggo P (2002) Constitutive association of BRCA1 and c-Abl and its ATM-dependent disruption after irradiation. Mol Cell Biol 22:4020–4032PubMedCrossRef
38.
Zurück zum Zitat Rosen EM, Fan S, Isaacs C (2005) BRCA1 in hormonal carcinogenesis: basic and clinical research. Endocr Relat Cancer 12:533–548PubMedCrossRef Rosen EM, Fan S, Isaacs C (2005) BRCA1 in hormonal carcinogenesis: basic and clinical research. Endocr Relat Cancer 12:533–548PubMedCrossRef
Metadaten
Titel
Molecular and cellular response of the most extensively used rodent glioma models to radiation and/or cisplatin
verfasst von
Zuzana Bencokova
Laurianne Pauron
Clément Devic
Aurélie Joubert
Jérôme Gastaldo
Catherine Massart
Jacques Balosso
Nicolas Foray
Publikationsdatum
01.01.2008
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 1/2008
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-007-9433-0

Weitere Artikel der Ausgabe 1/2008

Journal of Neuro-Oncology 1/2008 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.