title: Cellular and molecular portrait of eleven human glioblastoma cell lines under photon and carbon ion irradiation.
abstract: This study aimed to examine the cellular and molecular long-term responses of glioblastomas to radiotherapy and hadrontherapy in order to better understand the biological effects of carbon beams in cancer treatment. Eleven human glioblastoma cell lines, displaying gradual radiosensitivity, were irradiated with photons or carbon ions. Independently of p53 or O(6)-methylguanine-DNA methyltransferase(1) status, all cell lines responded to irradiation by a G2/M phase arrest followed by the appearance of mitotic catastrophe, which was concluded by a ceramide-dependent-apoptotic cell death. Statistical analysis demonstrated that: (i) the SF2(2) and the D10(3) values for photon are correlated with that obtained in response to carbon ions; (ii) regardless of the p53, MGMT status, and radiosensitivity, the release of ceramide is associated with the induction of late apoptosis; and (iii) the appearance of polyploid cells after photon irradiation could predict the Relative Biological Efficiency(4) to carbon ions. This large collection of data should increase our knowledge in glioblastoma radiobiology in order to better understand, and to later individualize, appropriate radiotherapy treatment for patients who are good candidates.
authors: Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Faculté Médecine Lyon-Sud, Université de Lyon, Université Lyon1, 69921 Oullins, France.
authors: S
authors: S
authors: Ferrandon
authors: Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Faculté Médecine Lyon-Sud, Université de Lyon, Université Lyon1, 69921 Oullins, France; Départment de Radiothérapie, Institut de Cancérologie Lucien Neuwirth, 42271 St Priest-en-Jarez, France.
authors: N
authors: N
authors: Magné
authors: Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Faculté Médecine Lyon-Sud, Université de Lyon, Université Lyon1, 69921 Oullins, France.
authors: P
authors: P
authors: Battiston-Montagne
authors: Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Faculté Médecine Lyon-Sud, Université de Lyon, Université Lyon1, 69921 Oullins, France.
authors: N-H
authors: NH
authors: Hau-Desbat
authors: Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Faculté Médecine Lyon-Sud, Université de Lyon, Université Lyon1, 69921 Oullins, France.
authors: O
authors: O
authors: Diaz
authors: IPNL-LIRIS-CNRS-IN2P3, 69622 Villeurbanne, France.
authors: M
authors: M
authors: Beuve
authors: IPNL-LIRIS-CNRS-IN2P3, 69622 Villeurbanne, France.
authors: J
authors: J
authors: Constanzo
authors: Service de Radiothérapie, Hôpital du Val de Grâce, 75230 Paris, France.
authors: C
authors: C
authors: Chargari
authors: Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Faculté Médecine Lyon-Sud, Université de Lyon, Université Lyon1, 69921 Oullins, France; Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, 69495 Pierre-Bénite, France.
authors: D
authors: D
authors: Poncet
authors: Centre Jean Perrin, Laboratoire de Radio-Oncologie Expérimentale, Clermont Université, EA7283 CREaT, Université d'Auvergne, 63011 Clermont-Ferrand, France.
authors: E
authors: E
authors: Chautard
authors: Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Faculté Médecine Lyon-Sud, Université de Lyon, Université Lyon1, 69921 Oullins, France; Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, 69495 Pierre-Bénite, France.
authors: D
authors: D
authors: Ardail
authors: Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Faculté Médecine Lyon-Sud, Université de Lyon, Université Lyon1, 69921 Oullins, France; Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, 69495 Pierre-Bénite, France.
authors: G
authors: G
authors: Alphonse
authors: Laboratoire de Radiobiologie Cellulaire et Moléculaire, EMR3738, Faculté Médecine Lyon-Sud, Université de Lyon, Université Lyon1, 69921 Oullins, France; Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, 69495 Pierre-Bénite, France. Electronic address: claire.rodriguez-lafrasse@univ-lyon1.fr.
authors: C
authors: C
authors: Rodriguez-Lafrasse
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D002518:Ceramides / Q000378:metabolism; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints / Q000528:radiation effects; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D063193:Heavy Ion Radiotherapy; D006801:Humans; D007700:Kinetics; D008938:Mitosis / Q000528:radiation effects; D017785:Photons; D011836:Radiation Tolerance; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D002518:Ceramides; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
keywords: Carbon beam; Glioblastoma; Photon irradiation; Predictive marker; RBE