ABSTRACT
An experimental intracerebral C6 glioma model in immunosuppressed female hairless rats has been developed. The rate of tumor uptake was evaluated by magnetic resonance imaging (MRI), using specific sequences without gadolinium enhancement. Twenty-four hours before intracerebral transplantation, a control cranial MRI was carried out and rats underwent a total body irradiation (TBI). MRI was repeated seven days after transplantation in order to monitor tumor uptake. Then, twelve days after transplantation, tumors were treated with two different protocols of radiotherapy: 3 Gy during 5 days or 0.7 Gy three times a day during 5 days (ultra fractionation). A third MRI was performed 21 days after intracerebral transplantation. Eventually, all the rats were sacrificed and histological analysis of the tumors was performed. Our results show that TBI efficiently increases the rate of tumor uptake. Thereafter, tumor formation and growth as well as the efficiency of a therapy (radiotherapy in our case) can be monitored with MRI (without gadolinium enhancement). Treatment of C6 glioma tumors with ultrafractionation was a marked improvement compared to a more traditional radiotherapy treatment. We developed a model that is useful for the study of new glioma treatment. We also obtained promising preliminary results when using ultra fractionation radiotherapy.
Subject(s)
Brain Neoplasms/pathology , Brain Neoplasms/radiotherapy , Glioblastoma/pathology , Glioblastoma/radiotherapy , Animals , Cell Division/radiation effects , Disease Models, Animal , Dose Fractionation, Radiation , Female , Magnetic Resonance Imaging , Neoplasm Transplantation , Rats , Whole-Body IrradiationABSTRACT
Malignant gliomas display aggressive local behavior and are not cured by existing therapy. Some cell lines that are considered radioresistant respond to low radiation doses (<1 Gy) with increased cell killing (low-dose hypersensitivity). In our study, 4 of 5 human glioma cell lines exhibited significant X-ray sensitivity at doses below 1 Gy. The surviving fractions (SFs) obtained at 0.7 and/or 0.8 Gy were comparable to those at 1.5 Gy. Low-dose hypersensitivity was evident when irradiation was combined with etoposide treatment. Repeated irradiation with low doses was markedly more effective than irradiation with single, biologically equivalent doses in decreasing SFs, inhibiting xenograft tumor growth in mice. All experiments were conducted with an accelerator used in clinics, establishing that low-dose hypersensitivity was present following megavoltage X-irradiation. Thus, repeated low-dose irradiation (ultrafractionation) could greatly improve the effectiveness of radiotherapy of gliomas and could allow safe treatment of patients with cumulative doses greater than 60 Gy.
Subject(s)
Brain Neoplasms/radiotherapy , Glioma/radiotherapy , Animals , Cell Survival , Dose-Response Relationship, Radiation , Etoposide/pharmacology , Female , Humans , Mice , Neoplasm Transplantation , Radiation Tolerance , Time Factors , Tumor Cells, CulturedABSTRACT
We investigated the production of interleukin 6 (IL-6) by a radioresistant human glioblastoma cell line G5 after single radiation events of 3, 6 and 9 Gy. The total cell number and IL-6 concentration in culture supernatant were assessed 24-96 h after irradiation. The radiation impeded or stopped G5 cell growth in a dose-dependent manner, but unexpectedly did not affect the IL-6 concentration in cell culture media that increased in the same range as in non-irradiated cultures. Furthermore, using flow cytometry, we found that the IL-6 positive cells expansion was unaffected by radiation. These findings suggested that this small (about 1%) fraction of G5 cells, constitutively producing IL-6, is highly radioresistant.
