In vitro split-dose recovery of glioblastoma multiforme. 1993

A Taghian, and D Gioioso, and W Budach, and H Suit
Edwin L. Steele Laboratory of Radiation Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston 02114.

Glioblastoma multiforme is among the most clinically resistant tumors to radiation. This resistance may be due to several different factors, such as a low intrinsic radiation sensitivity, a high recovery capacity, an increased number of clonogens, and a high hypoxic fraction. Previously, we have demonstrated a very wide range of intrinsic radiation sensitivities of cells of glioblastoma multiforme cell lines in vitro after single-dose irradiation. That is, the cells of some glioblastoma multiforme cell lines were quite sensitive, while for others the sensitivity of glioblastoma multiforme was among the lower range of sensitivities reported in the literature. This finding indicates that inherent cellular radiation sensitivity is not the sole determinant of the in vivo response of glioblastoma multiforme tumors. In this report, we evaluate the role of split-dose recovery determined in vitro in relation to the poor clinical outcome of glioblastoma multiforme. Cells of seven early-passage glioblastoma multiforme cell lines and six cell lines derived from tumors of a type frequently treated successfully (two squamous cell carcinomas of head and neck, three breast cancers, and one low-grade astrocytoma cell line) were studied. The in vitro split-dose recovery has been measured using colony formation as an end point. The cells were maintained at 37 degrees C for a period of 6 h between the doses of radiation. Results are presented in terms of a recovery ratio: the ratio of the mean inactivation dose of split-dose radiation to that of single-dose radiation. The data show significantly higher recovery ratios for glioblastoma multiforme than for the other types of histology; however, glioblastoma multiforme showed a wide range of recovery ratios, varying from 1.12 to 2.02. This indicates that cells of some glioblastoma multiforme cell lines exhibit minimal split-dose recovery. No correlation was found between the recovery ratio and the intrinsic radiation sensitivity of the cell lines studied. From these data, we conclude that the recovery capacity may not be the major determinant of the clinical radiation resistance of some glioblastoma multiforme.

UI MeSH Term Description Entries
D011831 Radiation Genetics A subdiscipline of genetics that studies RADIATION EFFECTS on the components and processes of biological inheritance. Genetics, Radiation
D011836 Radiation Tolerance The ability of some cells or tissues to survive lethal doses of IONIZING RADIATION. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS. Radiation Sensitivity,Radiosensitivity,Sensitivity, Radiation,Tolerance, Radiation,Radiation Sensitivities,Radiation Tolerances,Radiosensitivities,Sensitivities, Radiation,Tolerances, Radiation
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D004273 DNA, Neoplasm DNA present in neoplastic tissue. Neoplasm DNA
D004307 Dose-Response Relationship, Radiation The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation. Dose Response Relationship, Radiation,Dose-Response Relationships, Radiation,Radiation Dose-Response Relationship,Radiation Dose-Response Relationships,Relationship, Radiation Dose-Response,Relationships, Radiation Dose-Response
D005909 Glioblastoma A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. Astrocytoma, Grade IV,Giant Cell Glioblastoma,Glioblastoma Multiforme,Astrocytomas, Grade IV,Giant Cell Glioblastomas,Glioblastoma, Giant Cell,Glioblastomas,Glioblastomas, Giant Cell,Grade IV Astrocytoma,Grade IV Astrocytomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured

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