Biomaterial Database

Glutathione manipulation and the radiosensitivity of human tumour and fibroblast cell lines. 1995

T Orta, and J J Eady, and J H Peacock, and G G Steel

Radiotherapy Research Unit, Institute of Cancer Research, Sutton, UK.

We have studied the role of glutathione (GSH) in determining radiation response in five human tumour and one human fibroblast cell line. GSH concentration was measured using the Tietze assay and compared with clonogenic survival following gamma-irradiation. No relationship between GSH concentration and aerobic radiosensitivity was observed. The addition of 10 mM extracellular cysteamine produced protection factors in all cell lines, ranging from 1.6 to 2.1, but had little influence on cellular GSH concentration. Depletion of GSH by buthionine sulphoximine (0.1 mM for 18 h) had negligible effect on cell survival, though moderate radiosensitization resulted from extreme GSH depletion after 30-min treatment with 1 mM dimethylfumarate. The degree of aerobic sensitization did not correlate with GSH levels. Irradiation under hypoxia produced oxygen enhancement ratios varying from 1.6 to 2.6, with no relationship to GSH content.

UI	MeSH Term	Description	Entries
D008717	Methionine Sulfoximine		Sulfoximine, Methionine
D009369	Neoplasms	New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.	Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
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
D005347	Fibroblasts	Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.	Fibroblast
D005978	Glutathione	A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.	Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
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
D019328	Buthionine Sulfoximine	A synthetic amino acid that depletes glutathione by irreversibly inhibiting gamma-glutamylcysteine synthetase. Inhibition of this enzyme is a critical step in glutathione biosynthesis. It has been shown to inhibit the proliferative response in human T-lymphocytes and inhibit macrophage activation. (J Biol Chem 1995;270(33):1945-7)	Sulfoximine, Buthionine