Biomaterial Database

Potentiation of mitomycin C cytotoxicity by glutathione depletion in a multi-drug resistant mouse leukemia cell line. 1992

B H Xu, and S V Singh

Mercy Cancer Center, Mercy Hospital of Pittsburgh, PA 15219.

This study was undertaken to elucidate the mechanism of cross-resistance to mitomycin C (MMC) in a multi-drug resistant mouse leukemia cell line (P388/R-84). The P388/R-84 cells were 6.2-fold more resistant to MMC as compared to the sensitive cells (P388/S). Since oxygen radical formation has been suggested to be important in MMC cytotoxicity, MMC-dependent peroxidation of membrane lipids (an index of oxygen radical formation) was compared in these cell lines. MMC-dependent lipid peroxidation was 2.56-fold higher using P388/S cell extract when compared to that of P388/R-84 cells. Depletion of cellular glutathione (GSH) levels in the resistant cells produced a 1.76-fold increase in MMC-dependent lipid peroxidation. MMC cytotoxicity was also increased significantly by GSH depletion in P388/R-84 cells. These results suggest that cellular resistance to MMC in P388/R-84 cells may, at least in part, be due to the reduced formation of oxyradicals in these cells.

UI	MeSH Term	Description	Entries
D007941	Leukemia P388	An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene.	P388D(1) Leukemia,P388, Leukemia
D004351	Drug Resistance	Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.	Resistance, Drug
D004354	Drug Screening Assays, Antitumor	Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.	Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
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
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
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
D015227	Lipid Peroxidation	Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor.	Lipid Peroxidations,Peroxidation, Lipid,Peroxidations, Lipid
D016685	Mitomycin	An antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional ALKYLATING AGENTS causing cross-linking of DNA and inhibition of DNA synthesis.	Mitomycin C,Ametycine,Mitocin-C,Mitomycin-C,Mutamycin,NSC-26980,Mitocin C,MitocinC,NSC 26980,NSC26980
D017382	Reactive Oxygen Species	Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.	Active Oxygen Species,Oxygen Radical,Oxygen Radicals,Pro-Oxidant,Reactive Oxygen Intermediates,Active Oxygen,Oxygen Species, Reactive,Pro-Oxidants,Oxygen, Active,Pro Oxidant,Pro Oxidants,Radical, Oxygen