Resistance mechanisms in murine tumors with acquired multidrug resistance. 1992

M Volm, and T Efferth, and J Mattern, and E W Pommerenke
Department of Experimental Pathology, German Cancer Research Center, Heidelberg.

Mechanisms of multidrug resistance were studied in murine leukemia (L 1210) and sarcoma (Sa 180) tumors after pretreatment with anthracyclines in vivo. Despite identical pretreatment protocols, a considerable difference in the level of resistance between L 1210 and Sa 180 tumors was noted (for doxorubicin: 45-fold versus 340-fold; for daunorubicin: 51-fold versus 275-fold). However, no difference in mdr 1 gene-amplification and the overexpression of mdr 1-RNA or P-glycoprotein was demonstrated. None of these parameters did increase by further treatment with a higher concentration of anthracyclines. Resistant sublines of Sa 180 revealed an overexpression of glutathione S-transferase-pi (GST-pi) in comparison to the parental line, whereas in sensitive and resistant sublines of L 1210 tumors the expression of GST-pi was similar. In order to study whether trifluoperazine can reverse the P-glycoprotein mediated component of multidrug resistance, trifluoperazine and doxorubicin were tested in vitro in L 1210 and Sa 180 cells. In contrast to the complete reversal of resistance in L 1210 tumors, resistance in Sa 180 was only partly circumvented. However, by buthionine sulfoximine treatment, the toxicity of multidrug resistant Sa 180 tumors could be increased. It was possible to reverse the resistance of Sa 180 tumors completely by trifluoperazine plus buthionine sulfoximine. Thus, multidrug-resistant Sa 180 tumors express different defense mechanisms whereas L 1210 tumors express only one defense mechanism (P-glycoprotein).

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D007939 Leukemia L1210 An experimental LYMPHOCYTIC LEUKEMIA of mice. Leukemia L 1210,L 1210, Leukemia,L1210, 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
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
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D012510 Sarcoma 180 An experimental sarcoma of mice. Sarcoma 180, Crocker,Crocker Sarcoma 180
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
D015139 Blotting, Southern A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES. Southern Blotting,Blot, Southern,Southern Blot
D015152 Blotting, Northern Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES. Northern Blotting,Blot, Northern,Northern Blot,Blots, Northern,Blottings, Northern,Northern Blots,Northern Blottings
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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