Characteristics of five human tumor cell lines and sublines resistant to cis-diamminedichloroplatinum(II)
| Autor: | Sylvia A. Holden, Terence S. Herman, Timothy Korbut, Vrinda Khandekar, Enrique Alvarez Sotomayor, Beverly A. Teicher, Kristina W. Rosbe, Terrence W. Brann, Emil Frei |
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| Rok vydání: | 1991 |
| Předmět: |
Cancer Research
Lung Neoplasms Organoplatinum Compounds Cell Survival Drug Resistance Breast Neoplasms ThioTEPA Biology Adenocarcinoma Carboplatin chemistry.chemical_compound Neoplasms medicine Tumor Cells Cultured Humans Sulfhydryl Compounds Carcinoma Small Cell Melanoma Glutathione Transferase Platinum Cloning Chlorambucil DNA Molecular biology female genital diseases and pregnancy complications In vitro Oncology chemistry Mechanism of action Cell culture Immunology Carcinoma Squamous Cell medicine.symptom Cisplatin medicine.drug |
| Zdroj: | International journal of cancer. 47(2) |
| ISSN: | 0020-7136 |
| Popis: | In order to study the mechanisms responsible for resistance to CDDP, 5 human tumor cell lines were made resistant to CDDP by repeated in vitro exposures. After cloning it was found that the cell lines developed were between 3.3-fold and 17-fold more resistant to CDDP than the parental cell lines at the IC90. These lines were also resistant to carboplatin and tetraplatin; however, resistance to tetraplatin was lower than to the other platinum complexes. Sensitivity was also assessed to Adria, MTX, 5-FU, chlorambucil, 4-HC, 4-HIF, BCNU, Thiotepa, HN2, Mito C and L-PAM, and no consistent cross-resistance was observed. As compared with the parental lines, non-protein sulfhydryl content was elevated in 3 resistant lines, and protein sulfhydryl was elevated in all 5 lines, as was glutathione-S-transferase activity. Measurements of platinum in whole cells and nuclei after exposure of the cultures to 25 microM CDDP for either 1 or 6 hr showed that nuclear levels reflected those in whole cells and that, per mg protein, platinum levels were lower in resistant cells at both time points. Formation of DNA cross-links, determined by alkaline elution, was lower in resistant cell lines than in parental cell lines, but did not correlate with the absolute cell kill observed. These results indicate that cellular resistance to CDDP often involves decreases in drug accumulation and increases in protein sulfhydryl content. Possible strategies for overcoming these mechanisms are discussed. |
| Databáze: | OpenAIRE |
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