Response of sensitive and resistant IgM immunocytomas to cis-diamminedichloroplatinum (II) does not correlate with the platination level or with the formation or removal of DNA adducts
| Autor: | P. A. Steerenberg, A.M.J. Fichtinger-Schepman, Cornelis P. J. Vendrik, Gerard de Groot, W. H. de Jong, Wilhelmina C. M. van Dijk-Knijnenburg, Geert Frits Berends, Anke C. E. van der Minnen |
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| Rok vydání: | 1997 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty medicine.medical_treatment chemistry.chemical_element Toxicology Adduct chemistry.chemical_compound DNA Adducts medicine Animals Pharmacology (medical) Pharmacology Cisplatin Kidney Chemotherapy Cis diamminedichloroplatinum ii Chemistry Molecular biology Leukemia Lymphocytic Chronic B-Cell female genital diseases and pregnancy complications Rats medicine.anatomical_structure Oncology Immunoglobulin M Cell culture Drug Resistance Neoplasm Platinum DNA Neoplasm Transplantation medicine.drug |
| Zdroj: | Cancer chemotherapy and pharmacology. 39(6) |
| ISSN: | 0344-5704 |
| Popis: | An IgM immunocytoma cell line sensitive to cis-diamminedichloroplatinum(II) (CDDP) and a subline with acquired resistance were grown in LOU/M rats. In a previous study with such rats that had been treated with a high dose of CDDP (10 mg/kg) the tumors did not show differences in cellular platinum content or DNA-adduct levels, either immediately after treatment or 24 h later. Recently, this high dose was found to overcome resistance. Therefore, the study was repeated with a 10-fold lower dose (1 mg/kg, i.v.). At 1 and 24 h after treatment, tumor and kidney tissue were assayed for cellular platinum (atomic absorption spectroscopy, AAS) and DNA platination (immunochemical detection of the four CDDP-DNA adducts). The results were compared with previous data. All tissues showed a linear response to dose with regard to platinum uptake as well as adduct formation, with no quantitative difference being seen between the tumors. Also the relative occurrence of the four adducts was very similar. Between 1 and 24 h, in tumors a substantial decrease occurred in both platinum content and adduct level; the kidneys showed little reduction, if any. At the lower CDDP dose a somewhat larger loss of platinum and removal of DNA adducts was observed for the resistant tumor, but these differences could be explained by “dilution”, as this tumor continues to grow after low-dose treatment (about 20% within 24 h). Since the strong difference observed between the tumors in sensitivity to CDDP cannot be attributed to differences in CDDP uptake, efficiency of adduct formation, or repair capability, other mechanisms are held responsible. |
| Databáze: | OpenAIRE |
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