Influence of vinblastine on DNA parameters and multidrug resistance in renal cell carcinoma in vitro.
The purpose of this study was to investigate how the vinca alkaloid vinblastine influences DNA parameters and the mechanisms of multidrug resistance in renal cell carcinoma. After exposing cell cultures of human renal carcinoma to progressively increasing concentrations of vinblastine the cell lines were examined by flow cytometric DNA analysis to assess the S-phase and G2/M-phase fraction and by a modified MTT assay. It was shown that the exposed cells became P-glycoprotein-positive by staining the cells with a monoclonal antibody (JSB-1). The flow cytometric analysis revealed, with prolonged vinblastine exposure, correlated increases in the S-phase and G2/M-phase fractions (P = 0.0001). When vinblastine-free medium was used for culturing, the changed DNA characteristics returned to their original values. Comparing the DNA parameters with the IC50 (concentration when cell growth is inhibited by 50%) we found a strong correlation between these parameters (P = 0.0001). In conclusion, DNA analysis of long-term vinblastine exposure may provide insight into events leading to multidrug resistance. Furthermore, analysis of the DNA profile might also be an important investigation before planning therapy with vinblastine for renal cell carcinoma.
Domagk
D
D
Klinik für Urologie, Georg-August-Universität Göttingen, Germany.
Blüthner-Hässler
C
C
Kugler
A
A
Kallerhoff
M
M
Ringert
R H
RH
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D013778:Tetrazolium Salts; D013844:Thiazoles; D014747:Vinblastine; C022616:thiazolyl blue