title: Possible mechanism responsible for the acquisition of resistance to cis-diamminedichloroplatinum (II) by cultured human testicular seminoma cells.
abstract: OBJECTIVE
  We established a cis-diamminedichloroplatinum (II) (CDDP) resistant cell line and determined the mechanisms of CDDP resistance.
  
  
  METHODS
  The CDDP resistant cell line JKT/DDP was established from the highly metastatic human testicular seminoma cell line JKT-HM by long-term intermittent administration of low dose CDDP. Growth curves, CDDP sensitivity and intracellular CDDP concentrations were compared in JKT/DDP, the seminoma cell line JKT-1 and JKT-HM cells. Expression of the mRNA of MDR1, MRP, LRP and GST-pi was also compared.
  
  
  RESULTS
  The growth curve and doubling time of JKT/DDP were similar to those of JKT-1 and JKT-HM in culture without CDDP but different with CDDP added to the culture. Morphologically cytoplasm segmentation and chromatin aggregation in JKT-1 and JKT-HM were observed when CDDP was present, while JKT/DDP cells were spindle-shaped and showed cobblestone growth. The IC50 for CDDP determined by the collagen gel drop embedded drug sensitivity test showed that JKT/DDP was more resistant to CDDP than the other 2 cell lines. The expression of MDR1, MRP and GST-pi was higher than in JKT-1 or JKT-HM cells and the intracellular CDDP concentration was lower in JKT/DDP.
  
  
  CONCLUSIONS
  The JKT/DDP cell line acquired CDDP resistance by increased cytoplasmic CDDP metabolism.
authors.affiliation: Department of Urology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Fujii
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Jo
authors.forename: Keigo
authors.initials: K
authors.lastname: Kinugawa
authors.forename: Masato
authors.initials: M
authors.lastname: Fujisawa
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D018239:Seminoma / Q000188:drug therapy* / Q000473:pathology; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin