title: Resistance of in vitro grown IgM immunocytoma cells to cis-diamminedichloroplatinum (II) (cis-DDP) and cross-resistance to other DNA interacting drugs.
abstract: Previously, we reported on the resistance to cis-diamminedichloroplatinum(II) (cis-DDP) of tumor cells in IgM immunocytoma tumors. In vitro cell lines were established, from tumors both sensitive and resistant to cis-DDP. The cultured cells obtained from the parent tumor were designated IgM-I, and those from a cis-DDP resistant tumor IgM/cDDP. In vitro dose response studies showed a difference in cis-DDP sensitivity with a resistance factor of approximately 20 at a relative survival of the tumor cells of 50 percent. The resistance factor was determined both in an assay with continuous cis-DDP exposure for 72 h, and in a clonogenic assay after an exposure for 1 h to various dosages of cis-DDP. The IgM/cDDP cells showed cross-resistance, in vitro and in vivo, to the currently used cis-DDP analogs carboplatin (CBDCA or JM8) and iproplatin (CHIP or JM9). Cross-resistance was also observed against the recently developed platinum(IV) compound tetraplatin. In addition, the cell line IgM/cDDP was resistant to other drugs interacting with DNA, such as doxorubicin (DXR), mitomycin C (MMC) and melphalan (L-PAM). For two non DNA-interacting drugs, vincristine (VCR), a mitosis inhibitor, and VP-16, a topoisomerase inhibitor, both cell lines were equally sensitive.
authors.affiliation: Laboratory for Pathology, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
authors.forename: C P
authors.initials: CP
authors.lastname: Vendrik
authors.forename: W H
authors.initials: WH
authors.lastname: de Jong
authors.forename: A C
authors.initials: AC
authors.lastname: Van der Minnen
authors.forename: A M
authors.initials: AM
authors.lastname: Fichtinger-Schepman
authors.forename: P A
authors.initials: PA
authors.lastname: Steerenberg
authors.forename: J H
authors.initials: JH
authors.lastname: Schornagel
mesh_terms: D002945:Cisplatin / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000187:drug effects; D004351:Drug Resistance; D007075:Immunoglobulin M; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology
chemical_list: D004273:DNA, Neoplasm; D007075:Immunoglobulin M; D002945:Cisplatin