title: Nuclear transport as an ultimate step of multidrug resistance.
abstract: Adriamycin (ADM) incorporation into nuclei of whole multidrug resistant (MDR) CEM cells is lower than into sensitive ones (S), that is mostly thought to be the consequence of a decrease of drug related to the activity of the multidrug resistance plasma membrane protein P 170. Isolated nuclei of the lymphoblastic tumor cell line CEM, which structures were controlled by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and confocal microscopy, where incubated with 10(-6) mole/l of ADM. Incorporation into DNA was quantified by spectrofluorimetry. It was lower and slower into MDR nuclei than into S ones. Different modulators of active transport influence drug transfer into S nuclei and had no effect in MDR nuclei. The nuclear transfer into S nuclei appeared divided into two components: one was decreased by WGA, increased by cytosolic factors and an other part was purely passive in an identical intensity to MDR nuclei. Resistance of MDR nuclei seemed indebt to a defect, in these cells, of factors that mediate and/or activate nuclear transport of drug.
authors.affiliation: EA 2063, IFR 53 Biomolécules, UFR Pharmacie, Reims, France. héléne.bobichon@univ-reims.fr
authors.forename: H
authors.initials: H
authors.lastname: Bobichon
authors.forename: L
authors.initials: L
authors.lastname: Cailleret
authors.forename: D
authors.initials: D
authors.lastname: Ploton
authors.forename: R
authors.initials: R
authors.lastname: Belhoussine
authors.forename: J C
authors.initials: JC
authors.lastname: Jardillier
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D001692:Biological Transport; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D004317:Doxorubicin / Q000493:pharmacokinetics; D018432:Drug Resistance, Multiple; D006801:Humans; D007945:Leukemia, Lymphoid / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018613:Microscopy, Confocal; D017348:Microscopy, Electron, Scanning Transmission; D009685:Nuclear Envelope / Q000378:metabolism; D013194:Staining and Labeling; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin