title: Complementary advantages of fluorescence and SIMS microscopies in the study of cellular localization of two new antitumor drugs.
abstract: Low light level fluorescence microscopy studies have been carried out on MCF7-P human mammary tumor cells to localize the intracellular distribution of two new anticancer drugs, Pazelliptine and Intoplicine, which are currently under clinical evaluation. These two molecules are thought to act at the nuclear level, through DNA topoisomerase interactions. Because fluorescence of these compounds appears strongly quenched by intercalation in double strand DNA, secondary ion mass spectrometry (SIMS) imaging was used to check the presence of the drugs in the nuclear compartment. In spite of chemical structure similitudes, pazelliptine and intoplicine appear to be distributed in quite different ways within the cells. Incubation for 1 and 24 hours also allowed us to bring to light strong differences in the distribution kinetics. Pazelliptine quickly enters into the nucleoli but is no longer present in the nucleus after 24 hours incubation. Intoplicine was not detected by fluorescence in the nucleus, however SIMS microscopy allowed us to show its accumulation within this cellular compartment as a function of time of exposure. This study shows the complementarity of fluorescence and SIMS microscopies.
authors.affiliation: INSERM U350, Institut Curie Recherche, Laboratoire Raymond Latarjet, Centre Universitaire, Orsay, France.
authors.forename: J L
authors.initials: JL
authors.lastname: Guerquin-Kern
authors.forename: M
authors.initials: M
authors.lastname: Coppey
authors.forename: D
authors.initials: D
authors.lastname: Carrez
authors.forename: A C
authors.initials: AC
authors.lastname: Brunet
authors.forename: C H
authors.initials: CH
authors.lastname: Nguyen
authors.forename: C
authors.initials: C
authors.lastname: Rivalle
authors.forename: G
authors.initials: G
authors.lastname: Slodzian
authors.forename: A
authors.initials: A
authors.lastname: Croisy
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics*; D007546:Isoquinolines / Q000493:pharmacokinetics*; D013058:Mass Spectrometry; D008856:Microscopy, Fluorescence; D011725:Pyridines / Q000493:pharmacokinetics*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D007546:Isoquinolines; D011725:Pyridines; C024256:pazelliptine; C081834:intoplicine