title: Dequalinium vesicles form stable complexes with plasmid DNA which are protected from DNase attack.
abstract: Upon sonication, the antimicrobial and antineoplastic compound dequalinium forms vesicles (DQAsomes, Weissig et al., 1998). Dequalinium (1,1'-(1,10-decamethylene-bis-[aminoquinaldinium])-chloride) was shown to be a fluorophore with an emission maximum at 366 nm. Addition of DNA results in a characteristic quenching of its intrinsic fluorescence. After density gradient centrifugation a band of dequalinium (DQA) tightly associated with DNA is located between the DNA and DQA bands. DQA/DNA-complexes containing plasmid DNA at a molar ratio of DQA/DNA 6:1 are completely protected against DNase activity. Addition of negatively-charged lipids release intact DNA in the same manner as from cationic lipid/DNA complexes. As regards biological effects, DQAsomes show a differential cytotoxicity for normal and sarcoma cell lines. In vitro incubation with fluorescein-labeled oligodeoxynucleotides (5'-fluorescein-[GATC]5) showed an increased uptake of the tagged oligodeoxynucleotide if complexed with dequalinium. We hypothesize that the DQA/DNA complexes are well-suited for 'DQAsomal gene transfer' in vitro and in vivo. Noteworthy, they display an intrinsic antitumor activity manifested by differential cytotoxicity for normal and sarcoma cells.
authors.affiliation: Institute of Physiological Chemistry, Martin-Luther-University Halle, Halle/Saale, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Lasch
authors.forename: A
authors.initials: A
authors.lastname: Meye
authors.forename: H
authors.initials: H
authors.lastname: Taubert
authors.forename: R
authors.initials: R
authors.lastname: Koelsch
authors.forename: J
authors.initials: J
authors.lastname: Mansa-ard
authors.forename: V
authors.initials: V
authors.lastname: Weissig
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D003851:Deoxyribonucleases / Q000378:metabolism*; D003868:Dequalinium / Q000737:chemistry* / Q000494:pharmacology; D005614:Freeze Fracturing; D006801:Humans; D008854:Microscopy, Electron; D010316:Particle Size; D010957:Plasmids; D014407:Tumor Cells, Cultured
chemical_list: D004247:DNA; D003868:Dequalinium; D003851:Deoxyribonucleases