title: Cytotoxicity and genotoxicity of cationic phosphorus-containing dendrimers.
abstract: Cationic phosphorus-containing dendrimers (CPDs) are a class of highly-branched polymers with potential medical relevance. However, little is known about CPD modes of interactions with cell and its components, including DNA. In the present work we investigated cytotoxicity and genotoxicity of CPDs generation 3 and 4 (CPD G3 and CPD G4) in human mononuclear blood cells, A549 human cancer cells and human gingival fibroblasts (HGFs). CPD G3 and CPD G4 at concentrations up to 10 μM induced a concentration-dependent decrease in cell viability as assessed by flow cytometry. Both compounds did not induce breaks in isolated DNA as evaluated by the plasmid relaxation assay but they induced DNA cross-links in the cells, as examined by comet assay. CPD G3 and 4 induced slight perturbations in the cell cycle leading to a decrease in the G2/M cell population accompanied by an increase in the S cell population. Upon treatment with CPDs, the cells showed changes in their morphology, including loss of cell attachment, disruption of cell membrane and nucleus condensation. Our results indicate that CPD G3 and G4 are cytotoxic and genotoxic for the assorted human cells. Therefore, CPDs may form stable complexes with DNA and interfere with cellular processes.
authors.affiliation: Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland. pgomulak@biol.uni.lodz.pl
authors.forename: P
authors.initials: P
authors.lastname: Gomulak
authors.forename: B
authors.initials: B
authors.lastname: Klajnert
authors.forename: M
authors.initials: M
authors.lastname: Bryszewska
authors.forename: J P
authors.initials: JP
authors.lastname: Majoral
authors.forename: A M
authors.initials: AM
authors.lastname: Caminade
authors.forename: J
authors.initials: J
authors.lastname: Blasiak
mesh_terms: D002412:Cations / Q000737:chemistry; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D010758:Phosphorus / Q000737:chemistry*
chemical_list: D002412:Cations; D050091:Dendrimers; D010758:Phosphorus