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 concentrationdependent
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.
Keywords: A549 cells, apoptosis, cationic phosphorus-containing dendrimer, cell cycle, cell viability, comet assay, DNA damage, HGF
cells, human lymphocytes, morphology assay, plasmid relaxation assay
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Published on: 30 November, 2012
Page: [6233 - 6240]