Comparative studies on the genotoxicity and cytotoxicity of polymeric gene carriers polyethylenimine (PEI) and polyamidoamine (PAMAM) dendrimer in Jurkat T-cells.
A safe alternative to the viral system used in gene therapy is a nonviral gene delivery system. Although polyethylenimine (PEI) and polyamidoamine (PAMAM) dendrimer are among the most promising gene-carrier candidates for efficient nonviral gene delivery, safety concerns regarding their toxicity remain. The aim of this study was to scrutinize the underlying mechanism of the cytotoxicity and genotoxicity of PEI (25 kDa) and PAMAM (G4). To our knowledge, this is the first study to explore the genotoxic effect of polymeric gene carriers. To evaluate cell death by PEI and PAMAM, we performed propidium-iodide staining and lactate-dehydrogenase release assays. The genotoxicity of the polymers was measured by comet assay and cytokinesis-block micronucleus assay. PEI- and PAMAM-treated groups induced both necrotic and apoptotic cell death. In the comet assay and micronuclei formation, significant increases in DNA damage were observed in both treatments. We conclude that PEI and PAMAM dendrimer can induce not only a relatively weak apoptotic and a strong necrotic effect, but also a moderate genotoxic effect.
Choi
Young Joo
YJ
School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea.
Kang
Su Jin
SJ
Kim
Yang Jee
YJ
Lim
Yong-Beom
YB
Chung
Hai Won
HW
D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D050091:Dendrimers / Q000633:toxicity*; D004337:Drug Carriers / Q000633:toxicity*; D018014:Gene Transfer Techniques; D006801:Humans; D007097:Imines / Q000633:toxicity*; D019169:Jurkat Cells; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D015394:Molecular Structure; D009336:Necrosis; D011095:Polyethylenes / Q000633:toxicity*
D050091:Dendrimers; D004337:Drug Carriers; D007097:Imines; C104700:PAMAM Starburst; D011095:Polyethylenes; C505405:poly(ethylene imine)