Nonviral gene delivery systems are considered to be a safe alternative to the viral system used in gene therapy. Although polyethylenimine (PEI) is among the most promising gene-carrier candidates for efficient nonviral gene delivery, safety concerns regarding its toxicity remain challenging. | Turkish Journal of Biology Turk J Biol (2014) 38: 380-387 © TÜBİTAK doi: Research Article Evaluation of genotoxicity and cytotoxicity induced by different molecular weights of polyethylenimine/DNA nanoparticles 1 2 3,4 1,4, Leila GHOLAMI , Hamid Reza SADEGHNIA , Majid DARROUDI , Reza KAZEMI OSKUEE * 1 Targeted Drug Delivery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 2 Pharmacological Research Center of Medicinal Plants, Department of Pharmacology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 3 Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 4 Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Received: Accepted: Published Online: Printed: Abstract: Nonviral gene delivery systems are considered to be a safe alternative to the viral system used in gene therapy. Although polyethylenimine (PEI) is among the most promising gene-carrier candidates for efficient nonviral gene delivery, safety concerns regarding its toxicity remain challenging. The aim of this study was to evaluate the less considered aspects of toxicity including genotoxicity effects of branched PEI with different molecular weights (1800 Da, 25 kDa, 750 kDa). Neuro2A mammalian cells were cultured in DMEM with 10% FBS and exposed to PEI/DNA complexes at different polymer/DNA ratios (known as the C/P ratio). To evaluate metabolic activities and genotoxicity, the treated cells were subjected to MTT and comet assays, respectively. Intracellular reactive oxygen species were also determined by using the fluorescent dye dichlorofluorescin diacetate. Concentration with relation to toxicity, genotoxicity, and ROS production was observed in Neuro2A cells treated with PEI/DNA nanoparticles. The difference among toxicities induced by different .