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1.6 BIOLOGICAL SCIENCES
Polyamidoamine (PAMAM) dendrimers elicit systematically variable cyto- and eco-toxic responses, promising the basis for structure activity relationships governing nanotoxicological responses. Increased production of intracellular reactive oxygen species (ROS), genotoxicity and apoptosis due to in-vitro exposure of hepatocellular carcinoma cells to dendrimer generations G-4, G-5 and G-6 is demonstrated. A generation dependent increase in ROS and genotoxicity was observed, consistent with our previous studies. The responses correlate well with the number of surface amino groups per generation. Although ROS production initially increases approximately linearly, it saturates at higher doses. Notably, normalised to molar dose of surface amino groups, the dose-dependent ROS production for different generations overlap exactly, indicating that the response is due to these functional units. The percentage tail DNA formation is related to the generation and dose dependent production of intracellular ROS, at low levels. At the higher ROS levels, increased DNA damage is associated with the onset of necrosis.
Naha, P., Byrne, H.J. Generation of intracellular reactive oxygen species and genotoxicity effect to exposure of nanosized polyamidoamine (PAMAM) dendrimers in PLHC-1 cells in vitro, Aquatic Toxicology, Volumes 132–133, 15 May 2013, Pages 61-72, ISSN 0166-445X, doi:10.1016/j.aquatox.2013.01.020