Abstract 5657: Polyamidoamine dendrimers induce epigenetic changes in cultured normal and malignant human lung epithelial cells.

Abstract

Abstract Dendrimers constitute structurally well-defined nanomaterials that are potentially useful for a vast range of biomedical applications, including targeted cancer therapy. Polyamidoamine (PAMAM) dendrimers are a relatively unexplored material subclass from consideration of low-dose studies of toxicological and biological effects, including epigenetic changes that may link to altered cell differentiation and risk of transformation. The present study assessed cell viability, histone modifications, genome-wide DNA methylation and gene expression changes in primary human bronchial epithelial cells (PBEC) and the human alveolar epithelial cell line A549 following exposure to 4th generation PAMAM dendrimers with hydroxyl (-OH) or amino (-NH2) terminating groups. The preliminary results show that these PAMAMs can regulate DNA methylation and histone modification at micromolar levels without significant effect on cell viability (lactate dehydrogenase assay). Specific changes in DNA methylation patterns implicated inflammation-related genes, although with different results in the two model systems. The results imply epigenetic regulation of gene expression by PAMAMs, and follow up work now investigates this hypothesis. Close attention to safety issues is of paramount importance for the sustainable development of the nanotechnologies, especially for biomedical applications, and the present data may shed light on potential long-term/low-dose effects of engineered nanomaterials. Citation Format: Pekka J. Kohonen, Neus T. Feliu, Lena Palmberg, Hanna L. Karlsson, Annika E. Wallberg, Roland C. Grafström, Bengt Fadeel. Polyamidoamine dendrimers induce epigenetic changes in cultured normal and malignant human lung epithelial cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5657. doi:10.1158/1538-7445.AM2013-5657