caa a22 4500 445853174 CHVBK 20180317145419.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s00204-011-0725-y doi (NATIONALLICENCE)springer-10.1007/s00204-011-0725-y Variation in the internalization of differently sized nanoparticles induces different DNA-damaging effects on a macrophage cell line [Elektronische Daten] [Mingyi Zhang, Juan Li, Gengmei Xing, Rui He, Wei Li, Yan Song, Haili Guo] Although researchers have expended considerable effort on studying the cytotoxicity of nanomaterials, it is possible that there has been insufficient attention paid to their genotoxic potential. Here, we describe a test model that we have developed to evaluate the DNA-damaging effects of negatively charged nanoparticles of different sizes. We compared the DNA damaging effect induced by nanoparticles of various sizes and found that the effect is closely associated with the internalization pattern of the particles. Macrophage cell line RAW 264.7 cells were incubated with carboxylated polystyrene beads (COOH-PBs) ranging in size from 30 to 500nm. Size-dependent DNA damage was detected, and the lesion induced by two carboxylated fullerene particles confirmed this observation. Confocal microscopy revealed that the entry pathways of these COOH-PBs shifted from direct penetration to endocytosis with increasing particle size, followed by changes in subcellular localization. Subsequent deposition of 30-nm COOH-PBs in the cytosol led to a reduction of Zn2+ and Mg2+ content in the nucleus and an increased p53 level in the whole cell rather than in nucleus, while localization of 50- and 100-nm COOH-PBs in acidic vesicles induced p53 accumulation in both types of extracts. Based on these results, we assume that the damage resulted from a disruption of the balance between DNA damage and repair. Springer-Verlag, 2011 DNA damage nationallicence Entry pathway nationallicence Carboxylated nanoparticles nationallicence Size-dependency nationallicence RAW 264.7 nationallicence Zhang Mingyi Lab for Bio-Environmental Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science, 10049, Beijing, China aut Li Juan Lab for Bio-Environmental Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science, 10049, Beijing, China aut Xing Gengmei Lab for Bio-Environmental Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science, 10049, Beijing, China aut He Rui Research Center of Biomedicine and Health, Hangzhou Normal University, 310012, Hangzhou, China aut Li Wei Lab for Bio-Environmental Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science, 10049, Beijing, China aut Song Yan Lab for Bio-Environmental Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science, 10049, Beijing, China aut Guo Haili Lab for Bio-Environmental Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science, 10049, Beijing, China aut Archives of Toxicology Springer-Verlag 85/12(2011-12-01), 1575-1588 0340-5761 85:12<1575 2011 85 204 https://doi.org/10.1007/s00204-011-0725-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-011-0725-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhang Mingyi Lab for Bio-Environmental Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science, 10049, Beijing, China aut NATIONALLICENCE 700 1- Li Juan Lab for Bio-Environmental Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science, 10049, Beijing, China aut NATIONALLICENCE 700 1- Xing Gengmei Lab for Bio-Environmental Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science, 10049, Beijing, China aut NATIONALLICENCE 700 1- He Rui Research Center of Biomedicine and Health, Hangzhou Normal University, 310012, Hangzhou, China aut NATIONALLICENCE 700 1- Li Wei Lab for Bio-Environmental Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science, 10049, Beijing, China aut NATIONALLICENCE 700 1- Song Yan Lab for Bio-Environmental Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science, 10049, Beijing, China aut NATIONALLICENCE 700 1- Guo Haili Lab for Bio-Environmental Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Science, 10049, Beijing, China aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/12(2011-12-01), 1575-1588 0340-5761 85:12<1575 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer