Archives of Toxicology

, Volume 85, Issue 12, pp 1575–1588 | Cite as

Variation in the internalization of differently sized nanoparticles induces different DNA-damaging effects on a macrophage cell line

  • Mingyi Zhang
  • Juan Li
  • Gengmei XingEmail author
  • Rui He
  • Wei Li
  • Yan Song
  • Haili Guo
Molecular Toxicology


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 500 nm. 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.


DNA damage Entry pathway Carboxylated nanoparticles Size-dependency RAW 264.7 



We are thankful for the funding supports from NSFC (10875136), the 973 program (2007CB935604, 2009CB930204, 2011CB933400), CAS (KJC-NM2007), and CAS Knowledge Innovation Program. We would like to acknowledge the scientists and the fellow research members at the Beijing Synchrotron Radiation Facility in helping with the XPS.

Supplementary material

204_2011_725_MOESM1_ESM.pdf (129 kb)
Supplementary material 1 (PDF 128 kb)


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Mingyi Zhang
    • 1
  • Juan Li
    • 1
  • Gengmei Xing
    • 1
    Email author
  • Rui He
    • 2
  • Wei Li
    • 1
  • Yan Song
    • 1
  • Haili Guo
    • 1
  1. 1.Lab for Bio-Environmental Effects of Nanomaterials and Nanosafety, Institute of High Energy PhysicsChinese Academy of ScienceBeijingChina
  2. 2.Research Center of Biomedicine and HealthHangzhou Normal UniversityHangzhouChina

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