Alternariol induces abnormal nuclear morphology and cell cycle arrest in murine RAW 264.7 macrophages

Toxicol Lett. 2013 May 10;219(1):8-17. doi: 10.1016/j.toxlet.2013.02.012. Epub 2013 Feb 27.


The mycotoxin alternariol (AOH), a frequent contaminant in fruit and cereal products, is known to induce DNA damage with subsequent cell cycle arrest. Here we elucidated the effects of AOH on stages of cell cycle progression using the RAW 264.7 macrophage model. AOH resulted in an accumulation of cells in the G2/M-phase (4N). Most cells exhibited a large G2 nucleus whereas numbers of true mitotic cells were reduced relative to control. Both cyclin B1 and p-cdc2 levels increased, while cyclin B1 remained in the cytoplasm; suggesting arrest in the G2/M transition point. Remarkably, after exposure to AOH for 24h, most of the cells exhibited abnormally shaped nuclei, as evidenced by partly divided nuclei, nuclear blebs, polyploidy and micronuclei (MN). AOH treatment also induced abnormal Aurora B bridges, suggesting that cytokinesis was interfered within cells undergoing karyokinesis. A minor part of the resultant G1 tetraploid (4N) cells re-entered the S-phase and progressed to 8N cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Cell Nucleus / drug effects*
  • Cell Nucleus / metabolism
  • Cell Nucleus / ultrastructure
  • Cell Nucleus Shape / drug effects
  • Cell Nucleus Size / drug effects
  • Flow Cytometry
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • Lactones / toxicity*
  • M Phase Cell Cycle Checkpoints / drug effects*
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Macrophages / ultrastructure
  • Membrane Fluidity / drug effects
  • Mice
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Mycotoxins / toxicity*
  • Polyploidy


  • Cell Cycle Proteins
  • Lactones
  • Mycotoxins
  • alternariol