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Survival of aneuploid, micronucleated and/or polyploid cells: crosstalk between ploidy control and apoptosis

Ilse Decordier1, Enrico Cundari, Micheline Kirsch-Volders

  • 1Vrije Universiteit Brussel, Laboratorium voor Cellulaire Genetica, Pleinlaan 2, 1050 Brussels, Belgium. idecordi@vub.ac.be

Mutation Research
|February 5, 2008
PubMed

Insights

Microtubule inhibitor nocodazole can cause polyploidy or aneuploidy. Micronucleated cells, arising from chromosome loss, are eliminated by apoptosis, which involves caspase-3.

Area of Science:

  • Cell Biology
  • Genetics
  • Toxicology

Background:

  • Microtubule inhibitors disrupt cell division at M-phase.
  • Cellular escape from mitotic arrest can lead to aneuploidy, polyploidy, and micronuclei.
  • These chromosomal abnormalities are linked to adverse health outcomes, including cancer and developmental defects.

Purpose of the Study:

  • To review laboratory data on the relationship between nocodazole-induced aneuploidy, polyploidy, micronuclei, and apoptosis in human cells.
  • To investigate the role of p53 status in the fate of polyploid cells.
  • To elucidate the specific apoptotic pathways and caspases involved in nocodazole treatment.

Main Methods:

  • In vitro exposure of human cells to the microtubule inhibitor nocodazole at varying concentrations.
  • Analysis of cell cycle progression, ploidy status (aneuploidy, polyploidy), and micronuclei formation.
  • Assessment of apoptosis induction and the involvement of key caspases (caspase-8, -9, -3).

Main Results:

  • High-dose nocodazole induces polyploidy via mitotic slippage, with cell fate dependent on p53 status; polyploidy is not a strong apoptotic signal.
  • Low-dose nocodazole causes microtubule damage, leading to chromosome loss and non-disjunction.
  • Micronucleated cells, resulting from chromosome loss, can be eliminated by apoptosis.
  • Nocodazole-induced apoptosis involves apical caspases-8 and -9, and effector caspase-3.
  • Caspase-3 plays a dual role in apoptosis and micronuclei formation.

Conclusions:

  • Nocodazole's effects on human cells depend on dose, leading to polyploidy or aneuploidy.
  • Apoptosis effectively eliminates micronucleated cells, suggesting a protective mechanism against aneuploidy.
  • Caspase-3 is a key mediator in nocodazole-induced apoptosis and also contributes to micronuclei formation.

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