Related Experiment Video

Updated: Jun 25, 2026

Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel
08:29

Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel

Published on: May 14, 2018

Modulation of key regulators of mitosis linked to chromosomal instability is an early event in ochratoxin A

Melanie Adler1, Katja Müller, Eva Rached

  • 1Department of Toxicology, University of Würzburg, Versbacher Strasse 9, 97078 Würzburg, Germany.

Carcinogenesis
|February 25, 2009
PubMed

Insights

Ochratoxin A (OTA) disrupts mitosis, causing cell death and proliferation. This disruption leads to gene deregulation linked to cancer, suggesting aberrant mitosis is key to OTA carcinogenicity.

Area of Science:

  • Toxicology
  • Molecular Biology
  • Carcinogenesis

Background:

  • Ochratoxin A (OTA) is a known kidney carcinogen.
  • The precise mechanism of OTA-induced carcinogenicity remains unclear.
  • Early kidney alterations include cell death, proliferation, and karyomegaly, suggesting mitotic disruption.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying OTA carcinogenicity.
  • To examine the impact of OTA on cell cycle control and mitosis gene expression in rat kidneys.

Main Methods:

  • Targeted quantitative real-time polymerase chain reaction (PCR) arrays were used.
  • Gene expression analysis was performed on kidneys of male F344 rats treated with varying OTA doses (0-210 microg/kg) for up to 90 days.
  • Immunohistochemistry confirmed protein upregulation and mitotic activity.

Main Results:

  • OTA treatment upregulated key mitotic regulators: Polo-like kinase 1, Aurora B, cyclin-dependent kinase 1 (Cdk1Cdc2), cyclins, cyclin-dependent kinase inhibitors, topoisomerase II, and survivin.
  • Immunohistochemistry confirmed Cdk1, p21(WAF1/CIP1), topoisomerase II, and survivin upregulation in proximal tubule cells.
  • Increased histone H3 phosphorylation indicated Aurora B activity.

Conclusions:

  • Aberrant mitosis, including blocked or asymmetric cell division, is a critical factor in OTA carcinogenicity.
  • Deregulation of genes involved in mitosis is linked to chromosomal instability and malignant transformation.
  • OTA's disruption of cell division processes contributes to kidney cancer development.

More Related Videos

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer09:40

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
Molecular Factors Affecting Cell Division01:27

Molecular Factors Affecting Cell Division

Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.