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Topical application of ochratoxin A causes DNA damage and tumor initiation in mouse skin

Rahul Kumar1, Kausar M Ansari, Bhushan P Chaudhari

  • 1Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, Uttar Pradesh, India.

Plos One
|October 17, 2012
PubMed

Insights

Environmental toxin ochratoxin A (OTA) causes DNA damage and skin tumors in mice. This mycotoxin exposure may increase skin cancer risk, particularly for agricultural workers. Further research is needed.

Area of Science:

  • Toxicology
  • Dermatology
  • Carcinogenesis

Background:

  • Skin cancer is a prevalent global health concern, with millions diagnosed annually.
  • Environmental factors, including mycotoxins, are implicated as potential etiological agents in skin cancer development.
  • Occupational exposure to mycotoxins like ochratoxin A (OTA) is possible in agricultural settings.

Purpose of the Study:

  • To evaluate the DNA damaging potential of ochratoxin A (OTA) via topical application.
  • To assess the dermal carcinogenicity of OTA in a mouse model.
  • To elucidate the molecular mechanisms underlying OTA-induced skin damage and tumor initiation.

Main Methods:

  • Single topical application of OTA (20–80 µg/mouse) to mice.
  • Analysis of DNA damage markers (e.g., γ-H2AX) and oxidative stress indicators.
  • Investigation of molecular pathways including Nrf2, MAPKs, cell cycle regulation, apoptosis, and specific protein expressions.
  • Two-stage mouse skin tumorigenesis protocol involving OTA and a tumor promoter (12-O-tetradecanoylphorbol-13-acetate).

Main Results:

  • OTA induced significant DNA damage and elevated γ-H2AX levels in mouse skin.
  • Dose- and time-dependent alterations in oxidative stress markers and suppression of Nrf2 translocation were observed.
  • OTA triggered reactive oxygen species generation, MAPK activation, cell cycle arrest, apoptosis, and modulated key proteins involved in cell death and survival.
  • OTA demonstrated skin tumor-initiating properties in the mouse model.

Conclusions:

  • Ochratoxin A possesses DNA damaging potential and dermal carcinogenicity.
  • Oxidative stress, MAPKs signaling, and DNA damage are likely mechanisms mediating OTA's tumor-initiating effects.
  • Findings highlight OTA as a potential environmental risk factor for skin cancer, especially in occupational contexts.

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