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Updated: Jun 22, 2026

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
04:12

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)

Published on: December 19, 2019

Increased skin carcinogenesis in caspase-activated DNase knockout mice

Bin Yan1, Huili Wang, Donghua Xie

  • 1Department of Radiation Oncology, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA.

Carcinogenesis
|June 23, 2009
PubMed

Insights

Loss of Caspase-activated DNase (CAD) function significantly enhances chemical-induced skin cancer in mice. CAD knockout mice showed increased tumor development and growth in a two-stage carcinogenesis model.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Death Mechanisms

Background:

  • Caspase-activated DNase (CAD), also known as DNA fragmentation factor (DFF), is crucial for DNA fragmentation during apoptosis.
  • CAD/DFF has demonstrated a role in suppressing radiation-induced carcinogenesis by maintaining genomic stability.
  • The specific role of CAD in chemical carcinogenesis remains less understood.

Purpose of the Study:

  • To investigate the role of CAD in chemical carcinogenesis using a two-stage skin carcinogenesis model.
  • To compare tumor development in CAD-null mice versus wild-type littermates.
  • To determine if CAD deficiency influences the initiation and promotion stages of chemical carcinogenesis.

Main Methods:

  • Utilized CAD-null mice and wild-type littermates.
  • Employed a two-stage skin carcinogenesis model involving topical application of dimethylbenz[a]anthracene (DMBA) as an initiator.
  • Used 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoting agent.

Main Results:

  • CAD knockout mice exhibited a 4-fold increase in papillomas per mouse compared to wild-type controls.
  • A 50.8% increase in papilloma incidence was observed in CAD-null mice.
  • Papillomas in CAD-null mice demonstrated accelerated growth and larger tumor sizes.

Conclusions:

  • Loss of CAD function significantly enhances chemical-induced skin tumorigenesis in the DMBA/TPA model.
  • CAD plays a protective role against chemical carcinogenesis, independent of its role in radiation-induced cancer.
  • These findings highlight CAD as a potential target for cancer prevention strategies.

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