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Mechanisms of action of oxidant carcinogens

P A Cerutti1

  • 1Department of Carcinogenesis, Swiss Institute for Experimental Cancer Research, Epalinges/Lausanne.

Cancer Detection and Prevention
|January 1, 1989
PubMed

Insights

Oxidants contribute to cancer by damaging DNA and altering gene expression. Poly ADP-ribosylation, an epigenetic response to DNA breaks, modulates gene transcription, including key cancer-related genes like c-fos.

Area of Science:

  • Molecular biology
  • Carcinogenesis
  • Oxidative stress

Background:

  • Oxidants play a dual role in carcinogenesis, causing genetic damage and activating cellular pathways.
  • Oxidant-induced pathways can mimic those activated by growth factors and hormones, affecting gene expression, growth, and differentiation.

Purpose of the Study:

  • To investigate the role of oxidants in modulating gene expression during carcinogenesis.
  • To explore the significance of poly ADP-ribosylation in response to oxidant-induced DNA damage.

Main Methods:

  • Examined oxidant effects on cellular pathways, including protein phosphorylation and protooncogene transcription (c-fos, c-myc).
  • Investigated poly ADP-ribosylation of chromosomal proteins (histones and nonhistones) in response to oxidants.
  • Assessed the impact of inhibiting poly ADP-ribosylation on oxidant-induced c-fos transcription.

Main Results:

  • Oxidants stimulate pathways like S6 ribosomal protein phosphorylation and protein kinase C activation.
  • Oxidants increase transcription of protooncogenes c-fos and c-myc.
  • Poly ADP-ribosylation of chromosomal proteins, including the fos oncoprotein, occurs in response to oxidants and is linked to c-fos transcription.

Conclusions:

  • Oxidants influence carcinogenesis through genetic damage and altered gene expression.
  • Poly ADP-ribosylation is a critical epigenetic mechanism in response to oxidant-induced DNA damage.
  • The poly ADP-ribosylation of proteins like fos may regulate gene expression under oxidative stress.

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