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Related Experiment Videos

Pathophysiological mechanisms of active oxygen.

P Cerutti1, R Larsson, G Krupitza

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

Mutation Research
|September 1, 1989
PubMed
Summary

Oxidants can promote tumor growth by stimulating cell proliferation. Promotable cells possess higher antioxidant enzyme levels, protecting them from oxidant-induced damage and promoting growth.

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Area of Science:

  • Cell Biology
  • Toxicology
  • Oncology

Background:

  • Oxidants can induce pathophysiological effects in mammalian cells, potentially acting as natural tumor promoters.
  • Understanding the mechanisms of oxidant-induced tumor promotion is crucial for cancer research.

Purpose of the Study:

  • To investigate the mechanism of action of oxidant promoters using a model of promotable and non-promotable mouse epidermal cells.
  • To elucidate the role of antioxidant defenses in cellular responses to oxidants.

Main Methods:

  • Utilized JB6 mouse epidermal cell clones (promotable clone 41 and non-promotable clone 30) exposed to active oxygen (AO) generated by xanthine/xanthine-oxidase.
  • Assessed cell growth, DNA damage, poly ADP-ribosylation, proto-oncogene expression (c-fos, c-myc), and antioxidant enzyme activities (catalase, Cu,Zn-superoxide dismutase, glutathione-peroxidase).

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Main Results:

  • Active oxygen (AO) stimulated growth in promotable clone 41 but was cytostatic to non-promotable clone 30.
  • Non-promotable cells exhibited greater DNA-strand breaks and poly ADP-ribosylation upon AO exposure.
  • Both clones showed AO-induced expression of c-fos and c-myc proto-oncogenes.
  • Promotable clone 41 displayed 2-3 fold higher constitutive levels of catalase (CAT) and Cu,Zn-superoxide dismutase (SOD) compared to non-promotable clone 30.

Conclusions:

  • Promotable cells possess a superior antioxidant defense system, particularly higher levels of CAT and SOD.
  • This enhanced antioxidant capacity protects promotable cells from excessive cytostatic effects of oxidants, allowing for growth stimulation.
  • Differences in antioxidant defenses explain the differential cellular responses to oxidant tumor promoters.