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Spontaneous mutagenesis in Csb(m/m)Ogg1⁻(/)⁻ mice is attenuated by dietary resveratrol

Markus Fusser1, Gaute J Nesse, Andriy Khobta

  • 1Institute of Pharmacy and Biochemistry, University of Mainz, Germany.

Carcinogenesis
|November 11, 2010
PubMed

Insights

Resveratrol, a plant compound, significantly reduces oxidative DNA damage and spontaneous mutations in mice with impaired DNA repair. This protection is linked to enhanced antioxidant defenses, suggesting a potential strategy to lower cancer risk from DNA damage.

Area of Science:

  • Biochemistry
  • Genetics
  • Molecular Biology

Background:

  • Oxidative DNA damage, including 7,8-dihydro-8-oxoguanine (8-oxoG), occurs naturally in cells.
  • Defective repair of 8-oxoG in Csb(m/m)Ogg1⁻(/)⁻ mice leads to increased DNA lesions and mutations, promoting liver tumorigenesis.

Purpose of the Study:

  • To investigate the effect of resveratrol on endogenous oxidative DNA base damage and spontaneous mutation frequencies in Csb(m/m)Ogg1⁻(/)⁻ mice.
  • To elucidate the protective mechanisms of resveratrol against oxidative DNA damage.

Main Methods:

  • Administration of resveratrol via gavage or diet to Csb(m/m)Ogg1⁻(/)⁻ and wild-type mice.
  • Quantification of oxidative DNA base damage and spontaneous mutation frequencies (lacI gene).
  • Assessment of hepatocyte susceptibility to H₂O₂-induced damage and cell death.
  • Measurement of antioxidant enzyme mRNA levels (SOD1, SOD2, heme oxygenase-1, glutathione peroxidase).

Main Results:

  • Resveratrol treatment reduced endogenous oxidative DNA base damage by 20-30% in Csb(m/m)Ogg1⁻(/)⁻ mice and showed a smaller effect in wild-type animals.
  • Spontaneous mutation frequencies in the lacI gene were similarly reduced by resveratrol.
  • Hepatocytes from resveratrol-treated mice exhibited increased resistance to H₂O₂.
  • Upregulation of antioxidant enzyme mRNA levels (SOD1, SOD2, heme oxygenase-1, glutathione peroxidase) was observed.
  • Mutations linked to 8-oxoG were more effectively suppressed than those from spontaneous deamination.

Conclusions:

  • Resveratrol effectively reduces endogenous oxidative DNA damage and spontaneous somatic mutation rates.
  • The protective effect is mediated by the induction of the antioxidant defense system.
  • These findings suggest resveratrol as a potential agent to mitigate risks associated with oxidative DNA damage.

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