Accumulation of DNA damage in the organs of mice deficient in γ- glutamyltranspeptidase

Emilio Rojas, Mahara Valverde, Subbarao V. Kala, Geeta Kala, Michael W. Lieberman

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

We have used a differential alkaline single cell gel electrophoresis assay of DNA ('omet assay' at pH 13 and 12.3) to evaluate DNA damage as a function of age in mice with an inherited defect in gluthathione (GSH) metabolism. The mice are homozygous null for γ-glutamyltranspeptidase (GGT), the enzyme responsible for initiating the catabolism of GSH, and paradoxically have reduced levels of GSH and cysteine in many organs. We found an accumulation of DNA damage in lung, liver and kidney in these mice as a function of age. The largest differences were in assays run at pH 13, suggesting that the accumulation of apurinic/apryrimidinic (AP) sites and oxidative damage of DNA was largely responsible. In contrast, little if any accumulation of these lesions was detected in wild-type mice. Although these findings do not allow a precise analysis of the molecular basis of damage accumulation in GGT-deficient mice, they implicate low GSH and cysteine levels as a cause of accumulative DNA damage in the intact mammal. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)305-316
Number of pages12
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume447
Issue number2
DOIs
StatePublished - Feb 14 2000

Keywords

  • γ-Glumyltranspeptidase
  • Glutathlona single cell gel electrophoresis assay
  • Oxidative stress

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

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