TY - JOUR
T1 - Accumulation of DNA damage in the organs of mice deficient in γ- glutamyltranspeptidase
AU - Rojas, Emilio
AU - Valverde, Mahara
AU - Kala, Subbarao V.
AU - Kala, Geeta
AU - Lieberman, Michael W.
N1 - Funding Information:
Supported by NIH Grant ES 07827 (MWL).
PY - 2000/2/14
Y1 - 2000/2/14
N2 - 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.
AB - 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.
KW - γ-Glumyltranspeptidase
KW - Glutathlona single cell gel electrophoresis assay
KW - Oxidative stress
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U2 - 10.1016/S0027-5107(99)00191-8
DO - 10.1016/S0027-5107(99)00191-8
M3 - Article
C2 - 10751614
AN - SCOPUS:0034646078
SN - 0027-5107
VL - 447
SP - 305
EP - 316
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 2
ER -