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Felix, K.* ; Rockwood, L.D.* ; Pretsch, W. ; Nair, J.* ; Bartsch, H.* ; Bornkamm, G.W. ; Janz, S.*

Moderate G6PD deficiency increases mutation rates in the brain of mice.

Free Radical Biol. Med. 32, 663-673 (2002)
Open Access Green as soon as Postprint is submitted to ZB.
Mice that harbored the x-ray-induced low efficiency allele of the major X-linked isozyme of glucose-6-phospate dehydrogenase (G6PD), Gpdx(a-m2Neu), and, in addition, harbored the transgenic shuttle vector for the determination of mutagenesis in vivo, pUR288, were employed to further our understanding of the interdependence of general metabolism, oxidative stress control, and somatic mutagenesis. The Gpdx(a-m2Neu) mutation conferred moderate G6PD deficiency in hemizygous males (Gpdx(a-m2Neu/y)) displaying residual enzyme activities of 27% in red blood cells and 13% in brain (compared to wild-type controls, Gpdx(a/y) males). In spite of this mild phenotype, the brains of G6PD-deficient males exhibited a significant distortion of redox control (similar to3-fold decrease in the ratio of reduced glutathione to oxidized glutathione), a considerable accumulation of promutagenic etheno DNA adducts (similar to13-fold increase in ethenodeoxyadenosine and similar to5-fold increase in ethenodeoxycytidine), and a substantial elevation of somatic mutation rates (similar to3-fold increase in mutant frequencies in lacZ, the target and reporter gene of mutagenesis in the shuttle vector, pUR288). The mutation pattern in the brain was dominated by illegitimate genetic recombinations, a presumed hallmark of oxidative mutagenesis. These findings suggested a critical function for G6PD in limiting oxidative mutagenesis in the mouse brain.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Glucose-6-phosphate dehydrogenase Endogenous oxidative stress In vivo mutagenicity reporter gene lacZ Etheno DNA adducts Free radicals
ISSN (print) / ISBN 0891-5849
e-ISSN 1873-4596
Journal Free Radical Biology and Medicine
Quellenangaben Volume: 32, Issue: , Pages: 663-673 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
Institute of Clinical Molecular Biology and Tumor Genetics (K.MOLBI)