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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 möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
Zeitschrift Free Radical Biology and Medicine
Quellenangaben Band: 32, Heft: , Seiten: 663-673 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)
Institute of Clinical Molecular Biology and Tumor Genetics (K.MOLBI)