N2-(1-Carboxyethyl)deoxyguanosine, a Nonenzymatic Glycation Adduct of DNA, Induces Single-Strand Breaks and Increases Mutation Frequencies

Pischetsrieder, Monika; Seidel, Wolfgang; Münch, Gerald; Schinzel, Reinhard

doi:10.1006/bbrc.1999.1528

Cited by 73 publications

(75 citation statements)

References 36 publications

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“…Sucrose irreversibly glycosylates proteins (Dragsted et al 2002). In this context, Pischetsrieder et al (1999) demonstrated that DNA (Mullokandov et al 1994). It is well known that high levels of DNA damage contribute to neurodegeneration (Madabhushi et al 2014, Coppedè andMigliore 2015).…”

Section: Discussionmentioning

confidence: 99%

High consumption of sucrose induces DNA damage in male Wistar rats

Franke

Molz

Mai

et al. 2017

An. Acad. Bras. Ciênc.

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The purpose of this study was to determine the effects of the high consumption of sucrose on the levels of DNA damage in blood, hippocampus and bone marrow of rats. Male Wistar rats were treated for 4 months with sucrose (10% for 60 initial days and 34% for the following 60 days) in drinking water, and then, glycemia and glycated hemoglobin (A1C) were measured. Levels of DNA damage in blood and hippocampus were evaluated by the comet assay. The micronucleus test was used to evaluate chromosomal damages in the bone marrow. The sucrose treatment significantly increased (p<0.01) the serum glucose levels (~20%) and A1C (~60%). The level of primary DNA damage was significantly increased (p<0.05) in hippocampal cells (~60%) but not in peripheral blood leukocytes (p>0.05). Additionally, it was observed a significative increase (p<0.05) in the markers of chromosomal breaks/losses in bone marrow, as indicated by the micronucleus test. This is the first study that evaluated DNA damage induced by high sucrose concentration in the hippocampus and bone marrow of rats. Sucrose-induced DNA damage was observed in both tissues. However, the mechanism of sucrose toxicity on DNA remains unknown.

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Section: Discussionmentioning

confidence: 99%

High consumption of sucrose induces DNA damage in male Wistar rats

Franke

Molz

Mai

et al. 2017

An. Acad. Bras. Ciênc.

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“…DNA adducts arising from MG could induce mutations in E. coli cells and G 3 C and G 3 T transversions in supF gene in mammalian cells (25,26). However, the lesion-containing DNA substrates used in these previous mutagenesis experiments were prepared by the direct treatment of undamaged DNA with dihydroxyacetone or MG (25,26); thus, the identity and homogeneity of the DNA adducts were not carefully assessed.…”

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confidence: 99%

“…However, the lesion-containing DNA substrates used in these previous mutagenesis experiments were prepared by the direct treatment of undamaged DNA with dihydroxyacetone or MG (25,26); thus, the identity and homogeneity of the DNA adducts were not carefully assessed. In light of the previous findings that DinB is capable of bypassing, in an error-free fashion, a number of N 2 -dG lesions (8)(9)(10)(11)(12)(13)(14), we reason that this polymerase may also be involved in the bypass of N 2 -CEdG.…”

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confidence: 99%

Efficient and accurate bypass of N ² -(1-carboxyethyl)-2′-deoxyguanosine by DinB DNA polymerase in vitro and in vivo

Yuan¹,

Cao²,

Jiang

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

135

153

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DinB, a Y-family DNA polymerase, is conserved among all domains of life; however, its endogenous substrates have not been identified. DinB is known to synthesize accurately across a number of N 2 -dG lesions. Methylglyoxal (MG) is a common byproduct of the ubiquitous glycolysis pathway and induces the formation of N 2 -(1-carboxyethyl)-2-deoxyguanosine (N 2 -CEdG) as the major stable DNA adduct. Here, we found that N 2 -CEdG could be detected at a frequency of one lesion per 10 7 nucleosides in WM-266-4 human melanoma cells, and treatment of these cells with MG or glucose led to a dose-responsive increase in N 2 -CEdG formation. We further constructed single-stranded M13 shuttle vectors harboring individual diastereomers of N 2 -CEdG at a specific site and assessed the cytotoxic and mutagenic properties of the lesion in wild-type and bypass polymerase-deficient Escherichia coli cells. Our results revealed that N 2 -CEdG is weakly mutagenic, and DinB (i.e., polymerase IV) is the major DNA polymerase responsible for bypassing the lesion in vivo. Moreover, steady-state kinetic measurements showed that nucleotide insertion, catalyzed by E. coli pol IV or its human counterpart (i.e., polymerase ), opposite the N 2 -CEdG is both accurate and efficient. Taken together, our data support that N 2 -CEdG, a minor-groove DNA adduct arising from MG, is an important endogenous substrate for DinB DNA polymerase.glycolysis ͉ mutagenesis ͉ polymerase ͉ translesion synthesis

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“…The first of these is the receptor-independent modification of the protein structure, leading to the cross-linking of matrix proteins [39] , the decreased catalytic activity of enzymes [40,41] , the occurrence of epitopes with new immunological properties [42] , or the decreased clearance of lipoproteins [43] . DNA damage may be caused via induction of strand breaks, punctual mutations, the occurrence of abasic sites, or depurination [10,44] . Secondly, AGEs interact directly with their specific receptors, of which the receptor for AGEs (RAGE) is of pathogenetic importance.…”

Section: Biological Effects Of Agesmentioning

confidence: 99%

Genomic Damage and Malignancy in End-Stage Renal Failure: Do Advanced Glycation End Products Contribute?

Šebeková

Wagner

Schupp

2006

Kidney Blood Press Res

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In end-stage renal disease (ESRD) there is not only excessive morbidity and mortality due to cardiovascular disease but also an enhanced occurrence of various types of cancer. Both are characterized by oxidative stress and inflammation as two of the central underlying causes of the disease states. In cancer, genomic damage has been demonstrated to be of high pathogenetic relevance. DNA lesions may induce mutations of oncogenes and tumor-suppressor genes which, in the long-run, may lead to malignancies if mutagenicity is not mitigated by repair mechanisms. A high incidence of genomic damage in ESRD patients has been validated by various biomarkers of DNA lesions. We reviewed the mechanisms of DNA damage, focusing in particular on the role of advanced glycation end products (AGEs) which accumulate markedly in renal insufficiency. Considering the in vitro and in vivo findings to date, one has to assume a significant role of AGEs in DNA damage and the potential development of cancer.

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N2-(1-Carboxyethyl)deoxyguanosine, a Nonenzymatic Glycation Adduct of DNA, Induces Single-Strand Breaks and Increases Mutation Frequencies

Cited by 73 publications

References 36 publications

High consumption of sucrose induces DNA damage in male Wistar rats

High consumption of sucrose induces DNA damage in male Wistar rats

Efficient and accurate bypass of N ² -(1-carboxyethyl)-2′-deoxyguanosine by DinB DNA polymerase in vitro and in vivo

Genomic Damage and Malignancy in End-Stage Renal Failure: Do Advanced Glycation End Products Contribute?

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N2-(1-Carboxyethyl)deoxyguanosine, a Nonenzymatic Glycation Adduct of DNA, Induces Single-Strand Breaks and Increases Mutation Frequencies

Cited by 73 publications

References 36 publications

High consumption of sucrose induces DNA damage in male Wistar rats

High consumption of sucrose induces DNA damage in male Wistar rats

Efficient and accurate bypass of N 2 -(1-carboxyethyl)-2′-deoxyguanosine by DinB DNA polymerase in vitro and in vivo

Genomic Damage and Malignancy in End-Stage Renal Failure: Do Advanced Glycation End Products Contribute?

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Efficient and accurate bypass of N ² -(1-carboxyethyl)-2′-deoxyguanosine by DinB DNA polymerase in vitro and in vivo