Etheno adducts in spleen DNA of SJL mice stimulated to overproduce nitric oxide

Nair, Jagadeesan; Gal, Aharon; Tamir, Snait; Tannenbaum, Steven R.; Wogan, Gerald N.; Bartsch, Helmut

doi:10.1093/carcin/19.12.2081

Cited by 79 publications

(41 citation statements)

References 29 publications

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“…This model is supported by the lack of a correlation between M 1 dG and lipid peroxidation-derived etheno adducts and by the positive correlation between M 1 dG and 8-oxo-dG, a DNA oxidation product, in human pancreas (7). Similar results have been obtained in the SJL/RcsX mouse model of nitric oxide overproduction in which it was observed that etheno-dA adducts increase severalfold in inflamed spleens (52), whereas M 1 dG levels were unchanged from values obtained in non-inflamed mice. 2 The second notable observation was the apparent protective effect of PUFA with regard to M 1 dG formation.…”

Section: Discussionsupporting

confidence: 87%

Chemical and Biological Evidence for Base Propenals as the Major Sourceof the Endogenous M1dG Adduct in CellularDNA

Zhou

Taghizadeh

Dedon

2005

Journal of Biological Chemistry

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The endogenous DNA adduct, M 1 dG, has been shown to arise in vitro in reactions of dG with malondialdehyde (MDA), a product of both lipid peroxidation and 4-oxidation of deoxyribose in DNA, and with base propenals also derived from deoxyribose 4-oxidation. We now report the results of cellular studies consistent with base propenals, and not MDA, as the major source of M 1 dG under biological conditions. As a foundation for cellular studies, M 1 dG, base propenals, and MDA were quantified in purified DNA treated with oxidizing agents known to produce deoxyribose 4-oxidation. The results revealed a consistent pattern; Fe 2؉ -EDTA and ␥-radiation generated MDA but not base propenals or M 1 dG, whereas bleomycin and peroxynitrite (ONOO ؊ ) both produced M 1 dG as well as base propenals with no detectable MDA. These observations were then assessed in Escherichia coli with controlled membrane levels of polyunsaturated fatty acids (PUFA). ONOO ؊ treatment (2 mM) of cells containing no PUFA (defined medium with 18:0/stearic acid) produced 6.5 M 1 dG/10 7 deoxynucleotides and no detectable lipid peroxidation products, including MDA, as compared with 3.8 M 1 dG/ 10 7 deoxynucleotides and 0.07 g/ml lipid peroxidation products with control cells grown in a mixture of fatty acids (0.5% PUFA) mimicking Luria-Bertani medium. In cells grown with linoleic acid (18:2), the level of PUFA rose to 54% and the level of MDA rose to 0.14 g/ml, whereas M 1 dG fell to 1.4/10 7 deoxynucleotides. Parallel studies with ␥-radiation revealed levels of MDA similar to those produced by ONOO ؊ but no detectable M 1 dG. These results are consistent with base propenals as the major source of M 1 dG in this model cell system.

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Section: Discussionsupporting

confidence: 87%

Chemical and Biological Evidence for Base Propenals as the Major Sourceof the Endogenous M1dG Adduct in CellularDNA

Zhou

Taghizadeh

Dedon

2005

Journal of Biological Chemistry

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“…Increased ⑀-DNA adducts were shown to occur in the spleen DNA of SJL-mice that overexpressed iNOS. 6 In our longitudinal observation, only the salt excretion was significantly decreased by the intervention (Table II) and the ⑀dA excretion was also decreased (trend only). The reduction of ⑀dA might be caused by the decreased salt intake.…”

Section: Etheno Adducts In Urinementioning

confidence: 55%

“…5 Moreover, SJL mice injected with RcsX cells, which overexpress inducible nitric oxide synthase (iNOS) exhibited 50-fold increase in nitric oxide (NO) production and 6 times higher ⑀-adduct levels in the spleen DNA compared with the controls. 6 This observation has suggested that the ⑀-adduct formation is increased by chronic inflammatory processes and neoplasias and thus could be involved in Helicobacter pylori infection, chronic gastritis and gastric cancer. 6 Recently a sensitive detection method has been established to measure 1,N 6 -ethenodeoxyadenosine (⑀dA) in small amounts of human urine.…”

mentioning

confidence: 99%

“…6 This observation has suggested that the ⑀-adduct formation is increased by chronic inflammatory processes and neoplasias and thus could be involved in Helicobacter pylori infection, chronic gastritis and gastric cancer. 6 Recently a sensitive detection method has been established to measure 1,N 6 -ethenodeoxyadenosine (⑀dA) in small amounts of human urine. 7 ⑀dA in urine could arise either from its formation in the nucleoside pool or as a consequence of its repair of damaged DNA bases in cellular DNA.…”

mentioning

confidence: 99%

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Urinary level of 1,N⁶ ‐ethenodeoxyadenosine, a marker of oxidative stress, is associated with salt excretion and ω6‐polyunsaturated fatty acid intake in postmenopausal Japanese women

Hanaoka

Nair

Takahashi

et al. 2002

Intl Journal of Cancer

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Excretion of 1,N 6 -ethenodeoxyadenosine (⑀dA), a marker for lipid peroxidation (LPO)-derived DNA damage was analyzed in urine of nonsmoking postmenopausal women participating in a dietary intervention trial in Northern Japan. Hereby the efficacy of dietary consultation in reducing salt and increasing vitamin C and carotenes during 1 year was estimated. Thirty postmenopausal women, 60 -69 years of age, from the intervention group and 30 age-matched women from the control group were randomly selected. The subjects completed a self-administered diet history questionnaire and in the pre-and post-intervention period 48 hr urine and fasting blood samples were collected. ⑀dA in urine was analyzed by an immuno-precipitation-high performance liquid chromatography-fluorescence detection method. ⑀dA excretion (/48 hr) in the 59 postmenopausal Japanese women with complete urine collection ranged from 12-226 pmol at the pre-intervention. At the pre-intervention, ⑀dA excretion was positively associated with urinary salt excretion (R ‫؍‬ 0.33, p ‫؍‬ 0.01) and -6 polyunsaturated fatty acid intake (%energy value, R ‫؍‬ 0.28, p ‫؍‬ 0.03) in the 59 women. The average ⑀dA excretion in the intervention group was 61 pmol at pre-intervention and 44 pmol at post-intervention (p ‫؍‬ 0.14). In the control group, it was 58 pmol at pre-intervention and 75 pmol at post-intervention (p ‫؍‬ 0.24). During the intervention period, 18/29 (62%) of the subjects in the intervention group exhibited the decreased excretion and 10/26 (38%) in the control group (p ‫؍‬ 0.08). Results from this pilot study suggest urinary ⑀dA as a potential biomarker of DNA damage possibly derived from salt-induced inflammation and LPO; further exploration of ⑀dA in human biomonitoring studies is warranted. © 2002 Wiley-Liss, Inc. Key words : etheno DNA adducts; urinary excretion; salt; polyunsaturated fatty acids; diet; cancer Oxidative stress is caused by a net imbalance of pro-oxidants to anti-oxidants in the cell and is implicated in carcinogenesis. 1 Dietary components are one of the major sources of exogenous pro-oxidants and anti-oxidants for the body. Modulation of antioxidant intake could influence the pro-/anti-oxidant balance resulting in reduced cellular oxidative stress. Validation and application of biomarkers of oxidative stress in dietary intervention studies is essential in evaluating effective prevention strategies against oxyradicals and associated malignancies.Etheno ⑀-DNA adducts are formed as stable DNA base adducts from reactive aldehydes such trans-4-hydroxy-2-nonenal generated during the oxidative stress or lipid peroxidation (LPO). 2 It has been demonstrated that ⑀-DNA adducts were present in asymptomatic liver of humans, suggesting that these lesions could arise from endogenously formed LPO products. 3 An in vitro study showed that arachidonic acid in the presence of LPO inducing compounds led to the generation of ⑀-DNA-base adducts. 4 Our previous study also revealed that ⑀-adducts were increased in WBC-DNA of the females as a result of...

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“…35 The method yields results in accord with reliable published analyses of individual lesions in animal tissues. 36,37 …”

Section: Introductionmentioning

confidence: 99%

Quantification of DNA damage products resulting from deamination, oxidation and reaction with products of lipid peroxidation by liquid chromatography isotope dilution tandem mass spectrometry

et al. 2008

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The analysis of damage products as biomarkers of inflammation has been hampered by a poor understanding of the chemical biology of inflammation, the lack of sensitive analytical methods, and a focus on single chemicals as surrogates for inflammation. To overcome these problems, we developed a general and sensitive liquid chromatographic tandem mass spectrometry (LC/MS-MS) method to quantify, in a single DNA sample, the nucleoside forms of seven DNA lesions reflecting the range of chemistries associated with inflammation: 2′-deoxyuridine, 2′-deoxyxanthosine, and 2′-deoxyinosine from nitrosative deamination; 8-oxo-2′-deoxyguanosine from oxidation; and 1,N 2 -etheno-2′-deoxyguanosine, 1,N 6 -etheno-2′-deoxyadenosine, and 3,N 4 -etheno-2′-deoxycytidine arising from reaction of DNA with lipid peroxidation products. Using DNA purified from cells or tissues under conditions that minimize artifacts, individual nucleosides are purified by HPLC and quantified by isotope-dilution, electrospray ionization LC/MS-MS. The method can be applied to other DNA damage products and requires 4-6 days to complete depending upon the number of samples. Search terms

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Etheno adducts in spleen DNA of SJL mice stimulated to overproduce nitric oxide

Cited by 79 publications

References 29 publications

Chemical and Biological Evidence for Base Propenals as the Major Sourceof the Endogenous M1dG Adduct in CellularDNA

Chemical and Biological Evidence for Base Propenals as the Major Sourceof the Endogenous M1dG Adduct in CellularDNA

Urinary level of 1,N⁶ ‐ethenodeoxyadenosine, a marker of oxidative stress, is associated with salt excretion and ω6‐polyunsaturated fatty acid intake in postmenopausal Japanese women

Quantification of DNA damage products resulting from deamination, oxidation and reaction with products of lipid peroxidation by liquid chromatography isotope dilution tandem mass spectrometry

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Etheno adducts in spleen DNA of SJL mice stimulated to overproduce nitric oxide

Cited by 79 publications

References 29 publications

Chemical and Biological Evidence for Base Propenals as the Major Sourceof the Endogenous M1dG Adduct in CellularDNA

Chemical and Biological Evidence for Base Propenals as the Major Sourceof the Endogenous M1dG Adduct in CellularDNA

Urinary level of 1,N6 ‐ethenodeoxyadenosine, a marker of oxidative stress, is associated with salt excretion and ω6‐polyunsaturated fatty acid intake in postmenopausal Japanese women

Quantification of DNA damage products resulting from deamination, oxidation and reaction with products of lipid peroxidation by liquid chromatography isotope dilution tandem mass spectrometry

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Urinary level of 1,N⁶ ‐ethenodeoxyadenosine, a marker of oxidative stress, is associated with salt excretion and ω6‐polyunsaturated fatty acid intake in postmenopausal Japanese women