SHORT COMMUNICATION: 1, N6-Ethenoadenine and 3, N4-ethenocytosine are excised by separate human DNA glycosylases

Hang, Bo; Chenna, Ahmed; Rao, S.; B, Singer

doi:10.1093/carcin/17.1.155

Cited by 82 publications

(49 citation statements)

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“…The main repair pathway of ⑀dA is via 3-methyladenine DNA glycosylase that excises this exocyclic DNA base. 22,23 However, additional (nucleotide excision) repair pathways may operate in vivo that may liberate this adduct as deoxynucleoside, but this remains to be demonstrated. 1 Intervention group, n ϭ 29; control group, n ϭ 26.-2 Difference between pre-and post-intervention, p Ͻ 0.001.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…As shown in vitro, repair by base excision repair proteins for edA occurs at a faster rate than that for edC, [43][44][45] leading to different adduct levels remaining in tissue DNA. If a nucleotide excision repair pathway eliminates the 2 etheno lesions from tissue DNA with a similar higher preference for edA, one would expect an inverse relation of the repair products in urine as was found indeed in the patients' urine.…”

Section: Random Generation Of Eda In All Liver Cell Nucleimentioning

confidence: 95%

Accumulation of lipid peroxidation‐derived DNA lesions in iron‐overloaded thalassemic mouse livers: Comparison with levels in the lymphocytes of thalassemia patients

Meerang¹,

Nair²,

Sirankapracha³

et al. 2009

Intl Journal of Cancer

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In thalassemia patients, iron overload can stimulate lipid peroxidation (LPO), thereby generating miscoding DNA adducts. Adducted DNA was measured in the lymphocytes of b-Thal/Hb E patients and healthy controls and in the organs of thalassemic mice. edA, edC and M 1 dG residues were quantified by 32 P-postlabeling-TLC/ HPLC. M 1 dG levels in lymphocyte DNA from patients were 4 times as high as in controls, while the increase in edA and edC was not significant. Adducted DNA accumulated in the liver of thalassemic mice having >2.7 mg Fe/g tissue dry weight; DNA adducts and iron were highly correlated. edA was not specifically generated in certain mouse liver cell types as revealed by immunohistochemical staining. We found elevated LPO-induced DNA damage in the liver of thalassemic mouse and in lymphocytes, implicating that massive DNA damage occurs in the liver of thalassemia patients. We conclude that promutagenic LPO-derived DNA lesions are involved in the onset of hepatocellular carcinoma in these patients. ' 2009 UICC Key words: iron overload; lipid peroxidation; thalassemia; etheno-DNA adducts Iron overload, one of the major causes of morbidity and mortality in thalassemia patients, results from multiple, life-long transfusions and enhanced iron absorption as a response to increased erythropoiesis. [1][2][3] Iron overload in these patients is indicated by significantly increased levels of serum ferritin, saturated transferrin (the iron carrier protein) 4 and iron deposition in many organs. 5,6 Administration of the iron chelators, desferrioxamine and deferiprone, is commonly used in therapy. These drugs can cause serious side effects and are expensive. For desferrioxamine, a special infusion equipment is needed and, therefore, not all patients can benefit from iron-chelating therapy. In addition, patients who receive iron chelators still encounter a milder or shorter period of iron overload. As a result of iron overload, high levels of plasma iron in the form of nontransferrin bound iron (NTBI) can be found in both transfusion-dependent and transfusion-independent thalassemia patients. 7 NTBI plays a crucial role in the production of hydroxyl radicals (HO • ) in vivo that occurs through the biological Fenton-type and Haber-Weiss reactions. The resulting hydroxyl radicals can induce oxidative stress and, as a consequence, damage of cellular nucleic acids, proteins, lipids and carbohydrates, which in turn can potentiate tissue damage. 8 Previous studies demonstrated increased oxidative stress in thalassemia patients, including increased antioxidant enzyme activities and decreased nonenzymatic antioxidants. 9-12 Moreover, increase in modified DNA bases such as 8-oxodG, resulting from direct attack of hydroxyl radical to DNA, 13 increase in ortho-and meta-tyrosine, which are products of hydroxyl radical attack on phenylalanine, 14 and increase in lipid peroxidation (LPO) products, such as malondialdehyde (MDA) 10 and F 2 -isoprostane, 15 have been reported.LPO end-products such as 4-hydroxy-2-nonenal (HNE) and 1...

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“…Apparently different cyclic etheno adducts of adenine and cytosine are removed by different glycosylases in human cells [144]. In addition, MPG [130,145,146], but apparently not MAG [91], removes 8-oxoG.…”

Section: Substrate Specificities Of Dna Glycosylases For Alkylated Basesmentioning

confidence: 99%

DNA glycosylases in the base excision repair of DNA

Krokan

Standal

Slupphaug

1997

Biochemical Journal

766

566

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A wide range of cytotoxic and mutagenic DNA bases are removed by different DNA glycosylases, which initiate the base excision repair pathway. DNA glycosylases cleave the Nglycosylic bond between the target base and deoxyribose, thus releasing a free base and leaving an apurinic\apyrimidinic (AP) site. In addition, several DNA glycosylases are bifunctional, since they also display a lyase activity that cleaves the phosphodiester backbone 3h to the AP site generated by the glycosylase activity. Structural data and sequence comparisons have identified common features among many of the DNA glycosylases. Their active sites have a structure that can only bind extrahelical target bases, as observed in the crystal structure of human uracil-DNA glycosylase in a complex with double-stranded DNA. Nucleotide flipping is apparently actively facilitated by the enzyme. With bacteriophage T4 endonuclease V, a pyrimidine-

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SHORT COMMUNICATION: 1, N⁶-Ethenoadenine and ³, N⁴-ethenocytosine are excised by separate human DNA glycosylases

Cited by 82 publications

References 0 publications

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

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

Accumulation of lipid peroxidation‐derived DNA lesions in iron‐overloaded thalassemic mouse livers: Comparison with levels in the lymphocytes of thalassemia patients

DNA glycosylases in the base excision repair of DNA

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SHORT COMMUNICATION: 1, N6-Ethenoadenine and 3, N4-ethenocytosine are excised by separate human DNA glycosylases

Cited by 82 publications

References 0 publications

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

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

Accumulation of lipid peroxidation‐derived DNA lesions in iron‐overloaded thalassemic mouse livers: Comparison with levels in the lymphocytes of thalassemia patients

DNA glycosylases in the base excision repair of DNA

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SHORT COMMUNICATION: 1, N⁶-Ethenoadenine and ³, N⁴-ethenocytosine are excised by separate human DNA glycosylases

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

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