Identification of 3,N4-Etheno-5-methyl-2′-deoxycytidine in Human DNA: A New Modified Nucleoside Which May Perturb Genome Methylation

被引：8

作者：

Nair, Jagadeesan ^{[2
]}

Godschalk, Roger W. ^{[1
]}

Nair, Urmila ^{[2
]}

Owen, Robert W. ^{[2
]}

Hull, William E. ^{[2
]}

Bartsch, Helmut ^{[2
]}

机构：

[1] Maastricht Univ, Dept Toxicol, Sch Nutr Toxicol & Metab NUTRIM, Maastricht, Netherlands

[2] German Canc Res Ctr, D-69120 Heidelberg, Germany

来源：

CHEMICAL RESEARCH IN TOXICOLOGY | 2012年 / 25卷 / 01期

关键词：

LIPID-PEROXIDATION; HUMAN-DISEASE; ADDUCT TYPES; LIVER DNA; REPAIR; HYPOMETHYLATION; CANCER; DAMAGE; N-4-ETHENOCYTOSINE; METHYLTRANSFERASE;

D O I：

10.1021/tx200392a

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Methylation of cytidine at dCpdG sequences regulates gene expression and is altered in many chronic inflammatory diseases. Inflammation generates lipid peroxidation (LPO) products which can react with deoxycytidine, deoxyadenosine, and deoxyguanosine in DNA to form pro-mutagenic exocyclic etheno-nucleoside residues. Since 5-methyl-2'-deoxycytidine (5mdC) residues exhibit increased nucleophilicity at N3, they should be even better targets for LPO products. We synthesized and characterized 3,N-4-etheno-5-methyl-2'-deoxycytidine-3'-phosphate and showed that LPO products can indeed form the corresponding etheno-5mdC (epsilon 5mdC) lesion in DNA in vitro. Our newly developed P-32-postlabeling method was subsequently used to detect epsilon 5mdC lesions in DNA from human white blood cells, lung, and liver at concentrations 4-10 times higher than that observed for etheno adducts on nonmethylated cytidine. Our new detection method can now be used to explore the hypothesis that this DNA lesion perturbs the DNA methylation status.

引用

页码：162 / 169

页数：8

共 3 条

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BIOMARKERS, 2006, 11 (04) : 329 - 340
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YOSHINO, H
MATSUNAGA, H
KANEKO, H
YOSHITAKE, A
NAKATSUKA, I
YAMADA, H
XENOBIOTICA, 1993, 23 (06) : 609 - 619

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