Detection of benzo[a]pyrene-guanine adducts in single-stranded DNA using the α-hemolysin nanopore

被引：28

作者：

Perera, Rukshan T. ^{[1
]}

Fleming, Aaron M. ^{[1
]}

Johnson, Robert P. ^{[1
]}

Burrows, Cynthia J. ^{[1
]}

White, Henry S. ^{[1
]}

机构：

[1] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA

来源：

NANOTECHNOLOGY | 2015年 / 26卷 / 07期

基金：

美国国家卫生研究院;

关键词：

ion channel; DNA adduct; benzo[a]pyrene; alpha-hemolysin; biomarker; POLYCYCLIC AROMATIC-HYDROCARBONS; DIOL-EPOXIDE; ENVIRONMENTAL EXPOSURE; LIQUID-CHROMATOGRAPHY; CURRENT SIGNATURES; MASS-SPECTROMETRY; CANCER-RISK; DISCRIMINATION; TRANSLOCATION; FLUORESCENCE;

D O I：

10.1088/0957-4484/26/7/074002

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

The carcinogenic precursor benzo[a] pyrene (BP), a polycyclic aromatic hydrocarbon, is released into the environment through the incomplete combustion of hydrocarbons. Metabolism of BP in the human body yields a potent alkylating agent (benzo[a] pyrene diol epoxide, BPDE) that reacts with guanine (G) in DNA to form an adduct implicated in cancer initiation. We report that the alpha-hemolysin (alpha HL) nanopore platform can be used to detect a BPDE adduct to G in synthetic oligodeoxynucleotides. Translocation of a 41-mer poly-2'-deoxycytidine strand with a centrally located BPDE adduct to G through alpha HL in 1 M KCl produces a unique multi-level current signature allowing the adduct to be detected. This readily distinguishable current modulation was observed when the BPDE-adducted DNA strand translocated from either the 5' or 3' directions. This study suggests that BPDE adducts and other large aromatic biomarkers can be detected with aHL, presenting opportunities for the monitoring, quantification, and sequencing of mutagenic compounds from cellular DNA samples.

引用

页数：7

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