Electrochemical detection of 7-methylguanosine and DNA-methylation

DNA damage has been associated with cancer. Alkylating agents interact with DNA to yield a variety of products, such as 7-methylguanosine (7-mGuo), a predominant adduct, 5-methylcytosine, 3-methyladenosine and o -6-methylguanosine. This work revealed, for the first time, the oxidation mechanism of 7...

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Veröffentlicht in:Analytical methods 2018-01, Vol.1 (37), p.4525-4534
Hauptverfasser: do Nascimento, Raphael F, Nascimento, José A. M, Montenegro, João G. S, Nascimento, Valberes B, Oliveira, Severino Carlos B
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Sprache:eng
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Zusammenfassung:DNA damage has been associated with cancer. Alkylating agents interact with DNA to yield a variety of products, such as 7-methylguanosine (7-mGuo), a predominant adduct, 5-methylcytosine, 3-methyladenosine and o -6-methylguanosine. This work revealed, for the first time, the oxidation mechanism of 7-mGuo on a glassy carbon electrode (GCE) using cyclic and differential pulse voltammetry, as well as impedance spectroscopy. 7-mGuo is irreversibly oxidized in a pH dependent single step reaction, predominantly under diffusion control. The anodic behaviour of 7-mGuo was compared with the anodic behaviour of other guanine derivatives. An electroanalytical method was proposed for the determination of 7-mGuo using a GCE by differential pulse voltammetry at physiological pH, with a limit of detection of 3.26 μmol L −1 and a limit of quantification of 10.88 μmol L −1 . The electrochemical detection of 7-mGuo was also investigated in the presence of the potential interferents guanine, guanosine and 7-methylguanine (7-mGua). The study demonstrated that the anodic peak of 7-mGuo did not suffer from any interference from these species, since its oxidation happens at a very distinct potential. A differential pulse voltammetry study of 7-mGua and 7-mGuo in the presence of double-helix DNA (dsDNA) or DNA bases was carried out aiming to investigate the possibility of using a DNA-electrochemical biosensor for detection of DNA methylation. The electrochemical data revealed that the DNA methylation damage can be detected by a distinct signal and quantified using a DNA biosensor. DNA methylation damage can be detected using a DNA-electrochemical biosensor.
ISSN:1759-9660
1759-9679
DOI:10.1039/c8ay01667d