Electrochemical detection of Oxaliplatin induced DNA damage in G-quadruplex structures


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Arş. Gör. SILA CAN OSMANOĞULLARI

Tez Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Edebiyat Fakültesi, Kimya Bölümü, Türkiye

Tez Danışmanı: Levent Kamil Toppare

Tezin Onay Tarihi: 2022

Tezin Dili: İngilizce

Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu

Desteklendiği Program: YÖK 100/2000 Programı

Özet:

Oxaliplatin is an anticancer agent used in chemotherapy. As a platinum-based chemotherapeutic agent, it is known to induce DNA damage by generating intra- and inter-strand crosslinking mainly at N7 sites of adenine (A) or guanine (G) bases. Thus, a high dosage of Oxaliplatin results in different side effects. In order to understand the molecular mechanisms underlying these side effects and the drug resistance developing against Oxaliplatin, there is a need for rapid qualitative and quantitative determination of Oxaliplatin and the damage caused by it. Electrochemical based methods are one of the sensing platforms that can be preferred due to their sensitivity, simplicity and low cost. In this study, an electroanalytical platform for the detection of DNA damage caused by Oxaliplatin was constructed via using differential pulse voltammetry on gold nanoparticle (Au-NP)-modified graphite electrode. The surface characterization of the prepared electrodes was performed by scanning electron microscopy. The decrease in the intensity of the guanine oxidation signal with increasing Oxaliplatin concentration was taken as an indication of the binding of Oxaliplatin to DNA bases and used in the development of the detection platform with the dynamic range of 1.0 μM to 10.0 μM. The Oxaliplatin induced damage could be detected as low as at 1.0 μM Oxaliplatin concentration under the optimized conditions. These results in here are expected to offer new insights into the investigations of DNA-Oxaliplatin interactions in the future studies.