1. Purine 5′,8-cyclo-2′-deoxynucleoside lesions: formation by radical stress and repair in human breast epithelial cancer cells
- Author
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Chryssostomos Chatgilialoglu, Michael A. Terzidis, Dimitris Kletsas, Anastasia Hiskia, Kyriakos Papadopoulos, George Kordas, Sevasti-Kiriaki Zervou, Eleni K. Efthimiadou, and Marios G. Krokidis
- Subjects
0301 basic medicine ,DNA damage ,DNA repair ,Breast Neoplasms ,medicine.disease_cause ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Free radicals ,breast cancer ,isotope dilution LC-MS/MS ,0302 clinical medicine ,Deoxyadenosine ,medicine ,Humans ,Mammary Glands, Human ,Deoxyadenosines ,Cancer ,Epithelial Cells ,General Medicine ,Base excision repair ,DNA repair protein XRCC4 ,medicine.disease ,Molecular biology ,Oxidative Stress ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,MCF-7 Cells ,Female ,Reactive Oxygen Species ,Carcinogenesis ,DNA Damage ,Nucleotide excision repair - Abstract
5',8-Cyclo-2'-deoxyadenosine (cdA) and 5',8-cyclo-2'-deoxyguanosine (cdG) in their two diastereomeric forms, 5'S and 5'R, are tandem lesions produced by the attack of hydroxyl radicals to the purine moieties of DNA. Their formation has been found to challenge the cells' repair machinery, initiating the nucleotide excision repair (NER) for restoring the genome integrity. The involvement of oxidatively induced DNA damage in carcinogenesis and the reduced capacity of some cancer cell lines to repair oxidised DNA base lesions, intrigued us to investigate the implication of these lesions in breast cancer, the most frequently occurring cancer in women. Using liquid chromatography tandem mass spectrometry (LC-MS/MS), we measured the levels of diastereomeric cdA's and cdG's in estrogen receptor-alpha positive (ER-alpha) MCF-7 and triple negative MDA-MB-231 breast cancer cell lines before and after exposure to two different conditions: ionising radiations and hydrogen peroxide, followed by an interval period to allow DNA repair. An increase at the measured levels of all four lesions, i.e. 5'S-cdA, 5'R-cdA, 5'S-cdG and 5'R-cdG, was observed either after gamma-irradiation (5Gy dose) or hydrogen peroxide treatment (300muM) compared to the untreated cells (control), independently from the length of the interval period for repair. For comparison reasons, we also measured the levels of 8-oxo-2'-deoxyadenosine (8-oxo-dA), a well-known oxidatively induced DNA damage lesion and base excision repair (BER) substrate. The collected data indicate that MCF-7 and MDA-MB-231 breast cancer cells are highly susceptible to radiation-induced DNA damage, being mainly defective in the repair of these lesions.
- Published
- 2017
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