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Membrane Lipidome Reorganization and Accumulation of Tissue DNA Lesions in Tumor-Bearing Mice: An Exploratory Study

1
Institute of Nanoscience and Nanotechnology, N.C.S.R. “Demokritos”, 15310 Agia Paraskevi-Athens, Greece
2
Lipidomics Laboratory, Lipinutragen srl, Via Piero Gobetti 101, 40129 Bologna, Italy
3
Department of Chemistry, National and Kapodistrian University of Athens, 15784 Zografou, Greece
4
ISOF, Consiglio Nazionale delle Ricerche, Via Piero Gobetti 101, 40129 Bologna, Italy
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(4), 480; https://doi.org/10.3390/cancers11040480
Received: 8 February 2019 / Revised: 1 April 2019 / Accepted: 2 April 2019 / Published: 4 April 2019
(This article belongs to the Special Issue Tumor Xenografts)
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Abstract

Increased rates of reactive oxygen/nitrogen species (ROS/RNS) are involved in almost all cancer types, associated with tumor development and progression, causing damage to biomolecules such as proteins, nucleic acids and membrane lipids, in different biological compartments. We used a human tumor xenograft mouse model to evaluate for the first time in parallel the remodeling of fatty acid moieties in erythrocyte membrane phospholipids and the level of ROS-induced DNA lesions in liver and kidney tissues. Using liquid chromatography tandem mass spectrometry the 5′R and 5′S diastereoisomers of 5′,8-cyclo-2′-deoxyadenosine and 5′,8-cyclo-2′-deoxyguanosine, together with 8-oxo-7,8-dihydro-2′-deoxyadenosine, were determined in mice at young (4- and 5-weeks) and old (17-weeks) ages and compared with control SCID mice without tumor implantation. Tumor-bearing mice showed a higher level of ROS-damaged nucleosides in genomic DNA as the age and tumor progress, compared to controls (1.07–1.53-fold in liver and 1.1–1.4-fold in kidney, respectively). The parallel fatty acid profile of erythrocyte membranes showed a profound lipid remodeling during tumor and age progression consisting of PUFA consumption and SFA enrichment (ca 28% and 58%, respectively, in late stage tumor-bearing mice), markers of enhanced oxidative and proliferative processes, respectively. Membrane lipid remodeling and ROS-induced DNA lesions may be combined to afford an integrated scenario of cancer progression and ageing, reinforcing a holistic vision among molecular markers rather than the biomarker identification in a single compartment. View Full-Text
Keywords: tumor-bearing mice; fatty acid-based lipidomics; membrane phospholipids; oxidative lesions; genotoxic stress tumor-bearing mice; fatty acid-based lipidomics; membrane phospholipids; oxidative lesions; genotoxic stress
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Krokidis, M.G.; Louka, M.; Efthimiadou, E.K.; Zervou, S.-K.; Papadopoulos, K.; Hiskia, A.; Ferreri, C.; Chatgilialoglu, C. Membrane Lipidome Reorganization and Accumulation of Tissue DNA Lesions in Tumor-Bearing Mice: An Exploratory Study. Cancers 2019, 11, 480.

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