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

Marios G Krokidis1, Maria Louka2, Eleni K Efthimiadou3,4

  • 1Institute of Nanoscience and Nanotechnology, N.C.S.R. "Demokritos", 15310 Agia Paraskevi-Athens, Greece. m.krokidis@inn.demokritos.gr.

Cancers
|April 17, 2019
PubMed

Insights

Cancer progression increases reactive oxygen/nitrogen species (ROS/RNS) damaging DNA and altering erythrocyte membranes. This study reveals combined markers for cancer and aging, offering a holistic view of disease progression.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Increased reactive oxygen/nitrogen species (ROS/RNS) are implicated in cancer development and progression.
  • ROS/RNS cause damage to biomolecules like DNA and lipids within cells.
  • Understanding these molecular changes is crucial for cancer research.

Purpose of the Study:

  • To investigate the parallel remodeling of erythrocyte membrane phospholipids and ROS-induced DNA lesions in a mouse model of cancer.
  • To evaluate the impact of tumor progression and aging on these molecular markers.
  • To explore the potential of combining these markers for a holistic view of cancer and aging.

Main Methods:

  • Utilized a human tumor xenograft mouse model.
  • Analyzed 5',8-cyclo-2'-deoxyadenosine, 5',8-cyclo-2'-deoxyguanosine, and 8-oxo-7,8-dihydro-2'-deoxyadenosine levels in liver and kidney DNA using liquid chromatography tandem mass spectrometry.
  • Assessed fatty acid profiles in erythrocyte membranes.

Main Results:

  • Tumor-bearing mice exhibited elevated ROS-damaged nucleosides in DNA, increasing with age and tumor progression.
  • Significant lipid remodeling in erythrocyte membranes was observed, characterized by polyunsaturated fatty acid (PUFA) consumption and saturated fatty acid (SFA) enrichment.
  • These changes correlated with enhanced oxidative and proliferative processes.

Conclusions:

  • Combined analysis of membrane lipid remodeling and ROS-induced DNA lesions provides an integrated perspective on cancer progression and aging.
  • This holistic approach moves beyond single-compartment biomarker identification.
  • These findings reinforce the interconnectedness of molecular markers in understanding complex biological processes.
Keywords:
fatty acid-based lipidomicsgenotoxic stressmembrane phospholipidsoxidative lesionstumor-bearing mice

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