Effects of Aging and Disease Conditions in Brain of Tumor-Bearing Mice: Evaluation of Purine DNA Damages and Fatty Acid Pool Changes

Abstract

The consequences of aging and disease conditions in tissues involve reactive oxygen species (ROS) and related molecular alterations of different cellular compartments. We compared a murine model of immunodeficient (SCID) xenografted young (4 weeks old) and old (17 weeks old) mice with corresponding controls without tumor implantation and carried out a compositional evaluation of brain tissue for changes in parallel DNA and lipids compartments. DNA damage was measured by four purine 5′,8-cyclo-2′-deoxynucleosides, 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG), and 8-oxo-7,8-dihydro-2′-deoxyadenosine (8-oxo-dA). In brain lipids, the twelve most representative fatty acid levels, which were mostly obtained from the transformation of glycerophospholipids, were followed up during the aging and disease progressions. The progressive DNA damage due to age and tumoral conditions was confirmed by raised levels of 5′S-cdG and 5′S-cdA. In the brain, the remodeling involved a diminution of palmitic acid accompanied by an increase in arachidonic acid, along both age and tumor progressions, causing increases in the unsaturation index, the peroxidation index, and total TFA as indicators of increased oxidative and free radical reactivity. Our results contribute to the ongoing debate on the central role of DNA and genome instability in the aging process, and on the need for a holistic vision, which implies choosing the best biomarkers for such monitoring. Furthermore, our data highlight brain tissue for its lipid remodeling response and inflammatory signaling, which seem to prevail over the effects of DNA damage.

Keywords

• tumor-bearing mice
• aging
• hydroxyl radical
• oxidatively-induced DNA lesions
• brain fatty acids
• age-induced remodeling