Exploring the Relationship Between Tissue, Cellular and Cell-free mtDNA Content in a Murine Model of Cancer-Related Fatigue

Cancer-related fatigue impacts daily activity and quality of life of cancer patients. While variability exists, the majority of studies report 30-60% prevalence of moderate to severe fatigue in patient populations. Inflammation has often been associated with CRF, but recent research indicates metabolic dysfunction may be a mediator between inflammation and CRF. The present study aims at using the murine Lewis lung carcinoma (LLC) model and cisplatin chemotherapy to investigate the long-term effects of cancer and cancer treatment on mitochondrial DNA content and explore its relationship to fatigue- like behavior. As anticipated, tumor-bearing and cisplatin treated mice showed fatigue-like behavior as assessed by decreased voluntary wheel running. Peripheral blood mononuclear cells (PBMCs) mtDNA content was decreased in tumor-bearing mice, which was negatively correlated with their fatigue-like behavior. While cisplatin decreased liver mtDNA content, it did not correlate to fatigue. Furthermore, Kidney and PBMCs mtDNA levels were correlated. These results provide complementary evidence in support of a relationship between PBMC mtDNA content and fatigue.