Sleep Fragmentation Accelerates Carcinogenesis in a Chemical-Induced Colon Cancer Model

Abstract

Aims of this study were to test whether sleep fragmentation (SF) increased carcinogenesis and to investigate the possible mechanisms of carcinogenesis in a chemical-induced colon cancer model. In this study, eight-week-old C57BL/6 mice were divided into Home cage (HC) and SF groups. After the azoxymethane (AOM) injection, the mice in the SF group were subjected to SF for 77 days. SF was accomplished in a sleep fragmentation chamber. In the second protocol, mice were divided into 2% dextran sodium sulfate (DSS)-treated, HC, and SF groups and were exposed to the HC or SF procedures. Immunohistochemical and immunofluorescent stainings were conducted to determine the level of 8-OHdG and reactive oxygen species (ROS), respectively. Quantitative real-time polymerase chain reaction was used to assess the relative expression of inflammatory and ROS-generating genes. The number of tumors and average tumor size were significantly higher in the SF group than in the HC group. The intensity (%) of the 8-OHdG stained area was significantly higher in the SF group than in the HC group. The fluorescence intensity of ROS was significantly higher in the SF group than the HC group. SF accelerated cancer development in a murine AOM/DSS-induced model of colon cancer, and the increased carcinogenesis was associated with ROS- and oxidative stress-induced DNA damage.

The Burden of Comorbidities in Obstructive Sleep Apnea and the Pathophysiologic Mechanisms and Effects of CPAP

“…The reduced antitumor activity and enhanced immunosuppression were found as a result of an experimental cell-culture and mice-model study [ 90 ]. Short sleep duration was found to be associated with alterations in tumor-associated macrophage (TAM) phenotypes, specifically higher TLR4 expression, which plays an important role in tumor progression [ 91 ]; moreover, an experimental animal model of colon cancer study determined a certain relationship between the impact of sleep fragmentation and ROS-induced DNA damage, which in turn leads to cancerogenesis [ 92 ].…”

Objectively measured peri-vaccination sleep does not predict COVID-19 breakthrough infection

“…An increased awakening frequency likely reflects decreased sleep consolidation (or more fragmented sleep), which would suggest a more unstable sleep architecture and has also been correlated with subjectively reported lower quality sleep 27 . In murine models, highly fragmented sleep has been implicated in abnormal hematopoiesis of immune progenitor cells 28 , and is associated with increased cancer cell growth 29 , 30 . Sleep fragmentation is also associated with an increased incidence of Alzheimer’s disease, possibly through aging of microglia, which play an important role in innate and adaptive immune responses for neurons 31 , 32 .…”

Melatonin Improves Glucose Homeostasis and Insulin Sensitivity by Mitigating Inflammation and Activating AMPK Signaling in a Mouse Model of Sleep Fragmentation

“…Mice were maintained on a normal chow diet and housed in a controlled environment with a regular 12 h light–dark cycle at a constant temperature (24 ± 2 °C) and ad libitum access to food and water. Mice were randomly divided into three groups: control mice ( n = 10), mice housed in standard housing conditions and sleep fragmented (SF, n = 10), and melatonin-treated SF mice (SF+Mel, n = 10) housed in an SF chamber as described previously (model 80391; Lafayette Instrument, Lafayette, IN, USA) [ 19 ]. Due to limitations on blood volume and adipose tissue size, we used separate sets of mice to study glycemic response and reactive oxygen species (ROS) detection on adipose tissue stromal vascular fraction (SVF).…”

“…The SF group and SF+Mel group mice were exposed to SF for 12 weeks. The machine used to induce sleep fragmentation has previously been described [ 19 , 20 ]. In brief, the timer of the moving sweep bar was set for mice with severe sleep apnea, waking more than 30 times per hour.…”