Department of Health and Safety Convergence Science, Graduate School, Korea University, Seoul 02841, Republic of Korea.
Sleep Medicine Institute, Jungwon University, Goesan-gun 20204, Chungcheongbuk-do, Republic of Korea.
Int J Mol Sci. 2023 Feb 25;24(5):4547. doi: 10.3390/ijms24054547.
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.
本研究旨在探讨睡眠片段化（SF）是否会促进致癌作用，并研究化学诱导结肠癌模型中致癌作用的可能机制。在这项研究中，将 8 周龄的 C57BL/6 小鼠分为普通笼（HC）和 SF 组。在给予氧化偶氮甲烷（AOM）注射后，SF 组的小鼠接受 SF 处理 77 天。SF 通过睡眠片段化室实现。在第二个方案中，将小鼠分为 2%葡聚糖硫酸钠（DSS）处理组、HC 组和 SF 组，并分别暴露于 HC 或 SF 程序中。通过免疫组织化学和免疫荧光染色分别确定 8-OHdG 和活性氧（ROS）的水平。通过定量实时聚合酶链反应评估炎症和 ROS 生成基因的相对表达。SF 组的肿瘤数量和平均肿瘤大小明显高于 HC 组。SF 组中 8-OHdG 染色区域的强度（%）明显高于 HC 组。SF 组的 ROS 荧光强度明显高于 HC 组。SF 加速了 AOM/DSS 诱导的小鼠结肠癌模型中的癌症发展，并且致癌作用的增加与 ROS 和氧化应激诱导的 DNA 损伤有关。
