Abstract
Undesirable exposure of diaphragm to radiation during thoracic radiation therapy has not been fully considered over the past decades. Our study aims to examine the potential biological effects on diaphragm induced by radiation. One-time ionizing irradiation of 10 Gy was applied either to the diaphragmatic region of mice or to the cultured C2C12 myocytes. Each sample was then assayed for muscle function, oxidative stress, or cell viability on days 1, 3, 5, and 7 after irradiation. Our mouse model shows that radiation significantly reduced muscle function on the 5th and 7th days and increased reactive oxygen species (ROS) formation in the diaphragm tissue from days 3 to 7. Similarly, the myocytes exhibited markedly decreased viability and elevated oxidative stress from days 5 to 7 after radiation. These data together suggested that a single dose of 10-Gy radiation is sufficient to cause acute adverse effects on diaphragmatic muscle function, redox balance, and myocyte survival. Furthermore, using the collected data, we developed a physical model to formularize the correlation between diaphragmatic ROS release and time after irradiation, which can be used to predict the biological effects of radiation with a specific dosage. Our findings highlight the importance of developing protective strategies to attenuate oxidative stress and prevent diaphragm injury during radiotherapy.
Highlights
Radiation therapy (RT) is one of the three major treatment options for cancers
There was no significant difference between Ionizing radiation (IR) and control groups in terms of fatigue tolerance on days 1 and 3 (Figures 1D,E)
Our animal and cell radiation models suggest that 10-Gy IR exposure is sufficient to induce short-term muscle fatigue, cell death, and oxidative stress in the diaphragm
Summary
Radiation therapy (RT) is one of the three major treatment options (surgery, chemotherapy, RT) for cancers. The primary side effect associated with RT can be unintentional radiation damage to normal tissues and organs surrounding the tumor target (Stewart and Fajardo, 1971; Van Der Kogel and Barendse, 1974; Hishikawa et al, 1984; Delanian et al, 1994; Dunlap et al, 2010). Breast cancer, and stomach cancer are among the most commonly diagnosed and lethal cancers worldwide (Ferlay et al, 2010; Torre et al, 2015). For those patients, radiation treatment can potentially damage the chest wall and diaphragm.
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