Juvkam, I. S. | bioRxiv Science

bioRxiv2022

A Preclinical Model to Investigate Normal Tissue Damage Following Fractionated Radiotherapy to the Head and Neck

Radiotherapy of head and neck cancer is known to cause both early and late-occurring toxicities. To better appraise normal tissue responses and their dependence on treatment parameters such as radiation field and type, as well as dose and fractionation scheme, a preclinical model with relevant endpoints is required. 12-week old female C57BL/6J mice were irradiated with 100 or 180 kV X-rays to total doses ranging from 30 to 85 Gy, given in 10 fractions over 5 days. The radiation field covered the oral cavity, swallowing structures, and salivary glands. Monte Carlo simulations were employed to estimate tissue dose distribution. The follow-up period was 35 days, in order to study the early radiation-induced effects. Baseline and post irradiation investigations included macroscopic and microscopic examinations of the skin, lips, salivary glands, and oral mucosa. Saliva sampling was performed to assess the salivary gland function following radiation exposure. A dose dependent radiation dermatitis in the skin was observed for doses above 30 Gy. Oral mucositis in the tongue appeared as ulcerations on the ventral surface of the tongue for doses of 75-85 Gy. The irradiated mice showed significantly reduced saliva production compared to controls. In summary, a preclinical model to investigate a broad panel of normal tissue responses following fractionated irradiation of the head and neck region was established. The optimal dose to study early radiation-induced effects was found to be around 75 Gy, as this was the highest tolerated dose that gave acute effects similar to what is observed in cancer patients.

cancer biology↗

bioRxiv2021

A juvenile climbing exercise establishes a muscle memory boosting the effects of exercise in adult rats

One of the ideas stemming from the discovery of a cellular memory in muscle cells has been that an early exercise period could induce a long-term muscle memory, boosting the effects of exercise later in life. In general muscles are more plastic in younger animals, so we devised a 5-week climbing exercise scheme with food reward administered to juvenile rats (post-natal week 4-9). The juvenile exercise increased fiber cross-sectional area (fCSA), and boosted nuclear accretion. Subsequently the animals were subjected to 10 weeks of detraining (week 9-19, standard caging). During this period fCSA became similar in the animals that had been climbing compared to Naive controls, but the elevated number of myonuclei induced by the climbing were maintained. When the Naive rats were subjected to two weeks of adult exercise (week 19-21) there was little effect on fCSA, while the previously trained rats displayed an increase of 19%. Similarly, when the rats were subjected to unilateral surgical overload in lieu of the adult climbing exercise, the increase in fCSA was 20% (juvenile climbing group) and 11% (Naive rats) compared to the contralateral leg. This demonstrated that juvenile exercise can establish a muscle memory. The juvenile climbing exercise with food reward led to leaner animals with lower body weight. These differences were to some extent maintained throughout the adult detraining period in spite of all animals being fed ad libitum, indicating a form of body weight memory.

physiology↗