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bioRxiv · 10.1101/2020.05.26.117937

Distinct Long-term Effects of Precision X-Radiation on Reflex Saliva Flow Rate and Tissue Integrity in a Preclinical Model of Chronic Hyposalivation

Aalam, S. M. M.·Viringipurampeer, I. A.·Walb, M. C.·Tryggestad, E. J.·Emperumal, C. P.·Song, J.·Xu, X.·Saini, R.·Lombaert, I. M. A.·Sarkaria, J. N.·Garcia, J.·Janus, J. R.·Kannan, N.
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Abstract

Chronic salivary hypofunction and xerostomia are common side effects of radiation therapy which is an essential component in the curative management in patients with head & neck cancers. Over the years, improvements in delivery techniques such as image-guided intensity modulated radiation therapy have led to improvement in cancer management but chronic hyposalivation continues to be a challenge that causes long-term health implications resulting in compromised quality of life. Recent advances in salivary stem cell research promise new frontier in the treatment of radiation-induced hyposalivation by initiating regeneration of radiation-damaged salivary parenchymal cells. Lack of a standard preclinical immunodeficient model to assess radiation-induced changes objectively and quantitatively in salivary flow rates will impede rapid progress towards the development of cellular therapies for chronic salivary dysfunction and attendant xerostomia. Herein, we report the first fully characterized novel cone-beam computed tomography (CBCT)-guided precision ionizing radiation (IR) induced chronic hyposalivation model in radiosensitive, immunodeficient transgenic NSG-SGM3 mice expressing three human cytokines including c-KIT ligand/stem cell factor. Additionally, we also report a novel and instantaneous method to objectively assess the kinetics of pilocarpine-stimulated salivary flowrate. Comprehensive structural and functional characterization of salivary glands revealed previously unknown and highly complex gender, age, IR dose and salivary gland subtype-specific effects of salivary-ablative precision IR.Competing Interest StatementThe authors have declared no competing interest.View Full Text

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Aalam, S. M. M., Viringipurampeer, I. A., Walb, M. C., Tryggestad, E. J., Emperumal, C. P., Song, J., Xu, X., Saini, R., Lombaert, I. M. A., Sarkaria, J. N., Garcia, J., Janus, J. R., Kannan, N.. 2020-05-30. Distinct Long-term Effects of Precision X-Radiation on Reflex Saliva Flow Rate and Tissue Integrity in a Preclinical Model of Chronic Hyposalivation. https://doi.org/10.1101/2020.05.26.117937

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