# Radiation-induced Salivary Gland Vascular Injury: Mechanisms and Interventions

> **NIH NIH R56** · ROSWELL PARK CANCER INSTITUTE CORP · 2022 · $471,502

## Abstract

Project Summary
Radiation-induced xerostomia (RIX) is the most frequent and permanent late side-effect of RT in head and
neck cancer patients that leads to compromised speech, difficulty in eating and swallowing and an overall
reduction in quality of life in patients. Sadly, no definitive therapy or effective mitigating strategy is available for
routine clinical management of RIX. The development of safe and effective strategies to mitigate RIX has been
hindered by limited mechanistic insight and lack of objective methods to characterize the trajectory of normal
tissue injury. In this regard, our preclinical studies have revealed that the temporal evolution of radiation-
induced vascular injury and DNA damage response is influenced by the host immune status. Our preliminary
studies have also revealed that vitamin D (VitD) deficiency exacerbates radiation-induced vascular injury in
vivo. Conversely, VitD treatment protects salivary glands from radiation injury in 3D organoids. These
observations along with the known anti-inflammatory and antioxidant effects of VitD have led us to hypothesize
that correction of VitD deficiency through diet or administration of the active metabolite, calcitriol, can protect
salivary glands from radiation damage and alleviate RIX in vivo. To test these hypotheses, we propose to
characterize the dynamic changes in vascularity and immune profiles of salivary glands in response to
radiotherapy in mice (Aim 1) and evaluate the impact of VitD on preventing/mitigating RIX (Aim 2). A preclinical
large animal trial to examine the effects of VitD on response of head and neck tumors and salivary glands to
volumetric modulated arc therapy is also proposed (Aim 3). Using novel experimental models and imaging
technologies, the application will systematically examine the vascular and immune mechanisms underlying
salivary gland radiation injury and define the therapeutic potential of VitD as a radioprotective agent. The
proposed studies will enable development of VitD supplementation regimens for prevention of RIX in head and
neck cancer patients in the near future.

## Key facts

- **NIH application ID:** 10701306
- **Project number:** 1R56DE032268-01
- **Recipient organization:** ROSWELL PARK CANCER INSTITUTE CORP
- **Principal Investigator:** Mukund Seshadri
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $471,502
- **Award type:** 1
- **Project period:** 2022-09-22 → 2024-09-21

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10701306

## Citation

> US National Institutes of Health, RePORTER application 10701306, Radiation-induced Salivary Gland Vascular Injury: Mechanisms and Interventions (1R56DE032268-01). Retrieved via AI Analytics 2026-06-24 from https://api.ai-analytics.org/grant/nih/10701306. Licensed CC0.

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