Insulin-Like Growth Factor-1 Preserves Salivary Gland Function After Fractionated Radiation
- Department of Physiological Sciences, University of Arizona, Tucson, AZ (United States)
- Department of Nutritional Sciences, University of Arizona, Tucson, AZ (United States)
- Department of Pathology, University of Arizona, Tucson, AZ (United States)
Purpose: Radiotherapy for head-and-neck cancer consists of fractionated radiation treatments that cause significant damage to salivary glands leading to chronic salivary gland dysfunction with only limited prevention and treatment options currently available. This study examines the feasibility of IGF-1 in preserving salivary gland function following a fractionated radiation treatment regimen in a pre-clinical model. Methods and Materials: Mice were exposed to fractionated radiation, and salivary gland function and histological analyses of structure, apoptosis, and proliferation were evaluated. Results: In this study, we report that treatment with fractionated doses of radiation results in a significant level of apoptotic cells in FVB mice after each fraction, which is significantly decreased in transgenic mice expressing a constitutively active mutant of Akt1 (myr-Akt1). Salivary gland function is significantly reduced in FVB mice exposed to fractionated radiation; however, myr-Akt1 transgenic mice maintain salivary function under the same treatment conditions. Injection into FVB mice of recombinant insulin-like growth factor-1 (IGF-1), which activates endogenous Akt, suppressed acute apoptosis and preserved salivary gland function after fractionated doses of radiation 30 to 90 days after treatment. FVB mice exposed to fractionated radiation had significantly lower levels of proliferating cell nuclear antigen-positive salivary acinar cells 90 days after treatment, which correlated with a chronic loss of function. In contrast, FVB mice injected with IGF-1 before each radiation treatment exhibited acinar cell proliferation rates similar to those of untreated controls. Conclusion: These studies suggest that activation of IGF-1-mediated pathways before head-and-neck radiation could modulate radiation-induced salivary gland dysfunction and maintain glandular homeostasis.
- OSTI ID:
- 21436201
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 2 Vol. 78; ISSN IOBPD3; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANIMALS
APOPTOSIS
BODY
CELL PROLIFERATION
DISEASES
FRACTIONATED IRRADIATION
GLANDS
GROWTH FACTORS
HEAD
HOMEOSTASIS
HORMONES
INSULIN
IRRADIATION
MAMMALS
MEDICINE
MICE
MITOGENS
NECK
NEOPLASMS
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PROTEINS
RADIOLOGY
RADIOTHERAPY
RODENTS
SALIVARY GLANDS
THERAPY
TRANSGENIC ANIMALS
TRANSGENIC MICE
VERTEBRATES