Structural and functional injury in minipig salivary glands following fractionated exposure to 70 Gy of ionizing radiation: an animal model for human radiation-induced salivary gland injury

doi:10.1016/S1079-2104(03)00369-X

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology

Volume 96, Issue 3, September 2003, Pages 267-274

https://doi.org/10.1016/S1079-2104(03)00369-X Get rights and content

Abstract

This study explored the feasibility of developing an animal model for radiation-induced salivary gland injury with a radiation protocol identical to current clinical practice. Three male Hanford minipigs were subjected to fractionated daily irradiation with a total dose of 70 Gy; structural and functional measures were compared with those of a control group of minipigs. We found that irradiated submandibular and parotid glands were one-third to one-half the gross size of control glands. Whereas no pathologic changes were noted in control glands, irradiated glands consistently demonstrated significant parenchymal loss with extensive acinar atrophy and interstitial fibrosis, enlarged nuclei in remaining acinar cells, and ductal dilatation and proliferation. Stimulated salivary flow was reduced by 81% in irradiated animals compared with preirradiation flow (P < .001); salivary flow in the control group increased by 30% during the same period (P < .001). The observed radiation-induced structural and functional salivary gland changes are comparable in every respect to those observed following irradiation of human salivary glands.

Section snippets

Irradiation protocol

Five male Hanford minipigs, ages 2 to 4 months with an initial body weight of 6 to 12 kg (Charles River Laboratories, Wilmington, Me) were used in this study. The protocol was approved by the Institutional Animal Care and Use Committee at the University of Medicine and Dentistry of New Jersey. Three minipigs were randomly assigned to an experimental group and 2 to a control group. All animals were housed together, were fed dry chow twice daily, were provided water upon demand, and received a

Body weight

All animals gained weight during the irradiation period. Irradiated animals gained 142% of their preradiation weight (pre: 16.3 ± 7.5 kg; post: 39.6 ± 4.7 kg), and control animals gained 156% of their preradiation weight (pre: 18.5 ± 9.1 kg; post: 47.5 ± 3.5 kg). The 14% difference in weight gain was not statistically significant.

Salivary quantity

There was no significant difference in saliva quantity between control and experimental animals before irradiation (6.74 ± 1.5 g vs 6.8 ± 1.72 g, respectively).

Discussion

Radiation-induced xerostomia is a painful, distressing, and potentially debilitating condition that head and neck cancer patients must endure for the rest of their lives. Oral, dental, and nutritional health is often compromised by radiation treatment. Functional salivary changes are directly related to the histologic changes.¹³ Numerous investigators have described the nature of salivary gland damage after irradiation in different animals such as rat,14, 15, 20 rabbit,16, 22 and monkey.17, 18,

Conclusion

This study demonstrates that the minipig is a suitable animal model for the study of functional and structural salivary gland injury resulting from an irradiation protocol identical to that used in the treatment of human oropharyngeal carcinoma. The observed functional and structural changes are comparable to those changes observed in humans undergoing radiation therapy in orofacial region. The minipig model, using fractionated irradiation to 70 cGy, may provide a more realistic biologic

Acknowledgements

We thank Dr D. Cleveland, oral pathologist, for her special assistance in pathology section.

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Oral medicineStructural and functional injury in minipig salivary glands following fractionated exposure to 70 Gy of ionizing radiation: an animal model for human radiation-induced salivary gland injury

Abstract

Section snippets

Irradiation protocol

Body weight

Salivary quantity

Discussion

Conclusion

Acknowledgements

Int J Radiat Oncol Biol Phys

J Am Dent Assoc

Int J Radiat Oncol Biol Phys

Oral Surg Oral Med Oral Pathol

Int J Radiat Oncol Biol Phys

Radiother Oncol

Radiother Oncol

Int J Radiat Oncol Biol Phys

Arch Oral Biol

J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiation-induced xerostomia in cancer patients. Effect on salivary and serum electrolytes

Cancer

Oral complications of cancer therapies. Pretherapy interventions to modify salivary dysfunction

NCI Monogr

Parotid sparing study in head and neck cancer patients receiving bilateral radiation therapyone-year results

J Dent Res

Conformal and intensity modulated irradiation of head and neck cancerthe potential for improved target irradiation, salivary gland function, and quality of life

Acta Otorhinolaryngol Belg

A phase II trial of subcutaneous amifostine and radiation therapy in patients with head and neck cancer

Semin Radiat Oncol

Morphologic and histochemical studies on the differing radiosensitivity of ductular and acinar cells of the rat submandibular gland

Virchows Arch B Cell Pathol Incl Mol Pathol

Influence on rabbit submandibular gland injury by stimulation or inhibition of gland function during irradiation. Histology and morphometry after 15 gray

Ann Otol Rhinol Laryngol

Oral medicine
Structural and functional injury in minipig salivary glands following fractionated exposure to 70 Gy of ionizing radiation: an animal model for human radiation-induced salivary gland injury