Morphometric and functional changes of salivary gland dysfunction after radioactive iodine ablation in a murine model

Jeong Seok Choi, In Suh Park, Seok Ki Kim, JaeYoul Lim, Young Mo Kim

Research output: Contribution to journalArticle

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Abstract

Background: Ablation of the thyroid tissue using radioactive iodine (RAI) after the surgical removal of well-differentiated thyroid cancer can induce radiation-related salivary gland (SG) dysfunction. However, in vivo changes of SGs after RAI administration in appropriate animal models are not well described in the literature. This study was undertaken to document morphometric and functional changes during the 12 months after RAI administration in a murine model of RAI-induced SG dysfunction. Methods: Four-week-old female C57BL/6 mice (n=60) were divided into an RAI-treated group (n=30) that received RAI orally (0.01 mCi/g body weight) and an unexposed control group (n=30). Mice in both groups were divided into five subgroups (n=6 per subgroup) and euthanized at 1, 2, 3, 6, and 12 months post-RAI administration. Salivary flow rates and salivary lag times were measured at 1, 2, 3, 6, and 12 months after RAI administration. Morphological and histological examinations and terminal deoxynucleotidyl transferase dUTP nick end labeling assays were performed. In addition, changes in salivary 99m Tc pertechnetate uptake and excretion were observed by single-photon emission computed tomography. Results: In RAI-treated mice, the SGs were significantly lighter than those of unexposed controls at all study time points. Lag times to salivation in the RAI-treated group were greater than in the unexposed controls, but mean salivary flow rates were lower. Histologic examinations of SGs in the RAI group showed pale cytoplasm, atypical ductal configuration, septal widening, cytoplasmic vacuolization with pleomorphism, lymphocyte infiltration, and increased fibrosis. Furthermore, more apoptotic cells were observed in acini and ducts in the RAI group. In addition, patterns of 99m Tc pertechnetate uptake and excretion in the RAI group were quite different from those observed in controls at 1 and 12 months post-RAI. Conclusion: Various histological alterations were observed in mice exposed to RAI, that is, an increase in apoptotic acini and ductal cells and functional SG deterioration. The murine model of RAI-induced SG dysfunction used in the present study appears to be applicable to preclinical research on RAI-induced sialadenitis in patients with well-differentiated thyroid cancer.

Original languageEnglish
Pages (from-to)1445-1451
Number of pages7
JournalThyroid
Volume23
Issue number11
DOIs
Publication statusPublished - 2013 Nov 1

Fingerprint

Salivary Glands
Iodine
Sodium Pertechnetate Tc 99m
Thyroid Neoplasms
Sialadenitis
Salivation
DNA Nucleotidylexotransferase
Acinar Cells
Single-Photon Emission-Computed Tomography
Inbred C57BL Mouse

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Choi, Jeong Seok ; Park, In Suh ; Kim, Seok Ki ; Lim, JaeYoul ; Kim, Young Mo. / Morphometric and functional changes of salivary gland dysfunction after radioactive iodine ablation in a murine model. In: Thyroid. 2013 ; Vol. 23, No. 11. pp. 1445-1451.
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abstract = "Background: Ablation of the thyroid tissue using radioactive iodine (RAI) after the surgical removal of well-differentiated thyroid cancer can induce radiation-related salivary gland (SG) dysfunction. However, in vivo changes of SGs after RAI administration in appropriate animal models are not well described in the literature. This study was undertaken to document morphometric and functional changes during the 12 months after RAI administration in a murine model of RAI-induced SG dysfunction. Methods: Four-week-old female C57BL/6 mice (n=60) were divided into an RAI-treated group (n=30) that received RAI orally (0.01 mCi/g body weight) and an unexposed control group (n=30). Mice in both groups were divided into five subgroups (n=6 per subgroup) and euthanized at 1, 2, 3, 6, and 12 months post-RAI administration. Salivary flow rates and salivary lag times were measured at 1, 2, 3, 6, and 12 months after RAI administration. Morphological and histological examinations and terminal deoxynucleotidyl transferase dUTP nick end labeling assays were performed. In addition, changes in salivary 99m Tc pertechnetate uptake and excretion were observed by single-photon emission computed tomography. Results: In RAI-treated mice, the SGs were significantly lighter than those of unexposed controls at all study time points. Lag times to salivation in the RAI-treated group were greater than in the unexposed controls, but mean salivary flow rates were lower. Histologic examinations of SGs in the RAI group showed pale cytoplasm, atypical ductal configuration, septal widening, cytoplasmic vacuolization with pleomorphism, lymphocyte infiltration, and increased fibrosis. Furthermore, more apoptotic cells were observed in acini and ducts in the RAI group. In addition, patterns of 99m Tc pertechnetate uptake and excretion in the RAI group were quite different from those observed in controls at 1 and 12 months post-RAI. Conclusion: Various histological alterations were observed in mice exposed to RAI, that is, an increase in apoptotic acini and ductal cells and functional SG deterioration. The murine model of RAI-induced SG dysfunction used in the present study appears to be applicable to preclinical research on RAI-induced sialadenitis in patients with well-differentiated thyroid cancer.",
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Morphometric and functional changes of salivary gland dysfunction after radioactive iodine ablation in a murine model. / Choi, Jeong Seok; Park, In Suh; Kim, Seok Ki; Lim, JaeYoul; Kim, Young Mo.

In: Thyroid, Vol. 23, No. 11, 01.11.2013, p. 1445-1451.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Morphometric and functional changes of salivary gland dysfunction after radioactive iodine ablation in a murine model

AU - Choi, Jeong Seok

AU - Park, In Suh

AU - Kim, Seok Ki

AU - Lim, JaeYoul

AU - Kim, Young Mo

PY - 2013/11/1

Y1 - 2013/11/1

N2 - Background: Ablation of the thyroid tissue using radioactive iodine (RAI) after the surgical removal of well-differentiated thyroid cancer can induce radiation-related salivary gland (SG) dysfunction. However, in vivo changes of SGs after RAI administration in appropriate animal models are not well described in the literature. This study was undertaken to document morphometric and functional changes during the 12 months after RAI administration in a murine model of RAI-induced SG dysfunction. Methods: Four-week-old female C57BL/6 mice (n=60) were divided into an RAI-treated group (n=30) that received RAI orally (0.01 mCi/g body weight) and an unexposed control group (n=30). Mice in both groups were divided into five subgroups (n=6 per subgroup) and euthanized at 1, 2, 3, 6, and 12 months post-RAI administration. Salivary flow rates and salivary lag times were measured at 1, 2, 3, 6, and 12 months after RAI administration. Morphological and histological examinations and terminal deoxynucleotidyl transferase dUTP nick end labeling assays were performed. In addition, changes in salivary 99m Tc pertechnetate uptake and excretion were observed by single-photon emission computed tomography. Results: In RAI-treated mice, the SGs were significantly lighter than those of unexposed controls at all study time points. Lag times to salivation in the RAI-treated group were greater than in the unexposed controls, but mean salivary flow rates were lower. Histologic examinations of SGs in the RAI group showed pale cytoplasm, atypical ductal configuration, septal widening, cytoplasmic vacuolization with pleomorphism, lymphocyte infiltration, and increased fibrosis. Furthermore, more apoptotic cells were observed in acini and ducts in the RAI group. In addition, patterns of 99m Tc pertechnetate uptake and excretion in the RAI group were quite different from those observed in controls at 1 and 12 months post-RAI. Conclusion: Various histological alterations were observed in mice exposed to RAI, that is, an increase in apoptotic acini and ductal cells and functional SG deterioration. The murine model of RAI-induced SG dysfunction used in the present study appears to be applicable to preclinical research on RAI-induced sialadenitis in patients with well-differentiated thyroid cancer.

AB - Background: Ablation of the thyroid tissue using radioactive iodine (RAI) after the surgical removal of well-differentiated thyroid cancer can induce radiation-related salivary gland (SG) dysfunction. However, in vivo changes of SGs after RAI administration in appropriate animal models are not well described in the literature. This study was undertaken to document morphometric and functional changes during the 12 months after RAI administration in a murine model of RAI-induced SG dysfunction. Methods: Four-week-old female C57BL/6 mice (n=60) were divided into an RAI-treated group (n=30) that received RAI orally (0.01 mCi/g body weight) and an unexposed control group (n=30). Mice in both groups were divided into five subgroups (n=6 per subgroup) and euthanized at 1, 2, 3, 6, and 12 months post-RAI administration. Salivary flow rates and salivary lag times were measured at 1, 2, 3, 6, and 12 months after RAI administration. Morphological and histological examinations and terminal deoxynucleotidyl transferase dUTP nick end labeling assays were performed. In addition, changes in salivary 99m Tc pertechnetate uptake and excretion were observed by single-photon emission computed tomography. Results: In RAI-treated mice, the SGs were significantly lighter than those of unexposed controls at all study time points. Lag times to salivation in the RAI-treated group were greater than in the unexposed controls, but mean salivary flow rates were lower. Histologic examinations of SGs in the RAI group showed pale cytoplasm, atypical ductal configuration, septal widening, cytoplasmic vacuolization with pleomorphism, lymphocyte infiltration, and increased fibrosis. Furthermore, more apoptotic cells were observed in acini and ducts in the RAI group. In addition, patterns of 99m Tc pertechnetate uptake and excretion in the RAI group were quite different from those observed in controls at 1 and 12 months post-RAI. Conclusion: Various histological alterations were observed in mice exposed to RAI, that is, an increase in apoptotic acini and ductal cells and functional SG deterioration. The murine model of RAI-induced SG dysfunction used in the present study appears to be applicable to preclinical research on RAI-induced sialadenitis in patients with well-differentiated thyroid cancer.

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