Early and Late Effects of X-Irradiation on Submandibular Gland: A Morphological Study in Mice

Urek, Miranda Muhvić; Bralić, Marina; Tomac, Jelena; Borčić, Josipa; Uhač, Ivone; Glažar, Irena; Robert, Aymeric; Ferreri, Silvio

doi:10.1016/j.arcmed.2005.03.005

Cited by 34 publications

(36 citation statements)

References 22 publications

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“…In rodent models, changes in sucrose and sodium taste behavioral preferences are also detectable in the first and second weeks following radiation (Yamazaki et al, 2009; Nelson, 1998). However, these studies each entailed delivery of 15–17 Gy to the head, which can cause widespread tissue damage; thus in addition to targeting mitotic progenitors, post-mitotic taste cells may also have been damaged directly (Shatzman and Mossman, 1982; Urek et al, 2005; and see Figure 1 in Yamazaki et al, 2009). …”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Taste Bud Cell Loss after Head and Neck Irradiation

Nguyen¹,

Reyland²,

Barlow³

2012

J. Neurosci.

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Taste loss in human patients following radiotherapy for head and neck cancer is a common and significant problem, but the cellular mechanisms underlying this loss are not understood. Taste stimuli are transduced by receptor cells within taste buds, and like epidermal cells, taste cells are regularly replaced throughout adult life. This renewal relies on a progenitor cells adjacent to taste buds, which continually supply new cells to each bud. Here we treated adult mice with a single 8 Gy dose of X-ray irradiation to the head and neck, and analyzed taste epithelium at 1–21 days post-irradiation (dpi). We found irradiation targets the taste progenitor cells, which undergo cell cycle arrest (1–3 dpi) and apoptosis (within 1 dpi). Taste progenitors resume proliferation at 5–7 dpi, with the proportion of cells in S and M phase exceeding control levels at 5–6 and 6 dpi, respectively, suggesting that proliferation is accelerated and/or synchronized following radiation damage. Using BrdU birthdating to identify newborn cells, we found that the decreased proliferation following irradiation reduces the influx of cells at 1–2 dpi, while the robust proliferation detected at 6 dpi accelerates entry of new cells into taste buds. By contrast, the number of differentiated taste cells was not significantly reduced until 7 dpi. These data suggest a model where continued natural taste cell death, paired with temporary interruption of cell replacement underlies taste loss after irradiation.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of Taste Bud Cell Loss after Head and Neck Irradiation

Nguyen¹,

Reyland²,

Barlow³

2012

J. Neurosci.

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“…We believe this finding can be explained, first, due to a further loss of acinar cells during the late-effect phase post-IR, and second, that the therapeutic effect was at its peak during the six bi-weekly injections of BMDCs post-IR. First, radiation to salivary gland causes a loss of acinar cells during the late-effect phase post-IR (Urek et al, 2005; Zeilstra et al, 2000). Prominent acinar cells loss was reported 90 days (13 weeks) after irradiation in mouse submandibular glands.…”

Section: Discussionmentioning

confidence: 99%

“…Prominent acinar cells loss was reported 90 days (13 weeks) after irradiation in mouse submandibular glands. Urek et al (2005) speculated that radiation-induced sublethal-DNA damage became apparent during the late-effect phase post-IR due to a slow cell turnover rate. Furthermore, Feng et al (2009) reported that human salivary glands continued to show a severe reduction in the number of acinar cells even 15 years after radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

Bone marrow-derived cells rescue salivary gland function in mice with head and neck irradiation

Sumita

Liu

Khalili

et al. 2011

The International Journal of Biochemistry & Cell Biology

126

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Treatment for most patients with head and neck cancers includes ionizing radiation. A consequence of this treatment is irreversible damage to salivary glands (SGs), which is accompanied by a loss of fluid-secreting acinar-cells and a considerable decrease of saliva output. While there are currently no adequate conventional treatments for this condition, cell-based therapies are receiving increasing attention to regenerate SGs. In this study, we investigated whether bone marrow-derived cells (BMDCs) can differentiate into salivary epithelial cells and restore SG function in head and neck irradiated mice. BMDCs from male mice were transplanted into the tail-vein of 18 Gy-irradiated female mice. Salivary output was increased in mice that received BMDCs transplantation at week 8 and 24 post-irradiation. At 24 weeks after irradiation (IR), harvested SGs (submandibular and parotid glands) of BMDC-treated mice had greater weights than those of non-treated mice. Histological analysis shows that SGs of treated mice demonstrated an increased level of tissue regenerative activity such as blood vessel formation and cell proliferation, while apoptotic activity was increased in non-transplanted mice. The expression of stem cell markers (Sca-1 or c-kit) was detected in BMDC-treated SGs. Finally, we detected an increased ratio of acinar-cell area and approximately 9% of Y-chromosome-positive (donor-derived) salivary epithelial cells in BMDC-treated mice. We propose here that cell therapy using BMDCs can rescue the functional damage of irradiated SGs by direct differentiation of donor BMDCs into salivary epithelial cells.

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“…However, apoptosis induced by radiation has also been reported to show no correlation with salivary dysfunction in the early stages after irradiation 16. Although the peak in the number of apoptotic cells and hyposalivation are observed a few days after irradiation, acinar cell loss is not readily detectable at this time 17. Radiation‐induced dysfunction in normal tissue is thought to be caused by the loss of cell renewal due to DNA damage in progenitor cells and stem cells; thus tissues with rapid cell turnover are highly sensitive to radiation‐induced damage.…”

Section: Discussionmentioning

confidence: 99%

“…DNA damage to progenitor cells or stem cells therefore is not considered to be responsible for the acute dysfunction of the salivary glands after irradiation 18, 19. Apoptosis, however, has the potential to cause the loss of acinar cells during the late phase 17. This suggests that although it may be difficult to prevent early salivary gland disorders, even if apoptosis can be suppressed, it may be possible to restore the function of salivary glands by aiding the regeneration of acinar cells.…”

Section: Discussionmentioning

confidence: 99%