Stable Acinar Progenitor Cell Model Identifies Treacle-Dependent Radioresistance

Details

• Personal Author:
  Chrisler WB ; Gritsenko MA ; Hu D ; Qian W-J ; Smith JN ; Timchalk C ; Weber TJ
• Description:
  Radiotherapy for head and neck cancers can result in extensive damage to the salivary glands, significantly affecting patient quality of life. However, the salivary gland can recover in patients receiving lower doses of radiation. In addition, there is considerable interest in delineating the mechanisms by which stem cells survive radiation exposure and promote tissue regeneration. In this study, we isolated stable radioresistant acinar progenitor cells from the submaxillary gland of the Sprague Dawley rat. Progenitor cells are characterized as c-Kithigh/alpha-amylase+ and are resistant to X rays (=5 Gy).We further isolated a radiosensitive acinar counterpart, characterized as c-Kitlow/alpha-amylase+, which is effectively killed by exposure to 2 Gy X ray of radiation. Phosphopeptides with homology to the treacle protein (TCOF1) were disproportionately increased in progenitor cells, compared to their radiosensitive counterparts. Silencing of TCOF1 expression (shRNA) radiosensitized progenitor cells, a response conserved in human cells with TCOF1 knockdown. Collectively, these observations indicate that radiation resistance is an intrinsic property of c-Kithigh salivary gland progenitor cells. Since human salivary gland stem cells with c-Kit expression are believed to have enhanced regenerative potencies, our model system provides a stable platform to investigate molecular features associated with c-Kit expression that may contribute to protection or stabilization of the stem cell niche. [Description provided by NIOSH]
• Subjects:
  Animals Environmental Exposure Laboratories Neoplasms Occupational Health Risk Assessment Risk Factors Safety
• Keywords:
  Cancer Exposure Levels Laboratory Animals Models Proteins Radiation Therapy Risk Factors Salivary Glands Stem Cells
• ISSN:
  0033-7587
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 10 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  135-144
• Volume:
  192
• Issue:
  2
• NIOSHTIC Number:
  nn:20057527
• Citation:
  Radiat Res 2019 Aug; 192(2):135-144
• Contact Point Address:
  Thomas J. Weber, 902 Battelle Blvd., J4-02, Pacific Northwest National Laboratory, Richland, WA 99354
• Email:
  Thomas.Weber@pnnl.gov
• Federal Fiscal Year:
  2019
• Performing Organization:
  Battelle Pacific Northwest Laboratory
• Peer Reviewed:
  True
• Start Date:
  20060901
• Source Full Name:
  Radiation Research
• End Date:
  20170831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:49dfc623dd3ccfcebc51a74dccef5ce4aace58dd9595ecd1d24fe9c83a135b1cf72d30301396ae34ed260624bfae14d4f0c6aab5be18e4e7145926291f8ea027
• Download URL:
  https://stacks.cdc.gov/view/cdc/214855/cdc_214855_DS1.pdf
• File Type:
  [PDF - 2.31 MB ]