Effects of ionizing irradiation and β-adrenergic stimulation on gene expression pattern in rat submandibular glands

R. M. Nagler, A. Nagler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Radiotherapy administrated to patients wit head and neck malignancies and prior to bone marrow transplantation often results in severe xerostomia. We evaluated the expression of early response proto-oncogens (c-fos and jun B), tissue specific genes (proline rich protein [PRP] and killikrein), and proteolysis linked utiquitin gene following exposure the 15 Gy irradiation alone or in combination with β-adrenergic stimulation of the rat submandibular glands. Head and neck irradiation resulted not only in dysfunction and tissue loss of the salivary gland but also in a systemic effect expressed as profound body weight loss. Irradiation alone was not found to induce expression of the jun B but not the c-fos proto-oncogenes. The combination of irradiation and β-adrenergic stimulation by isoproterenol induced earlier expression jun B and profound expression of the c-fos proto-oncogene in comparison to irradiation alone. In contrast, the kallikrein and ubiquitin genes were expressed constitutively and were not affected by irradiation alone or in combination with β-adrenergic stimulation. In addition, irradiation had no effect on submandibular gland mRNA translation. We observed that the expression of the gene whose regulation is associated with DNA damage (i.e. jun B and c-fos) was enhanced by irradiation alone or in combination with isoproterenol administration. In contrast, the expression of genes associated with the routine functional integrity of the cell (i.e. kallikrein, ubiquitin, and PRP) was unaffected. These finding, in addition to delayed gland dysfunction, leads us to believe that the irradiation induced injury to the submandibular glands is to be attributed to reproductive stem cell death which may be partly obliterated in the clinical setting by better understanding.

Original languageEnglish
Pages (from-to)2749-2756
Number of pages8
JournalAnticancer Research
Volume16
Issue number5 A
StatePublished - Sep 1996
Externally publishedYes

Keywords

  • Gene expression b-adrenergic
  • Ionizing irradiation
  • Proto-oncogenes
  • Salivary glands
  • Tissue specific genes
  • Ubiquitin gene
  • c-fos
  • jun β

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