Nagler R M, Nagler A
Oral Radiology Department, Hadassah University Hospital, Jerusalem, Israel.
Anticancer Res. 1996 Sep-Oct;16(5A):2749-56.
Radiotherapy administrated to patients with head and neck malignancies and prior to bone marrow transplantation often results in severe xerostomia. We evaluated the expression of early response proto-oncogenes (c-fos and jun B), tissue specific genes (proline rich protein [PRP] and kallikrein), and proteolysis linked utiquitin gene following exposure to 15 Gy irradiation alone or in combination with beta-adrenergic stimulation of the rat submandibular glands. Head and neck irradiation resulted not only in dysfunction and tissue loss of the salivary glands but also in a systemic effect expressed as profound body weight loss. Irradiation alone was found to induce expression of the jun B but not the c-fos proto-oncogenes. The combination of irradiation and beta-adrenergic stimulation by isoproterenol induced earlier expression of 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 beta-adrenergic stimulation. In addition, irradiation had no effect on submandibular gland mRNA translation. We observed that the expression of the genes 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 findings, 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.
对头颈部恶性肿瘤患者在进行骨髓移植之前进行放疗，常常会导致严重的口干症。我们评估了单独暴露于15 Gy辐射或联合β-肾上腺素能刺激大鼠下颌下腺后，早期反应原癌基因（c-fos和jun B）、组织特异性基因（富含脯氨酸蛋白[PRP]和激肽释放酶）以及与蛋白水解相关的泛素基因的表达情况。头颈部放疗不仅导致唾液腺功能障碍和组织损失，还产生了全身性影响，表现为体重显著减轻。单独照射发现可诱导jun B基因表达，但不能诱导c-fos原癌基因表达。与单独照射相比，照射与异丙肾上腺素β-肾上腺素能刺激联合使用可诱导jun B基因更早表达以及c-fos原癌基因的强烈表达。相比之下，激肽释放酶和泛素基因持续表达，不受单独照射或联合β-肾上腺素能刺激的影响。此外，照射对下颌下腺mRNA翻译没有影响。我们观察到，单独照射或联合异丙肾上腺素给药可增强其表达受DNA损伤调控的基因（即jun B和c-fos）的表达。相比之下，与细胞常规功能完整性相关的基因（即激肽释放酶、泛素和PRP）的表达未受影响。这些发现，除了延迟的腺体功能障碍外，使我们相信照射诱导的下颌下腺损伤归因于生殖干细胞死亡，通过更好的理解在临床环境中这种情况可能会部分消除。
