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大鼠下颌下腺导管细胞和腺泡细胞放射敏感性差异的形态学和组织化学研究

Morphologic and histochemical studies on the differing radiosensitivity of ductular and acinar cells of the rat submandibular gland.

作者信息

Abok K, Brunk U, Jung B, Ericsson J

出版信息

Virchows Arch B Cell Pathol Incl Mol Pathol. 1984;45(4):443-60. doi: 10.1007/BF02889885.

DOI:10.1007/BF02889885
PMID:6145251
Abstract

The submandibular glands of male rats were exposed to 50 Gy X-irradiation as a single dose, with or without pre-treatment with either alpha-adrenergic agonists (noradrenaline, phenylephrine) or a cholinergic antagonist (atropine). The effects were analyzed by morphometric, cytochemical and biophysical methods. When X-irradiated without drug pre-treatment, many serous epithelial cells of the intralobular convoluted ducts displayed morphologic evidence of irreversible radiation damage, in contrast to neighbouring mucous and other cells which were unaffected. The effect was maximal 96 h after irradiation. Serous cells from animals irradiated after pre-treatment with atropine showed much more wide-spread injury than those of animals exposed to X-irradiation only. In contrast , serous cells suffered considerably less damage if their secretory granules had been depleted 1 or 2 h before irradiation with either noradrenaline or phenylephrine. Other epithelial cells showed no modulation of their slight radioresponsiveness by these drugs. The observations were substantiated by morphometry of three cell types: (a) mucous cells, (b) non-granulated serous and intralobular striated duct cells, and (c) granulated serous cells. The findings suggest that the striking radiosensitivity of salivary gland serous epithelial cells is linked to their content of secretory granules. These granules are rich in heavy metals, as demonstrated cytochemically with the sulphide silver method (SSM). Using particle-induced X-ray emission ( PIXE ) spectroscopy, the principal metals were shown to be Zn, Mn and Fe. It is conceivable that membranes which enclose organelles rich in metals with the ability to form redox systems (e.g. Fe2+ in equilibrium Fe3+) show enhanced sensitivity to radiation damage due to the metal-catalyzed induction of lipid peroxidation by ionizing radiation. Disruption of secretory granules would be expected to release lytic enzymes into the cell sap, resulting in autolysis. This hypothesis is supported by the findings that atropine--which increases the number of granulated serous cells--enhances radiosensitivity, while noradrenaline and phenylephrine--which cause degranulation of serous cells--decrease radiosensitivity.

摘要

将雄性大鼠的下颌下腺单次暴露于50 Gy的X射线照射下,照射前使用或不使用α-肾上腺素能激动剂(去甲肾上腺素、苯肾上腺素)或胆碱能拮抗剂(阿托品)进行预处理。通过形态计量学、细胞化学和生物物理方法分析其效果。在未进行药物预处理的情况下进行X射线照射时,小叶内曲管的许多浆液上皮细胞显示出不可逆辐射损伤的形态学证据,而相邻的黏液细胞和其他细胞未受影响。这种效应在照射后96小时达到最大。用阿托品预处理后再进行照射的动物的浆液细胞,比仅接受X射线照射的动物的浆液细胞显示出更广泛的损伤。相反,如果在照射前1或2小时用去甲肾上腺素或苯肾上腺素使浆液细胞的分泌颗粒耗尽,那么这些浆液细胞受到的损伤会明显减少。其他上皮细胞对这些药物的轻微放射反应性没有调节作用。通过对三种细胞类型进行形态计量学分析证实了这些观察结果:(a)黏液细胞,(b)无颗粒浆液细胞和小叶内纹状管细胞,以及(c)有颗粒浆液细胞。研究结果表明,唾液腺浆液上皮细胞显著的放射敏感性与其分泌颗粒的含量有关。如用硫化银法(SSM)进行细胞化学证明,这些颗粒富含重金属。使用粒子诱导X射线发射(PIXE)光谱法,显示主要金属为锌、锰和铁。可以想象,包裹富含金属且能够形成氧化还原系统(如处于Fe3+平衡状态的Fe2+)的细胞器的膜,由于金属催化电离辐射诱导脂质过氧化,对辐射损伤表现出更高的敏感性。分泌颗粒的破坏预计会将裂解酶释放到细胞液中,导致自溶。这一假设得到以下研究结果的支持:阿托品(增加有颗粒浆液细胞的数量)会增强放射敏感性,而去甲肾上腺素和苯肾上腺素(导致浆液细胞脱颗粒)会降低放射敏感性。

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