Bartel-Friedrich S, Friedrich R E, Lautenschläger C, Holzhausen H J
Department of Otorhinolaryngology, University Hospital, Martin Luther University Halle-Wittenberg, Magdeburger Str. 12, 06097 Halle a.d.S., Germany.
Anticancer Res. 2000 Nov-Dec;20(6D):5221-8.
The extent of radiogenic salivary tissue damage (direct cell damage, reactive cell infiltration, increasing fibrosis) depends on the radiation dose (RD), the fractionation (FN) and the localisation of the salivary gland (SG) in the radiation field (RF). Because the histological damage is characterized by cellular and structural alterations and because extracellular matrix proteins, for example laminin (LA), are among the main components of the basement membrane (BM), which is considered to possess cell- and tissue structure-regulating functions, we set out to describe radiogenic BM changes.
In 124 rat mandibular SG we investigated HE-stained sections and the LA staining profile (LASP) dependent on age [1 year (y) vs. 1 1/2 y], on FN [2 Gy/day up to a total dosage of 20/40/60 Gy (X-rays)], on RF [(left head and neck area); inside (left-sided SG) vs. outside (right-sided SG) RF] and on the latency of irradiation (1/2 y vs. 1 y) using immunohistochemical methods and multivariate analysis.
The immunoreactivity of the polyclonal antibody in the rat did not differ from the LASP in humans. LA was detected at variable levels in the glandular tissue, in vascular walls (without staining in the adventitia) and in nerve tissue (NT). No reaction was found in the capsule and the trabecula. In irradiated SG most tissue structures, including the vascular wall and NT, showed significantly stronger staining (both increased intensity and more extended expression). With increasing RD from 20 Gy to 60 Gy we found an increasing staining reaction. In addition, conglomerated LA depots were noted, especially in ares of disturbed or former acini of glands exposed to 60 Gy. The LASP up to 20 Gy was non-uniform and did not differ significantly from that in controls. A remarkable finding was the similar dose-dependent increase in staining reaction on both sides in several tissues of irradiated animals. Predominantly, however, we found considerably greater increases in staining in directly exposed glands than in out-of-field glands. Age and time since irradiation had no significant effect on staining.
The BM constituent LA showed dose-dependent increases in expression--analogous to positively dose-dependent increasing SG tissue damage--which could contribute to disturbed cell-matrix interaction and SG radiation damage. Several parenchymal structures may be more sensitive to possible scattered radiation.
放射性唾液腺组织损伤的程度（直接细胞损伤、反应性细胞浸润、纤维化加重）取决于辐射剂量（RD）、分割方式（FN）以及唾液腺（SG）在辐射野（RF）中的位置。由于组织学损伤以细胞和结构改变为特征，且细胞外基质蛋白，如层粘连蛋白（LA），是基底膜（BM）的主要成分之一，而基底膜被认为具有调节细胞和组织结构的功能，因此我们着手描述放射性基底膜的变化。
我们对124只大鼠的下颌唾液腺进行研究，采用免疫组化方法和多变量分析，观察苏木精 - 伊红（HE）染色切片以及取决于年龄[1岁（y）与1.5岁]、分割方式[每天2 Gy，总剂量达20/40/60 Gy（X射线）]、辐射野[（左头颈部区域）；辐射野内（左侧唾液腺）与辐射野外（右侧唾液腺）]以及照射潜伏期（半年与1年）的LA染色谱（LASP）。
大鼠中多克隆抗体的免疫反应性与人类的LASP无差异。在腺组织、血管壁（外膜无染色）和神经组织（NT）中检测到不同水平的LA。在被膜和小梁中未发现反应。在受照射的唾液腺中，大多数组织结构，包括血管壁和NT，染色明显增强（强度增加且表达范围扩大）。随着辐射剂量从20 Gy增加到60 Gy，我们发现染色反应增强。此外，观察到LA聚集库，尤其是在接受60 Gy照射的腺体的紊乱或先前腺泡区域。辐射剂量达20 Gy时LASP不均匀，与对照组无显著差异。一个显著发现是，在受照射动物的多个组织中，两侧染色反应均有类似的剂量依赖性增加。然而，主要的是，我们发现直接暴露的腺体中的染色增加明显大于野外腺体。年龄和照射后的时间对染色无显著影响。
基底膜成分LA的表达呈剂量依赖性增加——类似于唾液腺组织损伤的正剂量依赖性增加——这可能导致细胞 - 基质相互作用紊乱和唾液腺辐射损伤。一些实质结构可能对可能的散射辐射更敏感。
