The enigmatic mechanism of irradiation-induced damage to the major salivary glands
The enigmatic mechanism of irradiation-induced damage to the major salivary glands
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DOI：
10.1034/j.1601-0825.2002.02838.x
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发表时间：
2002-05-01
期刊：
影响因子：
3.8
通讯作者：
Nagler, RM
中科院分区：
文献类型：
--
作者：
Nagler, RM
放疗是头颈部恶性肿瘤的一种中心治疗方式。其主要且最具破坏性的副作用是对主要唾液腺的诱导损伤。这篇文章的目的是提出一个全面的解释，这种损害的根本机制，这一直被认为是在整个90年以来，它是在1911年首次描述的谜。提出的机制是基于大量的文献关于这个谜在大鼠唾液腺。根据这一机制，辐射导致亚致死性DNA损伤，其表现为并在延迟阶段变得致命。因此，当腺泡祖细胞经历需要实质细胞补充的生殖阶段时，它们死亡。导致这种延迟生殖细胞死亡的有害物质似乎是高度氧化还原活性的过渡金属离子，如铁和铜。这些金属离子，似乎与分泌颗粒，不一定包含在颗粒如前所述，而是可能位于更接近DNA的网站。
Irradiation is a central treatment modality administered for head and neck malignancies. Its major and most devastating side-effect is an induced damage to the major salivary glands. This article aims at suggesting a comprehensive explanation for the underlying mechanism of this damage, which has been considered as enigmatic throughout the 90 years since it was first described in 1911. The mechanism suggested is based on the considerable literature concerning this enigma in rat salivary glands. According to this proposed mechanism, the irradiation results in a sublethal DNA damage, which manifests and becomes lethal at a delayed phase. Thus, when the acinar progenitor cells are going through a reproductive phase when parenchylmal replenishment is required, they die. The injurious agents, which result in this delayed reproductive cell death, appear to be highly redox-active transition metal ions, such as iron and copper. These metal ions, which seem to be associated with secretion granules, are not necessarily contained within the granules as previously suggested, but rather are probably located at sites more proximal to the DNA.