The enigmatic mechanism of irradiation-induced damage to the major salivary glands.
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 parenchymal 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.
Nagler
R M
RM
Department of Oral and Maxillofacial Surgery, Rambam Medical Center, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa. nagler@tx.technion.ac.il
D000818:Animals; D016923:Cell Death; D003300:Copper / Q000528:radiation effects; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D004195:Disease Models, Animal; D006801:Humans; D007501:Iron / Q000528:radiation effects; D008938:Mitosis / Q000528:radiation effects; D010084:Oxidation-Reduction; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology*; D011878:Radiotherapy / Q000009:adverse effects; D051381:Rats; D012466:Salivary Gland Diseases / Q000209:etiology*; D012469:Salivary Glands / Q000378:metabolism / Q000528:radiation effects*; D012636:Secretory Rate / Q000528:radiation effects; D022142:Secretory Vesicles / Q000528:radiation effects; D013234:Stem Cells / Q000528:radiation effects
D003300:Copper; D004247:DNA; D007501:Iron