Increase in mast cells and hyaluronic acid correlates to radiation-induced damage and loss of serous acinar cells in salivary glands: the parotid and submandibular glands differ in radiation sensitivity

Abstract

Summary The detailed mechanisms which can explain the inherent radiosensitivity of salivary glands remain to be elucidated. Although DNA is the most plausible critical target for the lethal effects of irradiation, interactions with other constituents, such as cell membrane and neuropeptides, have been suggested to cause important physiological changes. Moreover, mast cells seem to be closely linked to radiation-induced pneumonitis. Therefore, in the present study the effects of fractionated irradiation on salivary glands have been assessed with special regard to the appearance of mast cells and its correlation with damage to gland parenchyma. Sprague-Dawley strain rats were unilaterally irradiated to the head and neck with the salivary glands within the radiation field. Although the detailed mechanisms by which radiation induces damage in biological tissues are not fully understood, it is generally accepted that generation of free radicals is of major importance. DNA is the most likely target for the lethal effects of these irradiation induced free radicals, however it is plausible that other compartments, i.e. non-genetic macromolecules, such as proteins and carbohydrates, can be significantly affected with vital alterations in the functional integrity of the certain biological tissues (Creasy, 1960;Desai et al., 1964;Sutherland et al., 1967;Alper, 1977;El-Mofty et al., 1981;Franzen et al., 1991;1993). In addition, changes caused by external factors and in the surrounding tissues can play an important role in modifying the final detectable and evaluable reaction, which indeed has recently been proposed, e.g. ongoing smoking depressed pneumonitis caused by irradiation in humans (Franzen et al., 1989;Bjermer et al., 1990; as well as in experimental animals . Moreover, sublethal damage following fractionated irradiation seems to cause alterations in cell membrane function and in physiological parameters (Reade & Steidler, 1985; Stephens et al., 1986a,b;Franzen et al., 1991). Most recently, it was also demonstrated that irradiation enhances the expression of important neutopeptides/growth factors, at least in salivary glands (Forsgren et al., 1992;Franzen et al., 1993). Furthermore, parotid acinar cell death following irradiation has been described as an interphase death (Stephens et al., 1986a,b;Franzen et al., 1991).The remarkable sensitivity of salivary gland acinar cells compared with other glands to radiation is a unique radiobiological phenomenon (Shannon et al., 1978;Mira et al., 1982;Abok et al., 1984;Junglee et al., 1986;Franzen et al., 1991). Other well-differentiated gland cells are known to be more or less radioresistant (Rubin & Casarett, 1972). The exact mechanism which explains this sensitivity is not entirely understood. Since mast cells have been proposed to interact in a substantial manner with the development of radiationinduced pneumonitis and pulmonary fibrosis (Franzen et al., 1989;Bjermer et al., 1990; Nilsson et al., 1990a,b; we found it of interest to evaluate the correlation of connecti...

Rat Salivary Gland Function after Fractionated Irradiation

“…The same authors also reported recently that a single dose of 2.5 Gy to the rat significantly reduced parotid salivary flow rate 12 months after irradiation (32). A more pronounced radiosensitivity of the parotid than the submandibular glands has also been suggested from morphological evaluations (33). The concentration of potassium in saliva, but not the total output, increased with time and irradiation doses up to 6 Gy x 5.…”

Ultrasound GLCM texture analysis of radiation‐induced parotid‐gland injury in head‐and‐neck cancer radiotherapy: An in vivo study of late toxicity

“…Histological studies have reported that normal parotid glands are filled with homogenous serous acinar cells that contain densely packed translucent secretory granules. 39,40 Those densely packed cells and granules provide uniform and highly reflective interfaces for the ultrasound beam, 41 producing for the homogeneous and hyperechoic appearance of the normal parotid glands. After irradiation, many acini are lost with the remaining acini appearing larger than normal and more disorganized.…”

Oral Sequelae of Head and Neck Radiotherapy

“…This was confirmed in an in vitro study showing that muscarinic receptor-induced calcium mobilization and protein kinase C activation were affected ). The late effects of radiation on the parotid and submandibular glands have been studied less extensively, and have been reported as a dose-dependent further decline in function (Nagler et al, 1998;) and loss of acinar cells (Henricksson et al, 1994;O'Connell et al, 1999). Unfortunately, in the latter studies the whole or half of the head including the glands was irradiated.…”

“…Within three days after irradiation with a single dose of 15 Gy of x-rays, a decrease in salivary flow of nearly 50% can be observed (Vissink et al, 1990;Peter et al, 1995;Coppes et al, 1997aCoppes et al, ,b, 2001Zeilstra et al, 2000). Lack of obvious quantitative morphological alterations (Franzén et al, 1991;Henricksson et al, 1994;Zeilstra et al, 2000;, a rather quick recovery of the morphological changes if they occur (Vissink et al, 1991), and a lack of increase in apoptotic cells early after radiotherapy (Paardekooper et al, 1998) point to the presence of altered cell membranes (Sodicoff et al, 1974;El Mofty and Kahn, 1981;Vissink et al, 1992) and/or a disturbed intracellular signaling (Vissink et al, 1991;Coppes et al, 1997b) as the cause of the early effect of radiation on the parotid gland. This was confirmed in an in vitro study showing that muscarinic receptor-induced calcium mobilization and protein kinase C activation were affected ).…”