Fractionated Irradiation and Late Changes in Rat Parotid Gland: Effects on the Number of Acinar Cells, Potassium Efflux, and Amylase Secretion

Abstract

Irradiation of head- and neck cancer commonly results in oral dryness and discomfort for the patients due to salivary gland damage. The exact mechanisms behind the inherent radiosensitivity of salivary glands remain to be elucidated. In the present study, we used different in vitro secretory models and quantitative morphological characterization of rat parotid gland following fractionated unilateral irradiation to one gland on a 5-day fraction schedule (Monday-Friday) with 6 MV photons (total dose 30, 35, 40 and 45 Gy) or a two-fractions regimens in 5 days (Monday and Friday) with total dose of 24 and 32 Gy. The contralateral shielded gland served as control, and parallel analyses of irradiated and control glands were performed 180 days following the last irradiation treatment. The relative noradrenaline stimulated electrolyte secretion (86rubidium tracer for potassium) was decreased in the irradiated compared with control glands. The noradrenaline-stimulated exocytotic amylase release was not significantly affected by irradiation, but the gland content of amylase was decreased dose-dependently. The quantitative morphological analysis revealed a dose-dependent decline in the number of acinar cells, whereas the other parenchymal cells (intercalated, striated- and excretory duct cells) were unaffected by the irradiation compared with control glands.

Short- and Long-term Effects of Irradiation on Laryngeal Mucosa of the Rat

“…In the submandibular and parotid glands, a larger quantity of connective tissue and a reduced number of acini have also been observed long after irradiation (8). The effect is dose dependent (8,25) and is more pronounced in the parotid gland, which contains only serous acini, which are more sensitive to irradiation than are mucous acini (8). As in the present study, the cells damaged by irradiation were replaced by connective tissue in those glands (8,19).…”

“…As observed previously (3,4), there was an increase in SP-, BN-and ENK-LI in the innervation of the subglottic glands 10 days after irradiation. A similar upregulation occurs in submandibular and parotid glands 10 days after irradiation (24,25). Thus, the change in granular ultrastructure occurs simultaneously with the change in neuropeptide pattern, implying a functional relationship.…”

Effects of Fractionated Irradiation on the Cytoskeleton and Basal Lamina in Parotid Glands: An Immunohistochemical Study

“…Neither the actin content nor the expression of cytokeratin 7 seemed to be affected, indicating a possibility of remaining secretory activity, which has been shown in secretory studies following adrenoceptor stimulation (4). In contrast, the amount of both these proteins increased in the lower part of these cells and also in duct cells.…”

“…The persistence of this expression after irradiation thus indicates remaining cytoskeletal structures which may be involved in the secretory processes. Evidence has been seen of an intact cellular response with amylase exocytosis on adrenergic stimuli 6 months after irradiation of up to 45 Gy (3,4). An increase in cytokeratin 7 and a lack of directional specialization after irradiation are puzzling from the point of differentiation.…”

“…These effects have been attributed to a direct acinar loss (1). Although DNA in theory is the sensitive cornerstone and target of the effects of irradiation, other cell and tissue constituents such as cell membrane (2)(3)(4), vascular effects (5, 6), enzyme-containing secretory granules (7,8) have been suggested as primary targets for the noxious radiation. It has also been shown that fractionated irradiation causes early effects on membrane-coupled secretory events, i.e.…”