Radiation induced cell loss in rat submandibular gland and its relation to gland function

PURPOSE: To understand early and late radiation-induced loss of function of the submandibular gland, changes in cell number were documented and correlated with data on gland function. Modulation of the radiation effect by sialogogues was used to investigate possible mechanisms of action. MATERIALS AND METHODS: Rats were irradiated with a single dose of 15 Gy of X-rays after pre-treatment with either saline, the muscarinic receptor agonists methacholine or pilocarpine, the adrenergic receptor agonist phenylephrine or methacholine plus phenylephrine. Before and 1-240 days after irradiation, submandibular saliva flow rate was measured. At the same time points and from comparable animals submandibular glands were carefully extirpated, weighed and prepared for light microscopic examination. RESULTS: Soon after irradiation (<30 days) no significant loss of cells was observed, whereas the gland function was severely compromised. Sialogogue pre-treatment attenuated the radiation-induced loss of gland function. At later intervals a considerable loss of acinar cells and to a lesser extent loss of granular convoluted tubule cells were observed. Gland function subsequently declined slowly. Pre-treatment with sialogogues gave transient protection against cell loss and loss of gland function. CONCLUSIONS: The lack of cell loss observed soon after irradiation indicates that the observed reduction in gland function was caused by a compromised functioning of the acini. The later loss of cells is probably due to death of cells that normally proliferate, leading to a further reduced secretory capacity. Protection of gland morphology and function by sialogogues at later times must therefore involve resistance of progenitor cells to radiation-induced cell death.