Fractionated irradiation of salivary glands loss and protection of function

Abstract: Radiotherapy of malignancies in the head and neck often involves the major and minor salivary glands in the radiation field. Adverse effects, such as dry mouth symptoms, are common after such therapy. The aim of this thesis was to study longitudinal effects of fractionated irradiation to the head and neck on salivary gland function in man and in the rat and to test radioprotection from antioxidant vitamins (retinol, a-tocopherol and ^-carotene).A sharp decrease in parotid saliva flow rate was seen after one week of irradiation in cancer patients, but in some patients recovery was seen two months after completed treatment. Loss and recovery of salivary gland function were dependent on the total dose given. Irradiation with doses of >65 Gy to the parotid glands led to permanent loss of function in the majority of parotid glands, while recovery could be seen after irradiation with doses of <52 Gy. Concentrations of some proteins and electrolytes in saliva were increased during irradiation but no changes remained 18 months after radiotherapy. However, large inter-individual differences were seen.The irradiation effects observed in rats did not greatly differ from those seen in humans, but no recovery of salivary gland function was seen. On the one hand the impairments of saliva flow and composition w ere dose and time dependent, but on the other hand the response pattem differed between salivary components. Morphological alterations were not seen in the rat salivary' glands after tw'O or five weeks but 26 weeks after irradiation. No single model seems to be optimal for studying all parameters. Therefore, to study effects on salivary glands after irradiation the rat model must be adjusted to meet the questions addressed. Supplementation with vitamin A provided no radioprotection, whereas it w'as found that supplementation with a-tocopherol (3.4 mg/day) and ß-carotene (6 mg/day) during irradiation reduced the degree of inflammation and partly preserved salivary gland function. It did not, however, lead to morphometrically detectable differences in proportions of acinar or ductal cells or stroma.Keywords: Irradiation, salivary glands, saliva composition, antioxidants