IRRADIATION-INDUCED DAMAGE TO THE SALIVARY-GLANDS - THE ROLE OF REDOX-ACTIVE IRON AND COPPER

The mechanism of irradiation-induced hypofunction of the salivary glan ds is a process that is not fully understood. Here we examine the hypo thesis that intracellular and redox-active ions of iron and copper, wh ich are associated with the secretion granules, play a catalytic role in the irradiation-induced damage. Rats were subjected to head and nec k irradiation (15 Gy X rays) and allowed to recover for 2 months. The function of the parotid and submandibular glands was then determined b y pilocarpine-stimulated salivary secretion. A 45% decrease in the fun ction of both glands was obtained when compared to nonirradiated contr ols. Treatment prior to irradiation (90 min) with cyclocytidine (200 m g/kg) led to a massive degranulation of the parotid gland and yielded nearly complete protection from radiation-induced damage. In contrast, pilocarpine stimulation prior to irradiation led to a marginal degran ulation of the parotid gland and yielded only 13% protection. Neither agent caused degranulation of the submandibular gland mucous cells or yielded functional protection of this gland. Treatment with both agent s yielded a marked increase in iron, copper and manganese levels in th e parotid gland saliva. An analogous marked increase in the redox acti vity of iron and copper ions was recorded for the parotid saliva stimu lated by pilocarpine and cyclocytidine. Pilocarpine-stimulated submand ibular gland saliva contained metal levels similar to those of the par otid gland saliva. However, no redox activity and no increase in metal mobilization could be demonstrated in the submandibular gland saliva stimulated by both agents. The correlation between the patterns of gla nd degranulation, mobilization of redoxactive metals and the protectio n of gland function, for both parotid and submandibular glands, focuse s attention on the catalytic roles played by transition metal ions in promoting free radical reactions, which likely participate in the proc ess of injury to the tissue. (C) 1997 by Radiation Research Society.