Effects of sex difference, gonadectomy and estradiol on N-ethyl-N-nitrosourea-induced trigeminal nerve tumors in rats.

Abstract

The occurrence of trigeminal nerve tumors (TNTs) induced by neonatal administration of N-ethyl-N-nitrosourea (ENU) in WF x LE F1 (F1) rats was studied with special reference to sex difference, effect of gonadectomy and estradiol (E2) administration. Experimental groups 1-6 were treated with 40 mg ENU/kg of body weight neonatally. They consisted of male, female, castrated male, ovariectomized female, E2 pellet (0.1 mg, s.c.) supplemented and gonadectomized male and female rats respectively. Rats of groups 7-12 served as the respective controls without ENU. All the rats were killed at 8 months of age. Levels of serum E2 and E2 receptor (ER) of the TNTs were also examined. It was noted that the incidence of TNT was higher in males (79%) than in females (48%, P less than 0.05) and did not change by castration in males (91%) but increased in ovariectomized female rats (74%, P less than 0.05). Administration of E2 followed by gonadectomy inhibited the occurrence of TNTs in male rats (59%) but not in female rats (60%). No TNT was observed in any control groups. Kidney tumors were the second most frequent tumors next to nervous system tumors in the present experiment. The incidence of kidney tumors was much higher in females (38%) than in males (4%, P less than 0.05) and decreased by ovariectomy, whereas it increased in male rats by E2 administration. ER levels of TNTs and trigeminal nerve tissue were less than 1 fmol/mg protein. These results suggest that in rats treated with ENU neonatally, E2 has an inhibitory effect on the induction of TNTs but may not be regulated through ER. E2 also shows a promoting effect on kidney tumorigenesis.