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

The occurrence of trigeminal nerve tumors (TNTs) induced byneonatal administration of N-ethyl-N-nitrosourea (ENU) in WF? LE F₁ (F₁ rats was studied with special reference to sex difference,effect of gonadectomy and estradiol (E₂) administration. Experimentalgroups 1–6 were treated with 40 mg ENU/kg of body weightneonatally. They consisted of male, female, castrated male,ovariectomized female, E₂ pellet (0.1 mg, s.c.) supplementedand gonadectomized male and female rats respectively. Rats ofgroups 7–12 served as the respective controls withoutENU. All the rats were killed at 8 months of age. Levels ofserum 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 < 0.05) and did not change by castrationin males (91%) but increased in ovariectomized female rats (74%,P < 0.05). Administration of E₂ followed by gonadectomy inhibitedthe occurrence of TNTs in male rats (59%) but not in femalerats (60%). No TNT was observed in any control groups. Kidneytumors were the second most frequent tumors next to nervoussystem tumors in the present experiment. The incidence of kidneytumors was much higher in females (38%) than in males (4%, P< 0.05) and decreased by ovariectomy, whereas it increasedin male rats by E₂ administration. ER levels of TNTs and trigeminalnerve tissue were < 1 fmol/mg protein. These results suggestthat in rats treated with ENU neonatally, E₂ has an inhibitoryeffect on the induction of TNTs but may not be regulated throughER. E₂ also shows a promoting effect on kidney tumorigenesis.