Genetics of susceptibility of rats to trigeminal schwannomas induced by neonatal administration of N-ethyl-N-nitrosourea.

A genetic analysis was done on the induction of trigeminal schwannomas by N-ethyl-N-nitrosourea [(ENU) CAS: 759-73-9] in susceptible LE rats, resistant WF rats, and their F1, F2, and reciprocal backcross hybrids. Both sexes of all strains were given a neonatal sc injection of 40 mg ENU/kg body weight and were sacrificed at 6 months after treatment. Many neurogenic tumors were induced in the central nervous system of all strains of rats. However, the incidence of trigeminal schwannomas in LE rats was 93% in males and 86% in females, whereas in WF rats the incidence was 24% in males and 20% in females. F1 and F2 hybrids showed an intermediate susceptibility (62 and 82% in F1 males, 79 and 86% in F2 males, 26 and 38% in F1 females, and 65 and 77% in F2 females). The incidence in hybrids backcrossed to LE was high (90 and 100% in males and 77 and 83% in females), and the incidence in hybrids backcrossed to WF was low (35 and 38% in males and 11 and 7% in females). The findings suggest that susceptibility to the induction of trigeminal schwannomas by ENU does not result from the expression of genes that are simple dominant or recessive genes. A genetic model involving three independently segregating loci may explain the experimental results. In all strains of rats, particularly the F1 hybrids, males were more susceptible than females to the induction of trigeminal schwannomas by ENU.