neu mutation in schwannomas induced transplacentally in Syrian golden hamsters by N-nitrosoethylurea: high incidence but low allelic representation

Peripheral nerve tumors (PNT) and melanomas induced transplacentally on day 14 of gestation in Syrian golden hamsters by N-nitrosoethylurea were analy zed for activated oncogenes by the NIH 3T3 transfection assay, and for muta tions in the neu oncogene by direct sequencing, allele-specific oligonucleo tide hybridization, MnlI restriction-fragment-length polymorphism, single-s trand conformation polymorphism, and mismatch amplification mutation assays . All (67/67) of the PNT, but none of the melanomas, contained a somatic mi ssense T --> A transversion within the neu oncogene transmembrane domain at a site corresponding to that which also occurs in rat schwannomas transpla centally induced by N-nitrosoethylurea. In only 2 of the 67 individual hams ter PNT did the majority of tumor cells appear to carry the mutant neu alle le, in contrast to comparable rat schwannomas in which it overwhelmingly pr edominates. The low fraction of hamster tumor cells carrying the mutation w as stable through multiple transplantation passages. In the hamster, as in the rat, specific point-mutational activation of the neu oncogene thus cons titutes the major pathway for induction of PNT by transplacental exposure t o am alkylating agent, but the low allelic representation of mutant neu in hamster PNT suggests a significant difference in mechanism by which the mut ant oncogene acts in this species.