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

Abstract

Peripheral nerve tumors (PNT) and melanomas induced transplacentally on day 14 of gestation in Syrian golden hamsters by N-nitrosoethylurea were analyzed for activated oncogenes by the NIH 3T3 transfection assay, and for mutations in the neu oncogene by direct sequencing, allele-specific oligonucleotide hybridization, MnlI restriction-fragment-length polymorphism, single-strand conformation polymorphism, and mismatch amplification mutation assays. All (67/67) of the PNT, but none of the melanomas, contained a somatic missense T --> A transversion within the neu oncogene transmembrane domain at a site corresponding to that which also occurs in rat schwannomas transplacentally induced by N-nitrosoethylurea. In only 2 of the 67 individual hamster PNT did the majority of tumor cells appear to carry the mutant neu allele, in contrast to comparable rat schwannomas in which it overwhelmingly predominates. The low fraction of hamster tumor cells carrying the mutation was stable through multiple transplantation passages. In the hamster, as in the rat, specific point-mutational activation of the neu oncogene thus constitutes the major pathway for induction of PNT by transplacental exposure to an alkylating agent, but the low allelic representation of mutant neu in hamster PNT suggests a significant difference in mechanism by which the mutant oncogene acts in this species.

• Authors: G S Buzard, T Enomoto, T Hongyo, A O Perantoni, B A Diwan, D E Devor, C D Reed, L F Dove, J M Rice
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 125 Issue 10 Pg. 529-40 (Oct 1999) ISSN: 0171-5216 [Print] Germany
• PMID: 10473865 (Publication Type: Journal Article)

Chemical References

• Alkylating Agents
• DNA, Neoplasm
• Mutagens
• Receptor, ErbB-2
• Ethylnitrosourea

Topics

• Alkylating Agents (adverse effects)
• Alleles
• Animals
• Blotting, Southern
• Cricetinae
• DNA, Neoplasm (analysis)
• Ethylnitrosourea (adverse effects)
• Fetal Diseases (genetics)
• Genes, erbB-2 (drug effects, genetics)
• Incidence
• Melanoma (chemically induced, genetics)
• Mesocricetus
• Mutagens (adverse effects)
• Mutation
• Neurilemmoma (chemically induced, genetics)
• Peripheral Nervous System Neoplasms (chemically induced, genetics)
• Placenta
• Polymerase Chain Reaction
• Polymorphism, Restriction Fragment Length
• Receptor, ErbB-2 (genetics)
• Transfection