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 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.
Buzard
G S
GS
Carcinogenesis Study Section, Intramural Research Support Program, SAIC Frederick, Bldg 538, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA. buzardg@mail.ncifcrf.gov
Enomoto
T
T
Hongyo
T
T
Perantoni
A O
AO
Diwan
B A
BA
Devor
D E
DE
Reed
C D
CD
Dove
L F
LF
Rice
J M
JM
D000477:Alkylating Agents / Q000009:adverse effects*; D000483:Alleles; D000818:Animals; D015139:Blotting, Southern; D006224:Cricetinae; D004273:DNA, Neoplasm / Q000032:analysis; D005038:Ethylnitrosourea / Q000009:adverse effects*; D005315:Fetal Diseases / Q000235:genetics*; D018734:Genes, erbB-2 / Q000187:drug effects / Q000235:genetics*; D015994:Incidence; D008545:Melanoma / Q000139:chemically induced / Q000235:genetics*; D008647:Mesocricetus; D009153:Mutagens / Q000009:adverse effects*; D009154:Mutation; D009442:Neurilemmoma / Q000139:chemically induced / Q000235:genetics*; D010524:Peripheral Nervous System Neoplasms / Q000139:chemically induced / Q000235:genetics*; D010920:Placenta; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D014162:Transfection
D000477:Alkylating Agents; D004273:DNA, Neoplasm; D005038:Ethylnitrosourea; D009153:Mutagens; D018719:Erb-b2 Receptor Tyrosine Kinases