Activated neu oncogene sequences in primary tumors of the peripheral nervous system induced in rats by transplacental exposure to ethylnitrosourea

Journal Article · Tue Sep 01 00:00:00 EDT 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.17.6317· OSTI ID:5230737

Perantoni, A O; Rice, J M; Reed, C D; Watatani, M; Wenk, M L

Neurogenic tumors were selectively induced in high incidence in F344 rats by a single transplacental exposure to the direct-acting alkylating agent N-ethyl-N-nitrosourea (EtNU). The authors prepared DNA for transfection of NIH 3T3 cells from primary glial tumors of the brain and form schwannomas of the cranial and spinal nerves that developed in the transplacentally exposed offspring between 20 and 40 weeks after birth. DNA preparations from 6 of 13 schwannomas, but not from normal liver, kidney, or intestine of tumor-bearing rats, transformed NIH 3T3 cells. NIH 3T3 clones transformed by schwannoma DNA contained rat repetitive DNA sequences, and all isolates contained rat neu oncogene sequences. A point mutation in the transmembrane region of the putative protein product of neu was identified in all six transformants and in the primary tumors from which they were derived as well as in 5 of 6 schwannomas tested that did not transform NIH 3T3 cells. Of 59 gliomas, only one yielded transforming DNA, and an activated N-ras oncogen was identified. The normal cellular neu sequence for the transmembrane region, but not the mutated sequence, was identified in DNA from all 11 gliomas surveyed by oligonucleotide hybridization. Activation of the neu oncogene, originally identified in cultured cell lines derived from EtNU-induced neurogenic tumors appears specifically associated with tumors of the peripheral nervous system in the F344 inbred strain.

• Research Organization: National Cancer Institute, Frederick, MD (USA)
• OSTI ID: 5230737
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:17
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
NITROSOUREAS
GENETIC EFFECTS
PRENATAL EXPOSURE
ONCOGENES
CHEMICAL ACTIVATION
DNA SEQUENCING
CARCINOGENESIS
FIBROBLASTS
GENE MUTATIONS
GLIOMAS
HYBRIDIZATION
MICE
NERVES
OLIGONUCLEOTIDES
PHOSPHORUS 32
RATS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DISEASES
GENES
ISOTOPES
LIGHT NUCLEI
MAMMALS
MUTATIONS
NEOPLASMS
NERVOUS SYSTEM
NITROSO COMPOUNDS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATHOGENESIS
PHOSPHORUS ISOTOPES
RADIOISOTOPES
RODENTS
SOMATIC CELLS
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology