p53, erbB-2 and K-ras gene alterations are rare in spontaneous and plutonium-239-induced canine lung neoplasia

Journal Article · Thu Feb 01 04:00:00 EST 1996 · Radiation Research

DOI:https://doi.org/10.2307/3579173· OSTI ID:387316

Tierney, L A; Hahn, F F; Lechner, J F ^[1]

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1. Inhalation Toxicology Research Inst., Albuquerque, NM (United States)

Inhalation of high-linear energy transfer radiation in the form of radon progeny is a suspected cause of human lung cancer. To gain insight into the types of genetic derangements caused by this type of radiation, lung tumors from beagle dogs exposed to {sup 239}PuO{sub 2} and those arising in animals with no known carcinogen exposure were examined for evidence of aberrations in genes known to be altered in lung tumors. Altered expression of the p53 tumor suppressor gene and proto-oncogene erbB-2 proteins (p185{sup erbB2}) was evaluated by immunohistochemical analysis of 117 tumors representing different histological types in exposed (n = 80) and unexposed (n = 37) animals. Twenty-eight tumors were analyzed for K-ras proto-oncogene mutations by polymerase chain reaction amplification and direct sequencing. Fourteen percent (16/116) of all lung neoplasms showed elevated nuclear accumulation of p53 protein. Regardless of exposure history, adenosquamous and squamous cell cancers comprised 94% of all tumors with p53 abnormalities. Eighteen percent (21/117) of all tumors had evidence of erbB-2 protein overexpression. K-ras mutations were not detected in codons 12, 13 or 61 of tumors from unexposed (n = 9) or plutonium-exposed dogs (n = 19). These data indicate that p53 and K-ras gene abnormalities as a result of missense mutation are infrequent events in spontaneous and {sup 239}PuO{sub 2}-induced lung neoplasia in this colony of beagle dogs. Alternative mechanisms of gene alteration may be involved in canine pulmonary carcinogenesis. 45 refs., 3 figs., 2 tabs.

• Sponsoring Organization: USDOE
• DOE Contract Number: AC04-76EV01013
• OSTI ID: 387316
• Journal Information: Radiation Research, Journal Name: Radiation Research Journal Issue: 2 Vol. 145; ISSN RAREAE; ISSN 0033-7587
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
ALPHA PARTICLES
BEAGLES
CARCINOMAS
DNA SEQUENCING
GENE MUTATIONS
GENE REGULATION
GENES
GENETIC RADIATION EFFECTS
INHALATION
LET
MUTATION FREQUENCY
ONCOGENES
PLUTONIUM 239
POLYMERASE CHAIN REACTION
PROTEINS
RADIATION DOSES
RADIOACTIVE AEROSOLS
RADON