The molecular progression of plutonium-239-induced rat lung carcinogenesis: Ki-ras expression and activation

Journal Article · Tue Jan 01 04:00:00 EST 1991 · Mol. Carcinog; (USA)

DOI:https://doi.org/10.1002/mc.2940040108· OSTI ID:5799713

Stegelmeier, B L; Gillett, N A; Rebar, A H; Kelly, G ^[1]

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1. Inhalation Toxicology Research Institute, Albuquerque, NM (USA)

Specific, transforming point mutations of ras and alterations in ras expression have been associated with many neoplastic processes, and their presence may be pivotal in neoplastic transformation. Our objective were to evaluate the molecular and genetic alterations of Ki-ras in preneoplastic foci and neoplasms in the lungs of rats that inhaled {sup 239}PuO{sub 2} aerosols. Histologically classified pulmonary lesions were evaluated by in vitro nucleic acid amplification, oligonucleotide hybridization, and direct nucleic acid sequencing for activating Ki-ras point mutations. We evaluated ras expression in similar lesions using immunohistochemistry and in situ hybridization. Specific Ki-ras point mutations were present in 46% of the radiation-induced malignant neoplasms. Spontaneous pulmonary neoplasms, which are rare in rats, had similar activating mutations and frequencies (40%). We found similar mutation frequencies in radiation-induced adenomas and foci of alveolar epithelial hyperplasia. No mutations were identified in normal lung tissue. Ras expression in hyperplastic lesions and neoplasms was similar to that observed in normal pulmonary epithelia. These findings suggest that Ki-ras activation, not alterations in expression, is an early lesion associated with many radiation-induced, proliferative pulmonary lesions and that this molecular alteration may be an important component of both radiation-induced and spontaneous pulmonary carcinogenesis in the rat.

• OSTI ID: 5799713
• Journal Information: Mol. Carcinog; (USA), Journal Name: Mol. Carcinog; (USA) Vol. 4:1; ISSN 0899-1987; ISSN XY971
• Country of Publication: United States
• Language: English

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACTINIDE ISOTOPES
ACTINIDE NUCLEI
ALPHA DECAY RADIOISOTOPES
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RADIOINDUCTION
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RESPIRATORY SYSTEM
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