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K-ras mutations in 239PuO2 canine lung neoplasms.
S M Griffey1, S A Kraegel, R E Weller
1Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis 95616, USA.
Cancer Letters
|July 9, 1999
Summary
K-ras mutations were found in 8% of plutonium-exposed beagle lung tumors, a higher rate than previously seen in canine plutonium-induced cancers but lower than spontaneous lung cancers in dogs and humans.
Area of Science:
- Radiobiology
- Oncology
- Molecular Biology
Background:
- Plutonium dioxide (239PuO2) inhalation exposure is a known risk factor for lung cancer.
- Investigating genetic alterations in lung tumors can elucidate cancer development mechanisms.
Purpose of the Study:
- To identify mutations in the K-ras gene in lung tumors from beagle dogs exposed to 239PuO2.
- To compare the frequency of K-ras mutations in plutonium-induced lung tumors to other canine and human lung cancers.
Main Methods:
- Single-strand conformational polymorphism (SSCP) analysis and direct sequencing were employed.
- Tumor tissues from 25 beagle dogs with documented 239PuO2 inhalation exposure and subsequent lung tumors were analyzed.
- Exon 1 of the K-ras gene was specifically examined for mutations.
Main Results:
- Mutations in the K-ras gene were detected in 2 out of 25 (8%) plutonium-induced lung tumors.
- Both identified mutations were GGT to GAT transitions at codon 12.
- The mutation rate (8%) was higher than in previous studies of canine plutonium-induced lung tumors (0%) but lower than in spontaneous canine lung cancer (16%) and human non-small cell lung cancer (13-36%).
Conclusions:
- The K-ras gene is a potential target for mutations in plutonium-induced canine lung cancer.
- The observed mutation frequency suggests a role for K-ras in the pathogenesis of radiation-induced lung tumors.
- Further research is warranted to understand the full spectrum of genetic changes in plutonium-induced lung cancers.