PMID: 7545909Feb 1, 1994Paper

Analysis of K-ras, p53 and c-raf-1 mutations in beryllium-induced rat lung tumors

Carcinogenesis
C Nickell-BradySteven A Belinsky

Abstract

Beryllium (Be) metal and several of its analogues have been shown to be carcinogenic in rats. In addition, workers employed at Be processing plants have been shown to have a slight excess of lung cancer. In this study, a single inhalation exposure to Be metal produced a 64% incidence of lung tumors in the F344/N rat. The most frequent tumor type observed was adenocarcinoma. These Be metal-induced lung carcinomas were examined for genetic alterations in the K-ras, p53, and c-raf-1 genes. DNA isolated from lung neoplasms was analyzed by PCR amplification and direct DNA sequence analysis, immunohistochemical analysis and Southern blot analysis. No K-ras codon 12, 13 or 61 mutations were detected in 24 lung tumors by direct sequencing. Using a more sensitive K-ras codon 12 mutation selection assay, K-ras codon 12 GGT-GTT transversions were detected in two of 12 adenocarcinomas. These results suggest that activation of the K-ras protooncogene is both a rare and late event, possibly stemming from genomic instability during the progression of some Be-induced rat adenocarcinomas of the lung. No mutant p53 nuclear immunoreactivity was observed in any Be-induced tumor. Because immunohistochemical analysis of the p53 protein only detects ...Continue Reading

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