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Environ Mol Mutagen. 2002;40(1):36-40.

Mutation analysis of K-ras-2 in liver angiosarcoma and adjacent nonneoplastic liver tissue from patients occupationally exposed to vinyl chloride.

Author information

1
Institute of Occupational Medicine, University of Hannover, Germany.

Abstract

Vinyl chloride (VC) is a potent liver carcinogen that induces angiosarcomas in humans and animals. Recent evidence shows that liver tumors from patients with VC exposure may have a specific K-ras mutation pattern. This study was performed to determine the status of K-ras-2 in liver angiosarcomas (LAS) from workers occupationally exposed to VC. We examined the presence of K-ras-2 mutations in 15 LAS from patients with known exposure to VC (median exposure: 8,260 ppm [range 3,900- 21,000 ppm]]. In all cases, other risk factors for the development of LAS were excluded. Direct DNA sequencing after microdissection of the tumor cells was used for the analysis. Heterozygous mutations of K-ras-2 were detected in 8/15 LAS (53%). Five patients (33%) had a mutation of codon 12 and three of codon 13 (20%). The most common changes were G-->A transitions in five LAS which lead to the substitution of aspartic acid for glycine in the resulting p21 protein. In two patients (13%), mutations of the K-ras-2 gene were identified in the adjacent nonneoplastic liver tissue. These data indicate that VC induces a high frequency of G-->A transitions in human LAS. This mutation pattern is likely a consequence of VC-DNA-adduct formation.

PMID:
12211074
DOI:
10.1002/em.10084
[Indexed for MEDLINE]

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