Ras gene mutations in vinyl chloride-induced liver tumours are carcinogen-specific but vary with cell type and species.

Abstract

Previous studies have shown that a high proportion (5/6) of human liver angiosarcomas (ASL) associated with exposure to vinyl chloride (VC) contains a GC-->AT mutation at the Ki-ras codon 13. This mutation, however, has not been found in 5 ASL or 2 hepatocellular carcinomas (HCC) induced in rats by VC. These 2 HCC did contain a mutation at codon 61 of the Ha-ras gene. In order to extend this study and further explore the mechanisms of tumour induction, an additional 6 ASL and 6 HCC induced in rats by VC were analysed for ras gene point mutations, as well as 10 rat and 10 murine ASL induced by vinyl fluoride (VF), and 5 ASL, 6 Kupffer cell sarcomas, 4 HCC and 2 cholangiocellular carcinomas induced by Thorotrast in rats. Tumour DNA was analysed by PCR-SSCP and direct sequencing. None of the rodent ASL contained a mutation at codon 13 of the Ki-ras gene showing that the ras gene mutational pattern is species-specific. The CAA-->CTA mutation, previously found at codon 61 of the Ha-ras gene in rat HCC, was observed in 5 further VC-induced HCC but was not detected in the Thorotrast-induced HCC, suggesting carcinogen-specificity. This mutation was also absent in VC-induced ASL, which supports the cell-specificity of the ras mutational pattern in chemically induced tumours. No predominant mutation was detected in VF- and Thorotrast-induced tumours. Thus, a given mutation in a tumour may be carcinogen-specific but also depend on the species and the cell type.

• Authors: S Boivin-Angèle, L Lefrançois, O Froment, A Spiethoff, M S Bogdanffy, K Wegener, H Wesch, A Barbin, B Bancel, C Trépo, H Bartsch, J Swenberg, M J Marion
• Journal: International journal of cancer (Int J Cancer) Vol. 85 Issue 2 Pg. 223-7 (Jan 15 2000) ISSN: 0020-7136 [Print] United States
• PMID: 10629081 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2000 Wiley-Liss, Inc.

Chemical References

• Carcinogens
• Mutagens
• Vinyl Compounds
• vinyl fluoride
• Thorium Dioxide
• Vinyl Chloride

Topics

• Animals
• Carcinogens (toxicity)
• Carcinoma, Hepatocellular (chemically induced, genetics)
• DNA Mutational Analysis
• Exons
• Female
• Genes, ras
• Hemangiosarcoma (chemically induced, genetics)
• Liver Neoplasms (chemically induced, genetics)
• Male
• Mice
• Mutagenesis
• Mutagens (toxicity)
• Polymerase Chain Reaction
• Polymorphism, Single-Stranded Conformational
• Rats
• Rats, Sprague-Dawley
• Thorium Dioxide (toxicity)
• Vinyl Chloride (toxicity)
• Vinyl Compounds (toxicity)