ras gene mutations in vinyl chloride-induced liver tumours are carcinogen-specific but vary with cell type and species
✍ Scribed by Sandra Boivin-Angèle; Lydie Lefrançois; Olivier Froment; Andreas Spiethoff; Matthew S. Bogdanffy; Kurt Wegener; Horst Wesch; Alain Barbin; Brigitte Bancel; Christian Trépo; Helmut Bartsch; James Swenberg; Marie-Jeanne Marion
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- French
- Weight
- 88 KB
- Volume
- 85
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
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 VCinduced 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 cellspecificity 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. Int.