title: 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.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 271, Lyon, France.
authors.forename: S
authors.initials: S
authors.lastname: Boivin-Angèle
authors.forename: L
authors.initials: L
authors.lastname: Lefrançois
authors.forename: O
authors.initials: O
authors.lastname: Froment
authors.forename: A
authors.initials: A
authors.lastname: Spiethoff
authors.forename: M S
authors.initials: MS
authors.lastname: Bogdanffy
authors.forename: K
authors.initials: K
authors.lastname: Wegener
authors.forename: H
authors.initials: H
authors.lastname: Wesch
authors.forename: A
authors.initials: A
authors.lastname: Barbin
authors.forename: B
authors.initials: B
authors.lastname: Bancel
authors.forename: C
authors.initials: C
authors.lastname: Trépo
authors.forename: H
authors.initials: H
authors.lastname: Bartsch
authors.forename: J
authors.initials: J
authors.lastname: Swenberg
authors.forename: M J
authors.initials: MJ
authors.lastname: Marion
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D011905:Genes, ras; D006394:Hemangiosarcoma / Q000139:chemically induced / Q000235:genetics*; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D051379:Mice; D016296:Mutagenesis; D009153:Mutagens / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D051381:Rats; D017207:Rats, Sprague-Dawley; D013911:Thorium Dioxide / Q000633:toxicity; D014752:Vinyl Chloride / Q000633:toxicity*; D014753:Vinyl Compounds / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D009153:Mutagens; D014753:Vinyl Compounds; C016829:vinyl fluoride; D013911:Thorium Dioxide; D014752:Vinyl Chloride