Ras gene mutations in vinyl chloride-induced liver tumours are carcinogen-specific but vary with cell type and species.
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.
Boivin-Angèle
S
S
Institut National de la Santé et de la Recherche Médicale, Unité 271, Lyon, France.
Lefrançois
L
L
Froment
O
O
Spiethoff
A
A
Bogdanffy
M S
MS
Wegener
K
K
Wesch
H
H
Barbin
A
A
Bancel
B
B
Trépo
C
C
Bartsch
H
H
Swenberg
J
J
Marion
M J
MJ
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*
D002273:Carcinogens; D009153:Mutagens; D014753:Vinyl Compounds; C016829:vinyl fluoride; D013911:Thorium Dioxide; D014752:Vinyl Chloride