First Author | Boivin-Angèle S | Year | 2000 |
Journal | Int J Cancer | Volume | 85 |
Issue | 2 | Pages | 223-7 |
PubMed ID | 10629081 | Mgi Jnum | J:59263 |
Mgi Id | MGI:1351257 | Doi | 10.1002/(sici)1097-0215(20000115)85:2<223::aid-ijc12>3.0.co;2-h |
Citation | Boivin-Angele S, et al. (2000) Ras gene mutations in vinyl chloride-induced liver tumours are carcinogen-specific but vary with cell type and species. Int J Cancer 85(2):223-7 |
abstractText | 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. Copyright 2000 Wiley-Liss, Inc. |