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ras gene mutations in vinyl chloride‐induced liver tumours are carcinogen‐specific but vary with cell type and species
Author(s) -
BoivinAngèle Sandra,
Lefrançois Lydie,
Froment Olivier,
Spiethoff Andreas,
Bogdanffy Matthew S.,
Wegener Kurt,
Wesch Horst,
Barbin Alain,
Bancel Brigitte,
Trépo Christian,
Bartsch Helmut,
Swenberg James,
Marion MarieJeanne
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000115)85:2<223::aid-ijc12>3.0.co;2-h
Subject(s) - point mutation , mutation , carcinogen , biology , microbiology and biotechnology , gene mutation , gene , thorotrast , carcinogenesis , cancer research , pathology , genetics , medicine
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. Int. J. Cancer 85:223–227, 2000. ©2000 Wiley‐Liss, Inc.