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Titolo:
High prevalence of K-ras-2 mutations in hepatocellular carcinomas in workers exposed to vinyl chloride
Autore:
Weihrauch, M; Benicke, M; Lehnert, G; Wittekind, C; Bader, M; Wrbitzky, R; Tannapfel, A;
Indirizzi:
Hannover Med Sch, Abt Arbeitsmed, D-30625 Hannover, Germany Hannover Med Sch Hannover Germany D-30625 med, D-30625 Hannover, Germany Univ Leipzig, Inst Pathol, D-7010 Leipzig, Germany Univ Leipzig Leipzig Germany D-7010 Inst Pathol, D-7010 Leipzig, Germany Univ Erlangen Nurnberg, Inst Poliklin Arbeits, Erlangen, Germany Univ Erlangen Nurnberg Erlangen Germany klin Arbeits, Erlangen, Germany
Titolo Testata:
INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH
fascicolo: 6, volume: 74, anno: 2001,
pagine: 405 - 410
SICI:
0340-0131(200108)74:6<405:HPOKMI>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAS GENE-MUTATIONS; POLYMERASE-CHAIN-REACTION; LIVER-TUMORS; MONOMER WORKERS; POINT MUTATIONS; EXPRESSION; CANCER; ACTIVATION; ELECTROPHORESIS; CARCINOGENESIS;
Keywords:
vinyl chloride; HCC; K-ras-2 mutation pattern;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Weihrauch, M Hannover Med Sch, Abt Arbeitsmed, Carl Neuberg Str 1, D-30625Hannover, Germany Hannover Med Sch Carl Neuberg Str 1 Hannover Germany D-30625
Citazione:
M. Weihrauch et al., "High prevalence of K-ras-2 mutations in hepatocellular carcinomas in workers exposed to vinyl chloride", INT A OCCUP, 74(6), 2001, pp. 405-410

Abstract

Objectives: Vinyl chloride (VC) and its metabolites are human carcinogens associated with liver angiosarcomas (LAS) and also with hepatocellular carcinomas (HCCs). In VC associated LAS mutations of the K-ras-2 gene have beenreported; however, no data about the prevalence of such mutations in VC-associated HCCs are available. The aim of the study was to evaluate possible specific K-ras-2 oncogene mutations in the case of HCCs due to VC. Methods:The presence of K-ras-2 mutations was analysed in tissue from 12 patients with VC-associated HCCs. All patients had known longterm exposure to VC (average exposure amount: 9,942 ppm-years). Twenty patients with hepatocellular carcinoma due to hepatitis B (n = 7), hepatitis C (n = 5) and alcoholic liver cirrhosis (n = 8) served as a control group. The specific mutations were determined by direct sequencing of codons 12 and 13 of the K-ras-2 gene in carcinomatous and adjacent non-neoplastic liver tissue after microdissection. Immunohistochemical analysis was performed to detect p21(ras) protein. Results: K-ras-2 mutations were found in five of 12 (42%) examined HCCs and in three cases of adjacent non-neoplastic liver tissue (25%). There werethree guanine to adenine (G --> A) point mutations in the tumour tissue. All three mutations found in non-neoplastic liver from VC-exposed patients were also G --> A point mutations (codon 12- and codon 13-aspartate mutations). Within the control group, K-ras-2 mutations were found in three of 20 (15%) examined HCCs. Conclusions: Mutations of the K-ras-2 gene in hepatocellular carcinomas associated with VC exposure are frequent events. We observed a K-ras-2 mutation pattern characteristic of chloroethylene oxide, one of the carcinogenic metabolites of VC analysed in animal models. Our resultssuggest that VC had direct toxic effects not only on endothelial cells butalso on hepatocytes, as it was previously only described in animal models.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 16:13:53