{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T13:47:22Z","timestamp":1761918442681},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,7,19]],"date-time":"2002-07-19T00:00:00Z","timestamp":1027036800000},"content-version":"vor","delay-in-days":199,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Vinyl chloride (VC) is a potent liver carcinogen that induces angiosarcomas in humans and animals. Recent evidence shows that liver tumors from patients with VC exposure may have a specific K\u2010<jats:italic>ras<\/jats:italic> mutation pattern. This study was performed to determine the status of K\u2010<jats:italic>ras<\/jats:italic>\u20102 in liver angiosarcomas (LAS) from workers occupationally exposed to VC. We examined the presence of K\u2010<jats:italic>ras<\/jats:italic>\u20102 mutations in 15 LAS from patients with known exposure to VC (median exposure: 8,260 ppm [range 3,900\u2013 21,000 ppm]]. In all cases, other risk factors for the development of LAS were excluded. Direct DNA sequencing after microdissection of the tumor cells was used for the analysis. Heterozygous mutations of K\u2010<jats:italic>ras<\/jats:italic>\u20102 were detected in 8\/15 LAS (53%). Five patients (33%) had a mutation of codon 12 and three of codon 13 (20%). The most common changes were G\u2192A transitions in five LAS which lead to the substitution of aspartic acid for glycine in the resulting p21 protein. In two patients (13%), mutations of the K\u2010<jats:italic>ras<\/jats:italic>\u20102 gene were identified in the adjacent nonneoplastic liver tissue. These data indicate that VC induces a high frequency of G\u2192A transitions in human LAS. This mutation pattern is likely a consequence of VC\u2010DNA\u2010adduct formation. Environ. Mol. Mutagen. 40:36\u201340, 2002. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/em.10084","type":"journal-article","created":{"date-parts":[[2002,10,6]],"date-time":"2002-10-06T11:53:08Z","timestamp":1033905188000},"page":"36-40","source":"Crossref","is-referenced-by-count":32,"title":["Mutation analysis of K\u2010<i>ras<\/i>\u20102 in liver angiosarcoma and adjacent nonneoplastic liver tissue from patients occupationally exposed to vinyl chloride"],"prefix":"10.1002","volume":"40","author":[{"given":"Markus","family":"Weihrauch","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Bader","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerhard","family":"Lehnert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Koch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Wittekind","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renate","family":"Wrbitzky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Tannapfel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,7,19]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"303","article-title":"Role 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