{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T17:29:47Z","timestamp":1764782987765},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,7,19]],"date-time":"2006-07-19T00:00:00Z","timestamp":1153267200000},"content-version":"vor","delay-in-days":6774,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[1988,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The Syrian hamster embryo (SHE) cell transformation model has been used by many investigators to study the multistep process of neoplastic transformation induced by chemical carcinogens. In this study we have attempted to determine if activated proto\u2010oncogenes are present in the transformed cells induced by a variety of chemical carcinogens. Twelve carcinogen\u2010induced hamster cell lines, established by treatment of normal SHE cells with benzo[a]pyrene, diethylstilbestrol, or asbestos, were examined. One spontaneously transformed cell line (BHK\u2010A) was also studied. Some of the cell lines were also tested for oncogene activation at the preneoplastic stage, before they acquired tumorigenic potential. DNAs from normal, preneoplastic, and neoplastic cells were tested by transfection into mouse NIH 3T3 cells, and morphologically transformed foci were scored on the contact\u2010inhibited monolayer of 3T3 cells. The frequency of focus formation for normal SHE cell DNA was &lt;0.0008 foci\/\u03bcg DNA, while approximately 40% (5 of 12) of the DNAs from carcinogen\u2010induced, tumorigenic hamster cell lines induced foci at a frequency of \u2a7e 0.012 foci\/\u03bcg DNA. The other seven carcinogen\u2010induced cell lines and the BHK\u2010A cells were negative (&lt;0.002 foci\/\u03bcg DNA). When the DNAs from transformed foci induced by the five positive cell lines were retransfected into NIH 3T3 cells, the frequency of secondary foci of 3T3 cells was as much as 50\u2010fold higher (1.34 foci\/\u03bcg DNA) than with the primary transfectants. DNAs from transformed foci or tumors derived from transformed foci were screened by Southern blot analyses with known oncogenes and with a hamster repetitive DNA probe for the presence of transfected hamster oncogenes. Newly acquired hamster Ha\u2010<jats:italic>ras<\/jats:italic> sequences were detected in transformed 3T3 cells induced by four of the five hamster tumor DNAs. Immunoprecipitation of lysates of several secondary transformants with a ras monoclonal antibody (Y13\u2013259) showed altered gel mobility of the p21<jats:sup>ras<\/jats:sup> protein consistent with a mutation at codon 12. These activated ras genes were detected by the NIH 3T3 assay in the tumorigenic hamster cells but not in the preneoplastic, immortal cell from which they were derived. The activated Ha\u2010ras proto\u2010oncogene was detected in cell lines induced by each of the three different carcinogens studied. Cells from transformed foci inauced by DNA from one of the hamster tumor cell lines (BP6T) contained hamster sequences but did not show newly acquired Haras, Ki\u2010<jats:italic>ras<\/jats:italic>, or N\u2010ras genes on Southern analysis or altered p21<jats:sup>ras<\/jats:sup> protein. The transforming gene in this cell line appears to be a non\u2010<jats:sup>ras<\/jats:sup> oncogene. These observations indicate that \u223c40% of the chemically transformed Syrian hamster tumor cell lines have activated Ha\u2010ras oncogenes. The activation of Ha\u2010ras proto\u2010oncogene is a late, postimmortalization step in the neoplastic progression of SHE cells. Only one cell line with a non\u2010<jats:sup>ras<\/jats:sup> oncogene was detected in the NIH 3T3 focus assay, and \u223c60% of the cell lines were inactive in this assay, indicating the need to develop alternative assay systems for oncogene activation. Some of the preneoplastic Syrian hamster cell lines may be useful for this purpose.<\/jats:p>","DOI":"10.1002\/mc.2940010306","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T19:34:18Z","timestamp":1172086458000},"page":"180-188","source":"Crossref","is-referenced-by-count":18,"title":["Characterization of activated proto\u2010oncogenes in chemically transformed syrian hamster embryo cells"],"prefix":"10.1002","volume":"1","author":[{"given":"Tona M.","family":"Gilmer","sequence":"first","affiliation":[]},{"given":"Lois A.","family":"Annab","sequence":"additional","affiliation":[]},{"given":"J. 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