Role of the Ha-ras gene in the malignant transformation of rat liver oval cells.
We have shown that the oval cell line OC/CDE 22 can be transformed by the highly carcinogenic fjord-region diol epoxides of benzo[c]phenanthrene. Mutational activation of the ras proto-oncogene family has been proposed to be a critical event in the formation of tumors induced by polycyclic aromatic hydrocarbons. Therefore, we investigated whether in the earlier transformed OC/CDE 22 cells any point mutations were detected in the ras proto-oncogene. The results indicate that the malignant transformation of OC/CDE 22 cells by the 4 stereoisomeric benzo[c]phenanthrene diol epoxides in vitro is independent of activation of the Ha-ras proto-oncogene. In addition, Northern and Western blot analyses revealed no overexpression of the Ha-ras protooncogene in the transformed OC/CDE 22 cell lines. However, transfection of the OC/CDE 22 cells with an activated Ha-ras oncogene malignantly transformed the OC/CDE 22 cells, and the transfected cells served as precursor cells of tumors with a cholangiocellular morphology and phenotype. Our latter finding reinforces the view that OC/CDE 22 cells are committed to the bile duct epithelial cell lineage.
Steinberg
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Institute of Toxicology, University of Mainz, Germany. steinber@mzdmza.zdv.uni-mainz.de
Frank
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Odenthal
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Dienes
H P
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Seidel
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D000818:Animals; D001652:Bile Ducts / Q000166:cytology; D002273:Carcinogens; D002277:Carcinoma / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line / Q000187:drug effects; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics*; D004847:Epithelial Cells; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D008099:Liver / Q000166:cytology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics*; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000648:ultrastructure; D010616:Phenanthrenes; D000090063:Proto-Oncogene Mas; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000235:genetics
D002273:Carcinogens; C000715470:MAS1 protein, human; D010616:Phenanthrenes; D000090063:Proto-Oncogene Mas; C090203:1,2-epoxy-3,4-dihydroxy-1,2,3,4-tetrahydrobenzo(c)phenanthrene