6533b86ffe1ef96bd12ce7ca

RESEARCH PRODUCT

Role of the Ha-ras gene in the malignant transformation of rat liver oval cells.

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description

We have shown that the oval cell line OCICDE 22 can be transformed by the highly carcinogenic fiord-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 OCICDE 22 cells any point mutations were detected in the ras proto-oncogene. The results indicate that the malignant transformation of OCICDE 22 cells by the 4 stereoisomeric benzo[c]phenan-threne 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 proto-oncogene in the transformed OCICDE 22 cell lines. However, transfection of the OCICDE 22 cells with an activated Ha-ras oncogene malignantly transformed the OCICDE 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 OCICDE 22 cells are committed to the bile duct epithelial cell lineage.