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Phenotypic Properties and Tumor Promoter-induced Alterations in Rat Embryo Cells Transformed by Adenovirus¹

Cancer Center/Institute of Cancer Research and the Division of Environmental Science, Columbia University College of Physicians and Surgeons, New York, New York 10032 [P. B. F., I. B. W.], and Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104 [N. I. G.]

Seven clones of secondary rat embryo cells transformed by a temperature-sensitive mutant of human adenovirus type 5 were analyzed to determine whether transformants obtained from cultures treated with chemical carcinogen prior to virus infection had a different phenotype than those obtained from cultures treated with virus alone. In addition, the effects of prolonged serial passage and the effects of exposure of the clones to 12-O-tetradecanoylphorbol-13-acetate on the expression of several markers of transformation were also determined. When compared to normal secondary rat embryo cells, most of the transformants had a reduced populationdoubling time, increased saturation density, reduced serum requirement, increased plasminogen activator production, reduced large external transformation-sensitive protein, increased lectin agglutinability, and decreased anchorage dependence (i.e., growth in agarose and agar). Prolonged serial passage of the transformants led to a spontaneous increase in cloning efficiency in agar. There was no consistent difference between the phenotypes of transformants obtained from cultures treated with carcinogen plus virus or those of transformants obtained with virus alone, although clones obtained from the carcinogen-plus-virus treatment appeared to express anchorage independence at earlier subpassages. The most striking finding was that 12-O-tetradecanoylphorbol-13-acetate caused an appreciable enhancement of the growth in agar of all of the transformants. Two early-passage-transformed clones grew in agar only in the presence of 12-O-tetradecanoylphorbol-13-acetate. The tumor promoter also increased the saturation densities and enhanced the cloning efficiencies in liquid medium of most of the transformants. These effects were not as striking with normal secondary rat embryo cells.

These results suggest that following adenovirus transformation there is a spontaneous progression in the expression of markers of transformation and that the phorbol ester tumor promoters can accelerate this process.

¹ Research was supported by Contract N01-CP-2-3234 from the National Cancer Institute, Department of Health, Education and Welfare and Grant 5 F32 CA 05640-02 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at Division of Environmental Sciences, Institute of Cancer Research, College of Physicians and Surgeons of Columbia University, 701 West 168th Street, New York, N.Y. 10032.

Received 11/10/78. Accepted 5/ 3/79.

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