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Two-Stage Chemical Oncogenesis in Cultures of C3H/10T1/2 Cells¹

McArdle Laboratory for Cancer Research, The Medical School, University of Wisconsin, Madison, Wisconsin 53706

The initiation and promotion stages of chemical oncogenesis have been demonstrated in cultured C3H/10T1/2 mouse embryo cells. Treatment of the cells with a subeffective concentration of 3-methylcholanthrene, benzo(a)pyrene, or 7,12-dimethylbenz[a]anthracene, followed 4 days later by a nontransforming amount of tetradecanoylphorbol acetate (TPA), phorbol didecanoate, or 4--phorbol didecanoate, produced transformation. Phorbol was ineffective. TPA did not select for transformed cells. When TPA treatment preceded 3-methylcholanthrene, no enhancement of transformation was observed. When TPA was added immediately after hydrocarbon treatment, there was a significant inhibition of transformation. TPA did not exert promoting activity when the hydrocarbons were in high enough concentrations to produce appreciable transformation. The promoting action of TPA cannot be attributed only to a stimulation of cell division.

¹ This work was supported in part by Contracts N01-CP-53515 and N01-CP-65735 from the National Cancer Institute, NIH. A preliminary report of part of this work appeared perviously (20).

² American Cancer Society Professor of Oncology.

Received 1/16/76. Accepted 4/ 2/76.