Interactions between adenovirus, a tumor promoter, and chemical carcinogens in transformation of rat embryo cell cultures.

Abstract

The tumor-promoting agent 12-O-tetradecanoyl-phorbol-13-acetate (TPA) caused a 2- to 3-fold enhancement of transformation of secondary rat embryo cells that had been injected with a temperature-sensitive mutant of adenovirus type 5(H5ts 125). In addition, transformed foci appeared earlier and were larger in cultures grown in the presence of TPA. The addition of TPA could be delayed until up to 7 days after viral injection and still enhancement was observed. Exposure of the cells to 7,12-dimethylbenz[a]pyrene prior to H5ts125 infection also resulted in a 2- to 4-fold enhancement of transformation, and this enhancement was further augmented 2- to 3-fold when cells were grown in TPA after virus infection. Whereas TPA did not enhance the cloning efficiency of normal rat embryo cells, it did enhance the cloning efficiency of isolated colonies of adenovirus-transformed cells when these were grown alone or cocultured with a 100-fold excess of normal rat embryo cells. The enhancement of adenovirus transformation by TPA appears to be due to its ability to facilitate expression of the transformed state rather than an effect on virus uptake or integration.