12-O-tetradecanoyl-phorbol-13-acetate enhancement of the tumorigenic potential of herpes simplex virus type 2 transformed cells.

The consequences of tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) interaction with clonal HSV-2-transformed nontumorigenic and weakly tumorigenic cells were studied. Enhancement of anchorage-independent growth (cloning efficiency) occurred in a dose-dependent manner when transformed but not nontransformed cells were pretreated with TPA. All subclonal nontumorigenic cell lines progressed to become tumorigenic after 20 serial passages in the presence of TPA. Also, subclonal, weakly tumorigenic cell lines were enhanced in tumorigenic potential (measured by reduced latent period for tumor formation) after transient treatment with TPA. In summary, TPA irreversibly enhanced the cloning efficiency and tumorigenic potential of transformed cells long after initiation by the virus.