TPA affects early and late stages of chemically-induced transformation in mouse submandibular salivary epithelial cells in vitro.

Abstract

The tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), is a potent mitogen in mouse submandibular epithelial cells in vitro. Effects of TPA were investigated on various stages in the transformation of this cell type by the carcinogen benzo[a]pyrene. There was no evidence of enhancement of the frequency of induction of foci of preneoplastic epithelial cells following a high, transforming dose of carcinogen, but TPA promoted this early stage in transformation if given at weekly intervals after a subthreshold, initiating exposure to carcinogen. Foci from all TPA-treated cultures appeared earlier and grew in size more rapidly than those induced by carcinogen alone. There was no evidence from these experiments, however, that foci from TPA-treated cultures were more likely to give rise to permanent epithelial cell lines or that these cell lines became tumorigenic earlier. Preliminary results showed that one out of two permanent, preneoplastic epithelial cell lines examined responded to the promoter at a late stage in transformation by showing enhanced tumorigenicity in syngeneic animals.