Enhancement by TPA of phenotypes associated with transformation in carcinogen‐treated human cells: Evidence for a selective mechanism

The tumor promoter 12‐O‐tetradecanoylphorbol 13‐acetate (TPA) was found to increase the incidence of phenotypic alterations induced by the direct‐acting carcinogen N‐methyl‐N‐nitro‐N‐nitrosoguanidine (MNNG) in human endometrial stromal cells. Following carcinogen treatment, changes in saturation density, γ‐glutamyl‐transpeptidase expression, morphology, and growth in selective media were enhanced in cell cultures subjected to continuous TPA exposure as compared to cultures receiving ethanol vehicle. This enhancement may have resulted, at least in part, from selection of cells altered by carcinogen, as evidenced by differences in the colony‐forming abilities of MNNG‐treated and control cultures after prolonged TPA exposure, and by differences in morphologic response to TPA challenge in these two populations.