Effect of 12-O-tetradecanoylphorbol-13-acetate on two charateristics of transformation acquired sequentially by ENU-exposed rat brain cells.

Cultures derived from rat brains at different times during the latent period of brain-tumour induction by N-ethyl-N-nitrosourea (ENU) showed increased plasminogen activator (PA) activity before being able to form colonies in agar. Control cultures from buffer-exposed animals showed neither property at comparable passages. More detailed investigations, using a culture derived from foetal brains only 2 days after exposure to ENU and clones from this culture, showed a sequence of low PA activity, then increased activity, followed by the ability to form colonies in agar, suggesting progressive transformation of cells in culture. Continuous culturing in the presence of the mouse skin tumour promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), did not accelerate the rate at which these two properties were acquired, but did cause a much greater increase of PA activity once this started to rise. If included in the assay mixture TPA also increased the PA activity of the cells. It therefore appears that in this system TPA can modulate PA activity under certain circumstances.