EFFECT OF PHORBOL ESTERS ON CLONAL CULTURES OF HUMAN, HAMSTER, AND RAT RESPIRATORY EPITHELIAL-CELLS

Abstract

The effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on the growth of epithelial cells from rat, hamster, and human respiratory tract has been measured by monitoring colony formation and cross-linked envelope formation in culture. TPA and its active derivatives stimulated colony formation of rat tracheal epithelial cells but did not stimulate cross-linked envelope formation. Tracheal epithelial cells from the hamster and human bronchial epithelial cells were inhibited from forming colonies by these agents. This inhibitory effect was also dependent on concentration. In the rat, the stimulation of cells to enter cell division induced by TPA decayed with time after removal of primary cells from the trachea, while in hamsters and human cells, the inhibitory effect of TPA was independent of time. Although TPA inhibited colony formation in hamster and hamster cells, it did not elicit the same responses with respect to cross-linked envelopes. Hamster tracheal epithelial cells did not form cross-linked envelopes in response to TPA, whereas human bronchial cells did. A comparison was made of the response to TPA in cells from the human bronchi of 24 individuals; the extent of inhibition of colony formation induced by TPA varied by 130-fold. These results show that normal cells from these species vary in biological response to tumor promoters, implying that selective induction of terminal differentiation in normal cells may not be a universal mechanism of action of tumor promoters.