Inhibition of intercellular communication by tumor-promoting phorbol esters

Cocultures were established of mouse epidermal cells (HEL/37) and mouse fibroblast cells (PG-19) deficient in the enzyme hypoxanthine-guanine phosphoribosyltransferase. Metabolic cooperation between the cocultured cells was detected as labeling of PG-19 cells on incubation of cocultures with [3H]-hypoxanthine. The transfer of label from HEL/37 cells to PG-19 cells was inhibited by the tumor prmoters 12-O-tetra-decanoylphorbol-13-acetate (10(-8) M) and phorbol-12,13-di-decanoate (10(-7) M) but not by nonpromoting derivatives of these phorbol esters. The inhibition was partially prevented by the antiinflammatory steroid fluocinolone acetonide, which is an antagonist of mouse skin tumor promotion, and by prolonged exposure of the cocultures to 12-O-tetradecanoylphorbol-13-acetate.