Rapid stimulation of phospholipid metabolism in bovine lymphocytes by tumor-promoting phorbol esters.

12-O-Tetradcanoylphorbol-13-acetate(TPA), a highly actIvetumor-promotingagentand lymphocytecomftogen, accelerat•s the incorporationof (methyI-3Hlchollnechio ride a3H-Mejcholine) b@tothe phospholipidsof bovine lymphocytes. Chromatographicanalysis of the phoepholipidsfrom lymphocytes exposed to 1O@u TPA for varying Intervals in the presenceof (3H-Mejcholln. reveals a lag periodof about 20 mm, after which the rate of labeling of phospha tidylcholine,lysophosphatidyicholins, and sphingomyelin are all enhanced.Structurs-activitystudiesshowthat the ability of phorbol diesters to accelerate [3H-Msjcholine incorporationrunsparallelto their potencyas lymphocyte comitog•ns and as tumor promot.rs. The response to TPA is insensitiveto the inhibitionof RNA and protein synthesisby actinomycinD and cycloheximide,respec tively, and is also insensitiveto the Inhibitionof mem brine movement by cytochalasin B. Retinoic acid, an antagonist of the tumor-promoting and comftogenic ac tions of TPA, also blocks the acc•leration of [3HMe]choline Incorporation into phospholipids by TPA. These observationssuggestthat the bovine lymphocyte systemmay be usefulfor studiesof the molecularmach anismsof action of tumor-promotingphorbolesters and their retinoidantagonists.