Rapid stimulation of phospholipid metabolism in bovine lymphocytes by tumor-promoting phorbol esters
Wertz, P.W.; Mueller, G.C.
Cancer Research 38(9): 2900-2904
1978
ISSN/ISBN: 0008-5472 PMID: 679198 Document Number: 125413
12-O-Tetradecanoylphorbol-13-acetate (TPA), a highly active tumor-promoting agent and lymphocyte comitogen, accelerates the incorporation of [methyl-3H]choline chloride ([3H-Me]choline) into the phospholipids of bovine lymphocytes. Chromatographic analysis of the phospholipids from lymphocytes exposed to 10-8 M TPA for varying intervals in the presence of [3H-Me]choline reveals a lag period of about 20 min, after which the rate of labeling of phosphatidylcholine, lysophosphatidylcholine and sphingomyelin are enhanced. Structure-activity studies show that the ability of phorbol diesters to accelerate [3H-Me]choline incorporation runs parallel to their potency as lymphocyte comitogens and tumor promoters. The response to TPA is insensitive to the inhibition of RNA and protein synthesis by actinomycin D and cycloheximide, respectively, and is also insensitive to the inhibition of membrane movement by cytochalasin B. Retinoic acid, an antagonist of the tumor-promoting and comitogenic actions of TPA, also blocks the acceleration of [3H-Me]choline incorporation into phospholipids by TPA. The bovine lymphocyte system may be useful for studies of the molecular mechanisms of action of tumor-promoting phorbol esters and their retinoid antagonists.