Co-mitogenic tumor promoters suppress the phosphatidylinositol response in lymphocytes during early mitogenesis.
The tumor-promoting agents 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and phorbol-12,13-dibenzoate inhibited the increased accumulation of [32P]phosphatidylinositol (PI) induced in mouse spleen lymphocytes by mitogenic lectins in the presence of [32P]orthophosphate. Similar inhibition of [32P]PI levels by TPA was seen in human tonsil T-lymphocytes stimulated with phytohemagglutinin. Only co-mitogenic phorbol esters prevented the [32P]PI accumulation during early mitogenesis. No increased 32P-labelling due to mitogen or decreases due to TPA was observed when cells were equilibrated with [32P]orthophosphate for 24 h prior to stimulation with mitogen, from which it is concluded that the total concentrations of phosphatidylcholine (PC) and PI are unaffected by mitogen or co-mitogen. The [32P]PI elevation but not the [32P]PC elevation was proportional to T-cell mitogenic potency for the lectins concanavalin A, divalent succinyl concanavalin A and phytohemagglutinin, and was prevented in each case by 5 X 10(-8) M TPA. Escherichia coli lipopolysaccharide did not give increased 32P incorporation into PI or PC, and TPA had no effect on 32P labelled phospholipid levels in the presence of this B-cell mitogen. The results indicate that the phosphatidylinositol response is not an invariable correlate of T-cell mitogenesis by polyclonal mitogens.
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000494:pharmacology
D002273:Carcinogens; D010703:Phorbol Esters; D010704:Phorbols; D010710:Phosphates; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D010835:Phytohemagglutinins; C008875:phorbol-12,13-dibenzoate; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine; C033085:phorbol