WORTMANNIN INHIBITS CARCINOGEN-STIMULATED PHOSPHORYLATION OF ETHANOLAMINE AND CHOLINE

We have previously reported that in C3H/10T1/2 fibroblasts the environmental carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) stimulated phosphorylation of ethanolamine (Etn). Here we show that in these fibroblasts DMBA also stimulates phosphorylation of choline (Cho). Wortmannin (50-200 nM), an established inhibitor of phosphatidylinositol-3-kinase (PI3K), significantly inhibited DMBA-induced phosphorylation of both Etn and Cho. Wortmannin also inhibited the effect of insulin, a major activator of PI3K, on DNA synthesis. However, insulin had no effect on the phosphorylation of Etn and Cho. These data suggest that a carcinogen-induced kinase phosphorylates both Etn and Cho, and that the inhibitory effect of wortmannin on Etn/Cho kinase activity may be unrelated to its inhibitory effect on PI3K activity.