linoleic-acid and Leukemia--Lymphoid

The glucocorticoid sensitive CEM-C7 T cell line was derived from human acute lymphoblastic leukemia cells by Norman and Thompson (Cancer Res. 37 (1977) 3875). Madden et al. (Cancer Res 46 (1986) 617) have demonstrated that the growth inhibitory effect of glucocorticoids on these cells is due in part to an inhibition of cholesterol synthesis even in the presence of low-density lipoprotein (LDL)-containing serum. To delineate further the role of cholesterol in this growth inhibition, we have examined the ability of LDL-bound [3H]cholesterol linoleate to reverse the growth inhibitory effect of 1 microM dexamethasone on the CEM-C7 cells. LDL-bound cholesterol linoleate did not reverse the dexamethasone-mediated growth inhibition. Although incorporation of [14C]acetate into free cholesterol was inhibited only 20% by incubation with LDL, the presence of dexamethasone further inhibited acetate incorporation into free cholesterol in the LDL-treated cells. Dexamethasone had no effect on the uptake or utilization of LDL-bound cholesterol linoleate. Under all conditions, more than 99% of the acetate incorporated into cholesterol was present as free cholesterol, while over 80% of the LDL-derived cholesterol linoleate remained in the ester compartment. In contrast, in normal lymphocytes, over half the LDL-derived cholesterol was converted to free cholesterol. Direct analysis of the acid cholesterol ester hydrolase, the enzyme primarily responsible for processing LDL-bound cholesterol esters, revealed over 60-times the activity of this enzyme in the normal lymphocytes as compared to the activity present in the C7 cells. This finding cautions against the assumption that the presence of lipoprotein-containing serum provides an adequate, usable source of cholesterol for all cells.

Topics: Animals; Cell Division; Cell Line; Cholesterol; Cholesterol Esters; Cholesterol, LDL; Dexamethasone; Humans; Leukemia, Lymphoid; Linoleic Acid; Linoleic Acids; Mevalonic Acid; Mice; Phosphatidylcholines; T-Lymphocytes