Anitroxide-sterol derivative potently modifies cholesterol biosynthesis by normal and neoplastic guinea pig...

Leukemic guinea pig lymphocytes (L2C) synthesise cholesterol in vitro at a forty-fold greater rate than normal cells. Equilibration (18 h) with lecithin or lecithin-cholesterol liposomes, respectively, enhances or suppresses sterol manufacture by normal lymphocytes but does not influence sterol production by L2C cells. In contrast, greater than 5-10(9) molecules/cell of a nitroxide-derivative of androstane, (17 beta-hydroxy-4',4'-dimethylspiro [5 alpha-androstan-3,2'-oxazolidin]-3'-yloxyl), commonly used as a membrane spin-probe, drastically inhibit sterol roduction by both normal and leukemic cells (maximum within 2 H). At less than 5-10(9) molecules/cell, this sterol stimulates cholesterol synthesis. 25-Hydroxycholesterol at low concentrations also stimulates sterol manufacture, whereas high concentrations are also inhibitory in both cell types.