INHIBITORS OF STEROL SYNTHESIS - SUBMICROMOLAR A-ETHYL-5-ALPHA-CHOLEST-7-ENE-3-BETA,15-ALPHA-DIOL CAUSES A MAJOR MODIFICATION OF THE STEROLCOMPOSITION OF CHO-K1 CELLS AND A MARKED CHANGE IN CELL MORPHOLOGY

Incubation of Chinese hamster ovary cells (CHO-K1) with 14 alpha-ethyl -5 alpha-cholest-7-ene-3 beta,15 alpha-diol (0.1 mu) in lipid-deficien t medium led to a major change in cellular sterol composition, which w as characterized by a very marked accumulation of C-30 sterols (lanost erol and 24,25-dihydrolanosterol). The accumulation of C-30 sterols wa s associated with a striking change in cell morphology. The change in cell shape (elongation) was similar to that described previously (A. W . Hsie and T, T. Puck, 1971. Proc. Natl. Acad. Sci. USA, 68: 358-361; and confirmed herein) for CHO-KI cells incubated in the presence of di butyryl cAMP (1 mM). This change in morphology, induced by dibutyryl c AMP, was not accompanied by a change in cellular sterol composition. T he cell elongation and accumulation of C-30 sterols, induced by the 14 alpha-ethyl diol, were prevented by the addition of cholesterol (10 m u M or 100 mu M) and were reversed by removal of the 14 alpha-ethyl di ol from the incubation medium. Incubation of the cells with the 14 alp ha-ethyl diol had no effect on the levels of cAMP under the conditions studied. Incubation of the cells with miconazole (10 mu 3) or with la nosterol (10 mu M) was also associated with the accumulation of C-30 s terols and an elongation of the tells. 24,25-Dihydrolanosterol (10 mu M) also induced similar changes in cellular morphology. The results pr esented herein demonstrate that marked changes in the sterol compositi on of CHO-K1 cells can be effected by incubation of the cells with 14 alpha-ethyl-5 alpha-cholest-7-ene-3 beta,15 alpha-diol, miconazole, or lanosterol. In addition, the findings reported herein indicate an imp ortant role of sterols in the control of the shape of these cells.