Inhibition of sterol and DNA synthesis in peripheral blood lymphocytes by AY9944.

The effect of the inhibitor of cholesterol synthesis AY9944 on DNA synthesis was tested in phytohemagglutinin stimulated lymphocytes incubated in delipidated serum. AY9944 caused a decrease in cholesterol synthesis from [14C] acetate and an accummulation of [14C] 7-dehydrocholesterol. This inhibition of cholesterol synthesis resulted in an inhibition of DNA synthesis in a dose related manner. Inhibition could be partly reversed by added lipoprotein. Inhibition of DNA synthesis occurred if AY9944 was added at the early stages of blast transformation but not when the response was well established. These findings suggest that some endogenous cholesterol synthesis may be required for the complete phytohemagglutinin stimulation of lymphocytes.