Stimulation of sterol and DNA synthesis in leukemic blood cells by low concentrations of phytohemagglutinin

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The response of leukemic cells from AKR/J mice to phytohemagglutinin (PHA) was compared with that of normal lymphocytes. PHA stimulated first cholesterol synthesis and then DNA synthesis in both lymphocytes and leukemic cells. The neoplastic cells were, however, much more sensitive to PHA, requiring less time and a lower concentration of the lectin for optimum stimulation as compared to lymphocytes. In fact, the amount of PHA which was required to activate lymphocytes to proliferate, as measured by increases in sterol and DNA synthesis, was inhibitory to leukemic cells. The basal level of cholesterol synthesis and the induction of cholesterol synthesis following PHA activation were depressed in lymphocytes and leukemic cells by treatment with 25-hydroxycholesterol and 7-ketocholesterol. These two oxygenated derivatives of cholesterol are known to be potent and specific inhibitors of sterol synthesis. Blockage of sterol synthesis by these reagents also abolished PHA-activated DNA synthesis in lymphocytes and leukemic cells. The results support the hypothesis that the synthesis of cholesterol is an important event leading to cell proliferation.