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The Effects of Isoproterenol and Cyclic Adenosine 3',5'-Phosphate on Phytohemagglutinin-stimulated DNA Synthesis in Lymphocytes Obtained from Patients with Chronic Lymphocytic Leukemia¹

Department of Biochemistry and Molecular Biology, University of Oklahoma School of Medicine, and Biochemistry Section, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104

Peripheral blood lymphocytes obtained from patients with chronic lymphocytic leukemia were maintained in tissue culture and treated with isoproterenol, cyclic 3',5'-AMP, dibutyryl cyclic 3',5'-AMP, and theophylline either before or after addition of the mitogen phytohemagglutinin. The ability of the lymphocytes to undergo DNA synthesis was measured with a 6-hr incorporation of thymidine-³H, and the values obtained were compared with nontreated, phytohemagglutinin-stimulated chronic lymphocytic leukemia controls and lymphocytes from normal donors.

The results demonstrate that isoproterenol, cyclic 3',5'-AMP, and dibutyryl cyclic 3',5'-AMP markedly depress DNA synthesis, with the greatest inhibition obtained when the drugs were added within 24 hr after stimulation. The effects of isoproterenol are potentiated by theophylline, and the inhibition obtained with isoproterenol alone parallels that of dibutyryl cyclic 3',5'-AMP.

These findings suggest that cyclic 3',5'-AMP may be involved in the regulation of DNA synthesis in chronic lymphocytic leukemia lymphocytes.

¹ This work was supported by Grant CA-10683 from the National Cancer Institute, NIH, USPHS.

Received 3/ 2/70. Accepted 7/29/70.