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Phorbol Esters Induce Changes in Adenosine Deaminase, Purine Nucleoside Phosphorylase, and Terminal Deoxynucleotidyl Transferase Messenger RNA Levels in Human Leukemic Cell Lines¹

Division of Immunology/Rheumatology, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8

We have studied the expression of mRNA encoding adenosine deaminase (ADA; EC 3.5.4.4), purine nucleoside phosphorylase (PNP; EC 2.4.2.1), and terminal deoxynucleotidyltransferase (TdT; EC 2.7.7.31) in different leukemic cell lines of B- and T-cell lineage. Incubation of leukemic cells in the presence of the phorbol esters, 12-O-tetradecanoylphorbol-13-acetate or phorbol 12,13-dibutyrate, resulted in reduction of ADA and TdT mRNA levels, while PNP mRNA levels increased under the same treatment. The effect of TPA on the activity of these enzymes correlated well with its effects on their mRNA levels. TPA caused a 40% decrease in ADA and a 60% decrease in TdT enzyme activity, after 6 h of treatment. In contrast, PNP activity increased up to 200% after 12 h of incubation with the phorbol ester.

The changes induced by the phorbol esters in the levels of mRNA of ADA, PNP, and TdT, and their enzyme activities in human leukemic cell lines mimic the changes in the activities of these enzymes in developing T-lymphocytes during differentiation in vivo, suggesting a role for protein kinase C in the regulation of ADA, PNP, and TdT gene expression during lymphoid cell differentiation.

¹ This work was supported by grants from the National Research Council of Canada and the National Cancer Institute of Canada.

² Supported by The Hospital for Sick Children Foundation, Postdoctoral Fellowship. To whom requests for reprints should be addressed, at Division of Immunology/Rheumatology, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8.

³ Recipient of a Medical Research Council of Canada, Postdoctoral Fellowship.

⁴ Recipient of the National Cancer Institute of Canada Scholarship.

Received 10/30/89. Revised 2/ 2/90.