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Substrate Requirements and Kinetic Analysis of the Cortisol Effects on Uridine Uptake and Incorporation by Mouse Lymphoma P1798 Cells in Vitro¹

Research Institute of the Hospital for Joint Diseases, Mount Sinai School of Medicine, New York, New York 10035

Cortisol markedly suppressed in vitro utilization of uridine-³H by corticoid-sensitive mouse lymphoma P1798 cells. Corticoid-resistant cells were not affected. Inhibition did not depend on reduced uptake of exogenous carbohydrate precursors since similar effects were obtained in glucose-free, pyruvate-free medium. Omission of glucose and pyruvate per se did not influence uridine-³H uptake and incorporation by tumor cells, but it substantially decreased nucleoside utilization by rat thymocytes. However, cortisol inhibited uridine-³H transport by thymocytes, whether or not glucose and/or pyruvate were present. Neither glucose alone nor glucose plus pyruvate could maintain maximal levels of uridine-³H uptake by P1798 lymphocytes. When tumor cells were incubated in a balanced salt solution supplemented with glucose alone or with glucose and pyruvate, cortisol inhibition of nucleoside utilization was approximately one-half of that observed in complete medium. Similar results were obtained in medium containing salts plus glutamine, even though uptake and incorporation of uridine were practically restored to control levels. Addition of the remaining amino acids to the glutamine-containing balanced salt solution reconstituted the full cortisol inhibition. Glucocorticoid treatment had no effect on tumor uridine kinase activity but decreased V_max of uridine-³H uptake without affecting apparent K_m. Our results suggest that reduced incorporation of uridine-³H into RNA after exposure of P1798 lymphocytes to glucocorticoids is a consequence of diminished precursor transport rather than of decreased phosphorylation and may not depend on prior inhibition of glucose uptake.

¹ This investigation was supported by USPHS Research Grant CA 10064 from the National Cancer Institute.

Received 1/29/74. Accepted 5/31/74.