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Enzymatic and Nutritional Evidence for Two-Stage Expression of the Asparagine Synthetase Locus in L5178Y Murine Leukemia Mutants¹

Departments of Pharmacology and of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06510

The initial mutation of the asparagine-dependent L5178Y murine lymphoblastic leukemia cells to asparagine independence is associated with the appearance of a regulated asparagine synthetase activity which is derepressed twofold when the cells are subcultured in asparagine-free medium. The 12-hr period required for derepression coincided with the time required to eliminate a lag in the rate of cell growth. The enzyme activity in these derepressed cells could be repressed by the addition of asparagine to the medium and a 12-hr half-life for the enzyme was calculated. Eleven independently derived substrains of spontaneous mutational origin exhibited the same degree of repressional control. Further long-term growth of these substrains in asparagine-free medium selected populations that had a higher constitutive level of asparagine synthetase which was not subject to repressional control.

¹ Supported by Grants CA 10748, CA 5012, CA 06519, and ACS IC64L.

² Present address: Children's Cancer Research Foundation, Inc., Boston, Mass. 02115.

³ Present Address: Radiobiology Laboratories, Yale University School of Medicine.

⁴ American Cancer Society Career Professor of Pharmacology; to whom requests for reprints should be sent.

Received 5/13/74. Accepted 7/19/74.