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On the Characteristics of Actinomycin D Resistance in L5178Y Cells¹

Department of Pharmacology and Toxicology and Division of Oncology, University of Rochester School of Medicine, Rochester, New York 14620

A subline of the L5178Y murine leukemia was selected for resistance to actinomycin D by drug administration in vivo. The resistant line, L5178Y/D, had impaired capacity for uptake of actinomycin D in vivo and in culture but not under nongrowing conditions. Administration of the drug in vivo (50 µg/kg) or in culture (0.1 µg/ml) inhibited uridine incorporation into RNA by L5178Y but not by L5178Y/D. An altered cell surface glycoprotein fraction was found in L5178Y/D. Enzymatic studies showed that levels of glycoprotein transferases catalyzing formation of amino acid-sugar and sugar-sugar bonds were generally higher, while specific activities of glycosidases were generally lower in L5178Y/D. Alterations in membrane composition and conformation in the drug-resistant subline could account for the observed changes in actinomycin D permeability.

¹ Supported by Contract NIH 69-39 with Chemotherapy, National Cancer Institute, NIH; Grant CA 11198-01 from NIH; Grant 1-P11-GM-15910 from the National Institute of General Medical Sciences, NIH; Grant P529 from the American Cancer Society; and a grant from the Monroe County Cancer and Leukemia Association.

² Research Career Development Awardee of the National Institute of General Medical Sciences.

Received 4/23/70. Accepted 7/21/70.

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