On the characteristics of actinomycin D resistance in L5178Y cells.

A subline of the L5178Y murine leukemia was selected for resistance to actinomycin D by drug administration in vivo. The resistant Une, 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 jug/kg) or in culture (0.1 jug/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 acidsugar and sugar-sugar bonds were generally higher, while specific activities of glycosidases were generally lower in L5178Y/D. Alterations in membrane composition and con formation in the drug-resistant subline could account for the observed changes in actinomycin D permeability.