Chinese hamster ovary cell variants resistant to monensin, an ionophoric antibiotic. I. Isolation and altered endocytosis of ricin

Abstract

Chinese hamster ovary (CHO) cell variants resistant to a carboxylic ionophore, monensin, have been isolated. Two monensinresistant variants (Mon^R–;31 and Mon ^R–32) showed a three- to fourfold higher resistance to monensin than did CHO. These Mon^R clones also showed fourfold higher resistance to another carboxylic ionophore, nigericin, and twofold higher resistance to valinomycin. They were also slightly more resistant to other unrelated drugs such as adriamycin, colchicine, bleomycin, and chloroquine, and in particular, they showed about threefold higher resistance to ricin, a toxin of Ricinus communis. Mon^R clones were found to retain a normal level of [¹²⁵l]ricin binding, but internalization of [¹²⁵l]ricin into the Mon^R clones was one-half or less than with CHO. Present data suggest that drug-resistant clones selected in culture may provide a way to isolate cells with altered response to various bioactive molecules.