Pleiotropic Phenotype of Cultured Murine Cells Resistant to Maytansine, Vincristine, Colchicine, and Adriamycin23

Abstract

A noncloned subline of 3T3FL cells was developed that was resistant to the toxicity of the ansamycin alkaloid maytansine. Culture of 3T3FL cells with serially increasing concentrations of maytansine resulted in a cell line resistant to maytansine at concentrations 118-fold higher than concentrations cytotoxic for parental cells. Resistant cells (3T3^r) exhibited cross-resistance to colchicine, vincristine, adriamycin, and, to a lesser extent, cytochalasin B. Studies of binding and uptake of tritiated colchicine suggested that drug resistance of 3T3^r cells might reflect decreased uptake of drug without decreased binding to surface receptors. Murine sarcoma virus transformed 3T3^r cells less efficiently than 3T3FL cells.