Pleiotropic phenotype of cultured murine cells resistant to maytansine, vincristine, colchicine, and adriamycin.

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 (3T3r) 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 3T3r cells might reflect decreased uptake of drug without decreased binding to surface receptors. Murine sarcoma virus transformed 3T3r cells less efficiently than 3T3FL cells.