Isolation of a clone of F9 teratocarcinoma cells "naturally" resistant to G418.

Resistance to the neomycin analogue G418 forms the basis of a dominant marker selection system for mammalian (and other) cells transfected with the bacterial neo gene. This system has been particularly effective because of the low incidence of spontaneous conversion to G418 resistance in mammalian cells; no case of resistance to the drug in the absence of the bacterial genes has yet been reported to our knowledge. During the course of transfection experiments, we recently isolated a clone of F9 teratocarcinoma cells which is drug resistant yet has no detectable integrated plasmid sequences, neo RNA transcripts, or aminoglycoside phosphotransferase activity. The G418-resistant clone (F9nr7) did not display enhanced resistance to other cytotoxic drugs tested: colchicine, actinomycin D, cycloheximide, and hygromycin B. Therefore, nr7 cells differ from multidrug-resistant phenotypes previously described. However, this clone is inhibited, relative to control cells, in its response to the differentiation-inducing drugs retinoic acid and dibutyryl cAMP, which suggests that some aspects of general drug metabolism may be altered in these cells.