Vincristine‐resistant Human Cancer KB Cell Line and Increased Expression of Multidrug‐resistance Gene

A multidrug‐resistant clone of human cancer KB cells was isolated by stepwise selection on exposure to increasing doses of vincristine. The final clone, VJ‐300, obtained after ethylmethane sulfonate mutagenesis showed 400‐fold higher resistance to vincristine than did KB cells. Cellular accumulation of vincristine in VJ‐300 was decreased to less than one‐tenth of that in KB. The cells were also cross‐resistant to daunomycin, adriamycin, actinomycin D, colchicine and VP‐16. During continuous culturing in the absence of any drug for several months, a different colchicine‐resistant and multidrug‐resistant clone, KB‐C1, reverted almost completely to drug sensitivity, whereas drug resistance in VJ‐300 was stably maintained. Amplification of the multidrug‐resistance‐1 (mdr‐1) gene was more than 20‐fold in KB‐C1, but less than 2‐fold in VJ‐300, mdr‐1 mRNA was, however, expressed in VJ‐300 at a rate comparable to KB‐C1. Acquisition of high multidrug resistance in VJ‐300 might be correlated with both activated transcription of mdr‐1 gene and amplification.