Gene amplification in multidrug‐resistant cells: Molecular and karyotypic events

Multidrug resistance (MDR) is developed in a population of somatic mammalian cells in vivo or in vitro when they are selected for resistance to each of a large group of drugs (colchicine, adriamycin, actinomycin D, etc.). It is produced by the amplification of some unknown gene(s) whose product(s) evidently change(s) the plasma membrane permeability of a cell to a selective agent and to other unrelated compounds. A large specific genomic region (150–250 kbp) undergoes amplification in MDR cells selected for the resistance to different drugs. Amplified DNA is located in homogeneously staining regions of chromosomes, double minute chromosomes and small chromatin bodies – episome‐like structures that replicate out of the S‐phase of a cell cycle. The selection of MDR cell variants is accompanied by regular karyotypic evolution specific for this type of drug resistance.