Cytogenetic Alterations Associated with P-Glycoprotein- and Non-P-Glycoprotein-mediated Multidrug Resistance in SW-1573 Human Lung Tumor Cell Lines1

Multidrug resistance can be induced in mammalian cells by selection with a single cytotoxic agent. Overproduction of the energy-dependent drug efflux pump P-glycoprotein, encoded by the mtlrl gene, has been identified as the cause of one form of multidrug resistance. The molec ular basis of other forms of multidrug resistance is unknown. Doxorubicin selection of the human squamous lung cancer cell line SW-1573 resulted in multidrug-resistant sublines in which a non-P-glycoproteinmediated form of multidrug resistance precedes mdrl expression. Here we present a cytogenetic analysis of both non-P-glycoprotein-mediated multidrug-resistant and P-glycoprotein-mediated multidrug-resistant sublines derived from SW-1573. Three independently derived non-Pglycoprotein-mediated multidrug-resistant sublines showed a heterozy gous deletion of the short arm of chromosome 2 (p23-pter), whereas alterations of chromosome 7 were present in the P-glycoprotein-medi ated multidrug-resistant cell lines. In one series of clonali) derived P-glycoprotein-mediated multidrug-resistant sublines, mdrl overexpression was accompanied by various markers of chromosome 7 with breakpoints at 7q22, the mdrl gene being known to be located at 7q21.1. Our data suggest that in SW-1573 cells acquisition of non-P-glycopro tein-mediated multidrug resistance is accompanied by a specific deletion or a translocation involving the short arm of chromosome 2, whereas in the emergence of P-glycoprotein-mediated multidrug resistance a rear rangement of the long arm of chromosome 7 is a critical event.