Isolation and properties of Chinese hamster lung cells resistant to ellipticine derivatives

Chinese hamster lung cells resistant to 9-OH-ellipticine (9-OH-E) were selected in vitro by adding stepwise increasing drug concentrations to the cell growth medium. This selection procedure resulted in the isolation of two sublines, about tenfold and 12-fold resistant to 9-OH-E. This level of resistance did not increase even after about 30 months of drug exposure. Cytogenetic studies revealed that the resistant cells carry several discrete karyotype modifications, the most striking being the absence of one No. 5 chromosome and the presence of a marker chromosome characterized by peculiar G-banding. Development of 9-OH-E resistance was also associated with some changes in cell properties such as modifications of morphology and growth parameters, lower oncogenic potential, and cross-resistance to a variety of antitumor agents. Although these results suggest that the resistance is associated with a modification of cell membrane properties, drug uptake studies did not show any significant difference between the parental sensitive cells and the resistant sublines.