Plasma membrane preparations from Chinese hamster lung cells, which are resistant to the antitumor agent Adriamycin, were analyzed using fluorescence polarization of the membrane lipid probe trans-parinaric acid. The results of these studies reveal that membranes from several drug-resistant isolates have a substantial decrease in lipid structural order relative to membranes from drug-sensitive cells. Additional studies have shown that certain isolates are unstable and undergo a sequential phenotypic reversion after continuous passage in culture. Thus, we have identified cells which have reverted for membrane lipid physical changes but which still remain highly resistant to Adriamycin. At later passages, these cells are found to revert to drug sensitivity. These results indicate that an alteration of plasma membrane lipid structural order is not an essential component of the Adriamycin-resistant phenotype. However, in certain isolates, drug resistance and changes in membrane physical properties are both associated with an unstable genetic element.
This investigation was supported in part by Research Grant CA-28120 from the National Cancer Institute, Department of Health and Human Services, and by American Cancer Society Grant IN-115, through the Mid American Cancer Center. This study is Contribution 82-437-j from the Kansas Agricultural Experiment Station, Division of Biology, Kansas State University, Manhattan, KS 66506.