ACQUISITION OF MULTIPLE-DRUG RESISTANCE BY CCRF-CEM CELLS SELECTED FOR DIFFERENT DEGREES OF RESISTANCE TO VINCRISTINE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 68  (6) , 831-839
Abstract
The acquisition of multiple drug resistance to several natural product drugs by cultured human leukemic lymphoblasts selected for increasing resistance to vincristine (VCR) was studied. The following 3 apparent types of cross-resistance patterns were distinguished: specific, pleiotropic and mixed. Cross-resistance to vindesine developed in parallel with VCR resistance, appearing at the lowest levels of VCR resistance (.apprx. 5-fold). Vinblastine resistance did not become noticeable until VCR resistance was higher (.apprxeq. = 50- to 100-fold). Cross-resistance to 3 other tubulin-binding agents developed in a different pattern, however. While cross-resistance to maytansine was seen in cells of intermediate(.apprxeq. 50-fold) resistance to VCR, colchicine cross-resistance occurred only in cells that were highly resistant to VCR (.apprxeq. 500-fold). Even at the highest level of VCR resistance (.apprxeq. 600-fold), complete sensitivity to podophyllotoxin was retained. Conversely, cross-resistance to the epipodophyllotoxins, teniposide and etoposide, semisynthetic derivatives of podophyllotoxin, was seen in cells that were > 50-fold resistant to VCR. The same pattern was obtained for the anthracyclines, doxorubicin and daunorubicin. Resistance to low concentrations of VCR apparently does not uniformly confer cross-resistance to other classes of natural product drugs.