Expressions of resistance and cross-resistance in teniposide-resistant L1210 cells.

Resistance to teniposide (VM-26) by VM-26 selected resistant L1210 cells in culture was attributed to alterations in the flux of VM-26 across the plasma membrane and to functions of homogeneously staining regions that appeared on one or more chromosomes. In the present study, electrophoresis of membrane-cytosol fractions of these resistant sublines demonstrated a protein band, Mr 22 kd, that was not evident in similar fractions of drug-sensitive L1210 cells or three revertant sublines. The distribution of this protein among various cellular fractions could be altered by manipulation of the concentration of calcium ions. A representative subline, LIa5 microM, was observed to have vesicles that reacted with Sudan black B stain, an indication of altered lipid metabolism. The LIa5 microM subline was cross-resistant to etoposide, vincristine, doxorubicin, amsacrine, and actinomycin D. Concentrations of VM-26 that inhibited cell division to the same extent caused an accumulation of fewer cells in the G2 stage of cell division in LIa5 microM cultures than in L1210 cultures. These observations indicate that the LIa5 microM subline expressed multiple drug resistance, as well as changes in the expression of cytotoxicity to VM-26.