Novel nucleolar and nuclear morphology in a vincristine-dependent human leukemia cell line (L100)

Acquired resistance to chemotherapeutic drugs by tumor cells is an important obstacle to effective therapy of human malignancy. We now describe a vincristine (VCR)-induced multidrug-resistant (MDR) human acute lymphatic leukemia cell line, the sustained in vitro growth of which is dependent on vincristine. The doubling time for parental drug-sensitive cells (L0) is 40.2 +/- 13.2 h and for the MDR subline (L100) 62.5 +/- 11.3 h. L100 cells have similar G2 and mitotic phase to parental cells, express the MDR phenotype, and are characterized by novel morphologic features with multilobulated nuclei and multiple small nucleoli. Compared with L0 cells which have 2-3 nucleoli per cell, L100 cells have 7-8 nucleoli per cell. Average nucleolar area is 11.3 +/- 7.3 microns 2 for L0 and 2.5 +/- 2.4 microns 2 for L100 cells determined by the laser scanning method. The striking morphologic abnormalities of L100 cells suggest a drug-induced cytoskeletal abnormality. The relationship of these abnormalities to the VCR growth dependence of L100 cells is discussed.