The role of reduced growth rate in the development of drug resistance of HOB1 lymphoma cells to vincristine.

An MDR cell line resistant to 1.0 microM vincristine (designated HOB1/VCR1.0) was established. The growth rate of HOB1/VCR1.0 cells was slow. The cells did not go into active proliferation although the drug treatment was released for two months (revertant cells). The HOB1/VCR1.0 cell line and its revertant were resistant to a high dose of vincristine (up to 20 microM). These two cell lines showed a decrease in expression of the hyperphosphorylated form of the retinoblastoma protein, of which the hypophosphorylated form has been considered to be a tumor suppressor. Similar phenomena were observed in the parental cells surviving brief treatment with a lethal dose of vincristine (0.05 microM). The current study gives the impression that self-inhibited growth rate may participate in the initial drug resistance before the expression of P-glycoprotein when tumor cells are suddenly exposed to chemotherapeutic agents.