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Chemotherapy of malignant tumors is ineffective usually because of tumor cell resistance to it. Two types of resistance are known: cell resistance to a certain drug and multiple drug resistance (MDR). MDR covers a wide spectrum of drugs with different chemical structure and mechanisms of action. The most frequent cause of MDR is hyperexpression in the plasma membrane of P glycoprotein cells, which is coded for by MDR1 gene realizing active release of many cytotoxic substances from cells (Pgp-MDR). Acquisition of MDR phenotype by patient's cells impedes therapy and is often a poor prognostic sign, and therefore testing of material from cancer patients for MDR phenotype is important for selecting tumor therapy. We adapted the reverse transcriptase polymerase chain reaction (RT-PCR) to evaluating the MDR1 gene expression in peripheral blood cells of patients with hemoblastosis, assessed its sensitivity and specificity, and carried out clinical trials with blood samples from patients with MDR. Comparison of the results of RT-PCR with the findings of other methods used for detection of Pg-MDR showed their good correlation in the majority of cases. These results recommend these method for clinical practice in patients with hemoblastosis.

mdr-Transfected K-562 cells revealed a relatively high resistance to cytotoxic monokines and ionizing radiation as compared to parental cells. Taken together with what is known about the resistance of mdr-expressing cells to multiple cytotoxic drugs, our results point to malignant cells having universal mechanisms of chemo-, bio- and radioresistance.

Three independent subclones (B2, B3 and C9) of human myelogenous leukemia cell line K562 selected with adriamycin (ADM) were analysed. Cross-resistance of these ADM-resistant cells was examined for a resistance to the number of drugs including colchicine, actinomycin D and ethidium bromide. MDR 1 gene amplification in B3 and C9 subclones was detected using Southern-hybridization with specific probe. Additional genetical material was found in genomes of resistant cells by analysis of G-banded metaphase chromosomes. An extraordinarily long marker chromosome was observed in every C9 metaphase plate. The character of this chromosome G-banding suggests that it may be a derivative of chromosome 5 containing a large homogeneously staining region (HSR) in locus 5q15. Both B2 and B3 subclones expressed double minute chromosomes (DMs) in 5% of cells. In the course of a prolonged cultivation (about 2 years) of C9 cells in the presence of ADM a progressive karyotype destabilization was observed: the frequency of new markers formation in C9 cells increased, cells having additional copies of marker chromosome with HSR appeared, the length of HSR varied, coexistence of HSR and DMs being found in several C9 cells. These karyotypical changes may be regarded as patterns of genome destabilization due to the multidrug resistance of K562/ADM cells.