MULTIDRUG-RESISTANCE IN LEUKEMIC-CELL LINE K562 A02 INDUCED BY DOXORUBICIN/

AIM: To study the mechanism of the development of multidrug resistance in leukemic cells. METHODS: A human leukemic cell line K562/A02 was e stablished by stepwise increase of concentrations of doxorubicin (Dox) in medium. P-glycoprotein was detected by immunohistochemistry assay. The mdr1 gene expression was measured by RT-PCR. The amplification of mdr1 gene in its genome, and DNA topisomerase II (Top II) gene expres sion were determined by dot-blot hybridization. RESULTS: K562/A02 was highly cross-resistant to vincristine (VCR), homoharringtonin (HHT), a msacrine (m-AMSA), daunorubicin (Dau) and etoposide (VP-16), slightly to cytosine arabinoside (Ara-C), but not cisplatin (Cis), methotrexate (MTX) and fluorouracil (5-FU), showing a typical phenotype of MDR. In tracellular accumulation of Dau in K562/A02 was 33 % as high as that i n K562. P-glycoprotein P-170 was positive. In K562/A02, the mdr1 gene did not amplify, the mdr1 mRNA level was markedly higher, the Top II m RNA level was lower, and glutathione-S-transferase (GST) activity was higher than in K562. CONCLUSION: mdr1 mRNA was overexpression and thus the encoded P-170 was responsible for MDR in K562/A02 while Top II or GST may play a role in MDR.