Two multi-drug resistant variants of the human carcinoma line Hep-2 have been selected by adaptation to progressively increasing concentrations of adriamycin. In comparison to the wild-type Hep-2 cells, the variant lines both showed approximately 100-fold resistance to adriamycin, 10 to 20-fold resistance to the vinca alkaloids but only 2-3 fold resistance to VP-16 and VM-26. There was essentially no difference between wild-type and variant cells in regard to sensitivity to threosulfan and 5-fluorouracil. The drug-resistant phenotype is stable for at least 3 months in the absence of drug, and is partially reversible by concomitant treatment with Verapamil. Chromosomal abnormalities consistent with gene amplification were observed in one of the variant lines. Sensitivity of variant cells to adriamycin was enhanced following trypsin-EDTA treatment.
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