We have developed a stable line of the human breast carcinoma cell line MCF-7 by in vitro continuous exposure to increasing concentrations of the antitumoral alkylating agent FCE 24517 (tallimustine). The selected line, MCF-7/24517(1), was resistant to the selecting agent (RI=10) and to a lesser degree to melphalan, MEN 10710 (a related dystamycin analog), doxorubicin and etoposide, but not to m-AMSA. MCF-7/24517(1) cells did not express the multidrug-resistant phenotype, evaluated in terms of mRNA for mdr-1 and gp170 glycoprotein. A significant, albeit modest, increase in the cellular content of glutathione was measured and therefore other resistance mechanism(s) should be operative. We conclude that the MCF-7/24517(1) line is a valuable model to investigate the mechanisms of resistance of FCE 24517 and its derivatives.
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