Prevention of adriamycin-induced mdrl gene amplification and expression PDF Print E-mail
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Prevention of adriamycin-induced mdrl gene amplification and expression
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Prevention of adriamycin-induced mdrl gene amplification and expression in mouse leukemia cells by simultaneous treatment with the anti-recombinogen bromovinyldeoxyuridine

Authors: Fahrig R.; Steinkamp-Zucht A.; Schaefer A.1

RESprotect GmbH - Prevention of Chemoresistance, Fiedlerstraße 34, D-01307 Dresden and 1Fraunhofer Arbeitsgruppe für Toxikologie und Umweltmedizin, Hamburg/Germany

 

Summary

 

The anti-recombinogenic substance (E)-5-(2-bromovinyl)-2prime-deoxyuridine (BVDU) was tested for its ability to prevent adriamycin-induced mdrl gene amplification and expression in mouse leukemia cells in vitro. F4-6 cells that were treated with stepwise enhanced doses of adriamycin acquired resistance against adriamycin. While 20 ng/ml adriamycin showed strong toxic effects in sensitive cells, the same dose was tolerated at the end of the long-term experiment following treatment with stepwise enhanced doses of adriamycin. In parallel experiments, 0.5 or 1 mgrg/ml BVDU was given together with adriamycin. BVDU prevented the formation of resistance against adriamycin treatment. Using differential PCR, the signal intensity of the mdrla-specific band appeared markedly increased in adriamycin-resistant cells, while the signal intensities of the adriamycin + BVDU-treated cells resembled the intensity ratio of the untreated control cells. Beyond that, in resistant F4-6 cells increased expression of mdr genes was demonstrated by Northern blot analysis.

 

Key words

gene amplification/leukemia/mouse cells/multidrug resistance/recombination