Absence of Topoisomerase IIßin an Amsacrine-resistant Human Leukemia Cell Line with Mutant Topoisomerase Ha1

Numerous chemotherapeutic agents act via stabilization of a topoisomerase (topo) II-DNA complex. HL-60/AMSA, a human leukemia cell line, is resistant to intercalator-mediated DNA complex formation and cytotoxicity. HL-60/AMSA contains a mutant form of topo Ila that was thought to explain this resistance. However, our present data show that expression of topo II/¡RNA in HL-60/AMSA is only 10% ofthat in HI.-60, and topo 11/i protein levels are undetectable. Southern analysis of topo 11ß shows no differences in gene dosage between the two cell lines but does show differences in the restriction patterns. These data suggest that decreased topo Ilßexpression may contribute to the intercalator resist ance of HL-60/AMSA cells.

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