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Absence of Topoisomerase IIß in an Amsacrine-resistant Human Leukemia Cell Line with Mutant Topoisomerase II¹

University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [C. E. H., L. M. T., L. A. Z.], and Cleveland Clinic, Cleveland, Ohio 44195 [K. A. H., R. G.]

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 II that was thought to explain this resistance. However, our present data show that expression of topo IIß RNA in HL-60/AMSA is only 10% of that in HL-60, and topo IIß protein levels are undetectable. Southern analysis of topo IIß 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 IIß expression may contribute to the intercalator resistance of HL-60/AMSA cells.

¹ Supported by NIH Grants CA40900 (to L. A. Z.) and CA35531 (to R. G.).

² To whom requests for reprints should be addressed, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Pediatrics, Box 87, Houston, TX 77030. Phone: (713) 745-0157; Fax: (713) 794-5531; E-mail: cherzog@notes.mdacc.tmc.edu.

Received 9/ 3/98. Accepted 10/16/98.

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