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The Johns Hopkins Oncology Center, Baltimore, Maryland 21205
Taxol, a diterpenoid plant product that enhances the polymerization of tubulin, is currently entering clinical trials in the treatment of human leukemia. In order to develop an in vitro assay to predict tumor sensitivity to taxol, human leukemic cell lines were exposed to clinically achievable concentrations of taxol for relevant exposure periods. Changes in microtubules visualized by indirect immunofluorescence were compared to drug sensitivity measured by a clonogenic assay. Taxol produced either multiple mitotic asters in G2/M or microtubule bundling throughout the cell cycle. In cells that were relatively resistant to taxol, microtubule bundling was reversible while microtubule bundling in relatively sensitive cells persisted in the presence or absence of taxol. In contrast, aster formation was unrelated to cytotoxicity in any cell line. In the future, these microtubule effects may be useful in predicting the chemotherapeutic efficacy of taxol.
1 Supported in part by NIH Grant CA-34472, National Cancer Institute Grant 2-P30-CA06973-24, American Cancer Society Grant CH-369, and National Cancer Institute Contract NCI-CM-57738. Presented in part at the annual meeting of the American Association for Cancer Research, Los Angeles, California, May, 1986.
2 Recipient of an American Cancer Society Career Development Award. To whom requests for reprints should be addressed, at The Johns Hopkins Oncology Center, Pharmacology Laboratory, Room 1-121, 600 North Wolfe Street, Baltimore, MD 21205.
Received 11/19/87. Revised 3/23/88. Accepted 4/11/88.
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