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Mitomycin C cross-resistance induced by Adriamycin in human ovarian cancer cells in vitro

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Summary

We prepared Adriamycin-resistant cancer cells by exposing an ovarian serous cystadenocarcinoma cell line to the drug. The resistant cells also showed cross-resistance to a wide variety of other compounds, including vincristine, vinblastine, actinomycin D, daunorubicin, mitomycin C and carboquone. Against vincristine, the cells showed a >5,000-fold increase in resistance, far surpassing their resistance to the selection drug. The resistant cells displayed a decrease in intracellular Adriamycin content and an increase in the mRNA of themdr-1 gene coding for P-glycoprotein, with no amplification of the DNA. In revertant cells, resistance to Adriamycin was lost, but that to mitomycin C was maintained. Adriamycin resistance was partially overcome by the addition of verapamil or cyclosporin A, but cross-resistance to mitomycin C was not influenced at all. These results strongly suggest that the resistance to mitomycin C observed in our Adriamycin-resistant cells was due to some other mechanism than that causing multidrug resistance.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, 466, Nagoya, Japan

    Kimio Mizuno, Yoshihito Furuhashi, Osamu Maeda, Mitsumasa Iwata, Toshiya Misawa, Michiyasu Kawai, Takeo Kano & Yutaka Tomoda

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  1. Kimio Mizuno
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  2. Yoshihito Furuhashi
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  3. Osamu Maeda
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  4. Mitsumasa Iwata
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Mizuno, K., Furuhashi, Y., Maeda, O. et al. Mitomycin C cross-resistance induced by Adriamycin in human ovarian cancer cells in vitro. Cancer Chemother Pharmacol 26, 333–339 (1990). https://doi.org/10.1007/BF02897288

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