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Dynamics of Bromodeoxyuridine Incorporation into DNA of Squamous Carcinoma Cells During Mid and Late Logarithmic Growth

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Abstract

Head and neck squamous carcinoma cell lines, UM-SCC 1, 5, 9, 11B, and 14B, were exposed in vitro to bromodeoxyuridine (BUdR) during logarithmic growth to determine the effects of drug concentration (0.01 to 10 µM) and duration of exposure (3, 7, and 10 days) on cell growth and on incorporation of BUdR into DNA. Concentrations of less than 1.0 µM were not growth inhibitory except with UM-SCC-11B. After 10 days of exposure to 5 µM BUdR, survival fractions for all lines ranged from 2 to 65% of controls. Replacement of thymidine by BUdR in DNA was assessed by gas chromatography/mass spectroscopy. Percentage replacement (% R) was described by the equation % R = 100 (C/t)s/[(C/t)50 s + (C/t)s], where C is the concentration of BUdR (µM), t is the time in days, s is a constant, and (C/t)50 is a constant corresponding to % R = 50%. BUdR incorporation reached a time-and concentration-dependent maximum that, after 3 to 7 days of culture in 10 µM BUdR, ranged from 30 to 60% R. Subsequently, % R declined with time even though the cells were fed daily with fresh BUdR-containing medium.

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Authors and Affiliations

  1. The University of Michigan Medical School, Ann Arbor, Michigan, 48109

    Amnon Shapira & Thomas E. Carey

  2. Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, Michigan, 48109

    John G. Wagner, Jonathan Maybaum, Phillip L. Stetson & William D. Ensminger

  3. College of Pharmacy, The University of Michigan Medical School, Ann Arbor, Michigan, 48109

    John G. Wagner

  4. Upjohn Center for Clinical Pharmacology, The University of Michigan Medical School, Ann Arbor, Michigan, 48109

    John G. Wagner, John G. Wagner, Ira S. Wollner, Jonathan Maybaum, Phillip L. Stetson & William D. Ensminger

  5. Department of Internal Medicine, The University of Michigan Medical School, Ann Arbor, Michigan, 48109

    Ira S. Wollner & William D. Ensminger

  6. Department of Otolaryngology, Barzilai Medical Center, Ashkelov, 73606, Israel

    Amnon Shapira

  7. Cancer Research Laboratory, 6020 KHRI, The University of Michigan, Box 0506, 1301 East Ann Street, Ann Arbor, Michigan, 48109-0506

    Thomas E. Carey

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  1. Amnon Shapira
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  2. John G. Wagner
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  3. Ira S. Wollner
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  4. Jonathan Maybaum
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  5. Phillip L. Stetson
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  6. William D. Ensminger
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  7. Thomas E. Carey
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Shapira, A., Wagner, J.G., Wollner, I.S. et al. Dynamics of Bromodeoxyuridine Incorporation into DNA of Squamous Carcinoma Cells During Mid and Late Logarithmic Growth. Pharm Res 5, 518–522 (1988). https://doi.org/10.1023/A:1015925509778

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  • DOI: https://doi.org/10.1023/A:1015925509778

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