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Bromodeoxyuridine-mediated radiosensitization in human glioma: the effect of concentration, duration, and fluoropyrimidine modulation.

Publication ,  Journal Article
McLaughlin, PW; Lawrence, TS; Seabury, H; Nguyen, N; Stetson, PL; Greenberg, HS; Mancini, WR
Published in: Int J Radiat Oncol Biol Phys
October 15, 1994

PURPOSE: To define the relative influence of duration of exposure, concentration, and modulation by fluorodeoxyuridines (FdUrd) on the incorporation of 5-bromo-2-deoxyuridine (BrdUrd) into DNA of a human malignant glioma line (D-54) in vitro and in vivo. IN VITRO STUDIES: an established human malignant glioma line (D-54) was exposed to a clinically achievable concentration of BrdUrd to model intravenous (1 microM BrdUrd) and intraarterial (4 microM BrdUrd) conditions. The influence of modulation was assessed using 1 nM FdUrd. Incorporation of BrdUrd, radiosensitization, and cytotoxicity were determined after 24, 72, and 120 h drug exposures. In Vivo studies: nude mice bearing D-54 xenografts were infused with BrdUrd at 100 mg/kg/day for 7 and 14 days or BrdUrd at 400 mg/kg/day for 5 days. The influence of modulation was assessed by combining 100 mg/kg/day of BrdUrd with 0.1, 0.3, and 1 mg/kg/day FdUrd for 7 days. Incorporation of BrdUrd into the DNA of tumor, gut, and marrow were determined. RESULTS: In Vitro: thymidine replacement and radiosensitization were a function of concentration, and incorporation began to plateau after 2 to 3 population doublings. Modulation with 1 nM FdUrd significantly increased incorporation. Radiosensitization was a linear function of thymidine replacement under all conditions tested. In Vivo: infusion with 400 mg/kg/day for 5 days resulted in greater tumor incorporation (10.3 +/- 0.4% thymidine replaced) than treatment with 100 mg/kg/day for 14 days (6.0 +/- 0.6% of thymidine replaced). Infusion of FdUrd with BrdUrd increased normal tissue incorporation of BrdUrd, but failed to increase BrdUrd incorporation in tumor cells. CONCLUSION: These results suggest that relatively short, high dose rate infusions may be preferable to long, low dose rate infusions. The potential benefit of FdUrd modulation demonstrated in vitro may be difficult to realize using continuous systemic infusions.

Duke Scholars

Published In

Int J Radiat Oncol Biol Phys

DOI

ISSN

0360-3016

Publication Date

October 15, 1994

Volume

30

Issue

3

Start / End Page

601 / 607

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Radiation-Sensitizing Agents
  • Oncology & Carcinogenesis
  • Neoplasms, Experimental
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice
  • In Vitro Techniques
  • Humans
 

Citation

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McLaughlin, P. W., Lawrence, T. S., Seabury, H., Nguyen, N., Stetson, P. L., Greenberg, H. S., & Mancini, W. R. (1994). Bromodeoxyuridine-mediated radiosensitization in human glioma: the effect of concentration, duration, and fluoropyrimidine modulation. Int J Radiat Oncol Biol Phys, 30(3), 601–607. https://doi.org/10.1016/0360-3016(92)90946-f
McLaughlin, P. W., T. S. Lawrence, H. Seabury, N. Nguyen, P. L. Stetson, H. S. Greenberg, and W. R. Mancini. “Bromodeoxyuridine-mediated radiosensitization in human glioma: the effect of concentration, duration, and fluoropyrimidine modulation.Int J Radiat Oncol Biol Phys 30, no. 3 (October 15, 1994): 601–7. https://doi.org/10.1016/0360-3016(92)90946-f.
McLaughlin PW, Lawrence TS, Seabury H, Nguyen N, Stetson PL, Greenberg HS, et al. Bromodeoxyuridine-mediated radiosensitization in human glioma: the effect of concentration, duration, and fluoropyrimidine modulation. Int J Radiat Oncol Biol Phys. 1994 Oct 15;30(3):601–7.
McLaughlin, P. W., et al. “Bromodeoxyuridine-mediated radiosensitization in human glioma: the effect of concentration, duration, and fluoropyrimidine modulation.Int J Radiat Oncol Biol Phys, vol. 30, no. 3, Oct. 1994, pp. 601–07. Pubmed, doi:10.1016/0360-3016(92)90946-f.
McLaughlin PW, Lawrence TS, Seabury H, Nguyen N, Stetson PL, Greenberg HS, Mancini WR. Bromodeoxyuridine-mediated radiosensitization in human glioma: the effect of concentration, duration, and fluoropyrimidine modulation. Int J Radiat Oncol Biol Phys. 1994 Oct 15;30(3):601–607.
Journal cover image

Published In

Int J Radiat Oncol Biol Phys

DOI

ISSN

0360-3016

Publication Date

October 15, 1994

Volume

30

Issue

3

Start / End Page

601 / 607

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Radiation-Sensitizing Agents
  • Oncology & Carcinogenesis
  • Neoplasms, Experimental
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice
  • In Vitro Techniques
  • Humans