This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lawrence, T. S. Articles by Ensminger, W. D. Search for Related Content PubMed PubMed Citation Articles by Lawrence, T. S. Articles by Ensminger, W. D.

The Potential Superiority of Bromodeoxyuridine to Iododeoxyuridine as a Radiation Sensitizer in the Treatment of Colorectal Cancer¹

Departments of Radiation Oncology [T. S. L., M. A. D.], Pharmacology [J. M., P. L. S., W. D. E.], Pathology [S. K. M., P. E. M.], Biostatistics [D. P. N.], and Internal Medicine [W. D. E.], University of Michigan Medical Center, Ann Arbor, Michigan 48109

Although the thymidine analogues 5-bromo-2'-deoxyuridine (BrdUrd) and 5-iodo-2'-deoxyuridine (IdUrd) have been used successfully as radiation sensitizers in clinical trials, it is not clear which of these agents is the more promising to pursue. To begin to assess this question with regard to colorectal cancer metastatic to the liver, a study was carried out using HT29 human colon cancer cells in culture and implanted in nude mice as xenografts. Cells and animals were treated with BrdUrd ± the thymidylate synthase inhibitor 5-fluoro-2'-deoxyuridine (FdUrd), and the results compared to our previous studies with IdUrd ± FdUrd (T. S. Lawrence, M. A. Davis, P. E. McKeever, J. Maybaum, P. L. Stetson, D. P. Normolle, and W. D. Ensminger. Cancer Res., 51: 3900–3905, 1991). Using cultured cells, it was found that FdUrd (at concentrations of 10 nM) increased: (a) the incorporation of BrdUrd into the DNA of cultured tumor cells; (b) BrdUrd-mediated radiosensitization; (c) BrdUrd-mediated increase in radiation-induced DNA damage; and (d) BrdUrd-mediated decrease in the repair of radiation-induced damage. The incorporation of BrdUrd was greater than or equal to the incorporation of IdUrd previously determined under the same exposure conditions. Studies using nude mice bearing HT29 xenografts showed that FdUrd increased BrdUrd incorporation more into tumors than into the normal liver. Most tumor cells incorporated BrdUrd (labeling index after a 4-day infusion = 87 ± 2%; SE); in the liver, labeling was confined chiefly to nonparenchymal cells. In both the presence and absence of FdUrd, the incorporation of BrdUrd into tumors was significantly and consistently greater than the incorporation of IdUrd measured under the same conditions of drug administration (by a factor of 1.2–3.6). Furthermore, the administration of BrdUrd ± FdUrd tended to produce less weight loss and hematological toxicity than IdUrd ± FdUrd. These findings suggest that BrdUrd may be superior to IdUrd as a radiation sensitizer in the treatment of colorectal cancer metastatic to the liver.

¹ This work was presented in part at the 9th International Conference for Radiation Research in Toronto, Canada (July, 1991) and was supported by NIH Grants CA 53440, CA 44173, and CA 42761. T. S. L. is a recipient of an American Cancer Society Career Development Award (91–210).

² To whom requests for reprints should be addressed, at Department of Radiation Oncology, University of Michigan Medical Center, 1331 East Ann Street, Ann Arbor, MI 48109-0582.

Received 10/ 4/91. Accepted 4/21/92.

This article has been cited by other articles:

				M. A. Morgan, L. A. Parsels, J. D. Parsels, A. K. Mesiwala, J. Maybaum, and T. S. Lawrence Role of Checkpoint Kinase 1 in Preventing Premature Mitosis in Response to Gemcitabine Cancer Res., August 1, 2005; 65(15): 6835 - 6842. [Abstract] [Full Text] [PDF]

				T. S. Lawrence, M. A. Davis, A. Hough, and A. Rehemtulla The Role of Apoptosis in 2',2'-Difluoro-2'-deoxycytidine (Gemcitabine)-mediated Radiosensitization Clin. Cancer Res., February 1, 2001; 7(2): 314 - 319. [Abstract] [Full Text]

				E. Kievit, M. K. Nyati, E. Ng, L. D. Stegman, J. Parsels, B. D. Ross, A. Rehemtulla, and T. S. Lawrence Yeast Cytosine Deaminase Improves Radiosensitization and Bystander Effect by 5-Fluorocytosine of Human Colorectal Cancer Xenografts Cancer Res., December 1, 2000; 60(23): 6649 - 6655. [Abstract] [Full Text]

				L. D. Stegman, A. Rehemtulla, B. Beattie, E. Kievit, T. S. Lawrence, R. G. Blasberg, J. G. Tjuvajev, and B. D. Ross Noninvasive quantitation of cytosine deaminase transgene expression in human tumor xenografts with in vivo magnetic resonance spectroscopy PNAS, August 17, 1999; 96(17): 9821 - 9826. [Abstract] [Full Text] [PDF]

				A. Eisbruch, J. M. Robertson, C. M. Johnston, J. Tworek, K. R. Reynolds, J. A. Roberts, and T. S. Lawrence Bromodeoxyuridine Alternating With Radiation for Advanced Uterine Cervix Cancer: A Phase I and Drug Incorporation Study J. Clin. Oncol., January 1, 1999; 17(1): 31 - 31. [Abstract] [Full Text] [PDF]