Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1983 Nov;72(5):1844–1850. doi: 10.1172/JCI111145

Bromodeoxyuridine in tumors and chromosomes detected with a monoclonal antibody.

G Morstyn, S M Hsu, T Kinsella, H Gratzner, A Russo, J B Mitchell
PMCID: PMC370474  PMID: 6355188

Abstract

Using a monoclonal antibody to bromodeoxyuridine (BUdR) and immunohistochemistry, we measured the incorporation of this thymidine analogue into the DNA of human normal and malignant cells exposed in vivo. BUdR given as a constant intravenous infusion for 12 or 24 h daily for up to 13 d resulted in a steady-state plasma level of 10(-6) M during the infusion. We demonstrated extensive incorporation of BUdR into both normal skin, normal bone marrow, and malignant melanoma cells. In addition, this infusion of BUdR was adequate to identify sister chromatid exchanges from human marrow chromosomes exposed in vivo. Using this constant infusion, significant but reversible (acute) toxicity was observed with myelosuppression and skin photosensitivity. These techniques, which are considerably less cumbersome and time-consuming than the use of radioactive isotopes of thymidine, can be used for further human studies of cell kinetics and chromosomal replication in both normal and malignant cells.

Full text

PDF
1844

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allen J. W., Latt S. A. Analysis of sister chromatid exchange formation in vivo in mouse spermatogonia as a new test system for environmental mutagens. Nature. 1976 Apr 1;260(5550):449–451. doi: 10.1038/260449a0. [DOI] [PubMed] [Google Scholar]
  2. Bagshaw M. A., Doggett R. L., Smith K. C., Kaplan H. S., Nelsen T. S. Intra-arterial 5-bromodeoxyuridine and x-ray therapy. Am J Roentgenol Radium Ther Nucl Med. 1967 Apr;99(4):886–894. doi: 10.2214/ajr.99.4.886. [DOI] [PubMed] [Google Scholar]
  3. Barrett J. C., Tsutsui T., Ts'o P. O. Neoplastic transformation induced by a direct perturbation of DNA. Nature. 1978 Jul 20;274(5668):229–232. doi: 10.1038/274229a0. [DOI] [PubMed] [Google Scholar]
  4. Goto K., Maeda S., Kano Y., Sugiyama T. Factors involved in differential Giemsa-staining of sister chromatids. Chromosoma. 1978 May 16;66(4):351–359. doi: 10.1007/BF00328535. [DOI] [PubMed] [Google Scholar]
  5. Gratzner H. G. Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: A new reagent for detection of DNA replication. Science. 1982 Oct 29;218(4571):474–475. doi: 10.1126/science.7123245. [DOI] [PubMed] [Google Scholar]
  6. Hagan M. P., Elkind M. M. Changes in repair competency after 5-bromodeoxyuridine pulse labeling and near-ultraviolet light. Biophys J. 1979 Jul;27(1):75–85. doi: 10.1016/S0006-3495(79)85203-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hsu S. M., Cossman J., Jaffe E. S. Lymphocyte subsets in normal human lymphoid tissues. Am J Clin Pathol. 1983 Jul;80(1):21–30. doi: 10.1093/ajcp/80.1.21. [DOI] [PubMed] [Google Scholar]
  8. Hutchinson F. The lesions produced by ultraviolet light in DNA containing 5-bromouracil. Q Rev Biophys. 1973 May;6(2):201–246. doi: 10.1017/s0033583500001141. [DOI] [PubMed] [Google Scholar]
  9. LITTLEFIELD J. W., GOULD E. A. The toxic effect of 5-bromodeoxyuridine on cultured epithelial cells. J Biol Chem. 1960 Apr;235:1129–1133. [PubMed] [Google Scholar]
  10. Latt S. A. Microfluorometric detection of deoxyribonucleic acid replication in human metaphase chromosomes. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3395–3399. doi: 10.1073/pnas.70.12.3395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mitchell J. B., Kinsella T. J., Russo A., McPherson S., Rowland J., Smith B. H., Kornblith P. L., Glatstein E. Radiosensitization of hematopoietic precursor cells (CFUc) in glioblastoma patients receiving intermittent intravenous infusions of bromodeoxyuridine (BUdR). Int J Radiat Oncol Biol Phys. 1983 Apr;9(4):457–463. doi: 10.1016/0360-3016(83)90061-5. [DOI] [PubMed] [Google Scholar]
  12. Perry P., Evans H. J. Cytological detection of mutagen-carcinogen exposure by sister chromatid exchange. Nature. 1975 Nov 13;258(5531):121–125. doi: 10.1038/258121a0. [DOI] [PubMed] [Google Scholar]
  13. Shirakawa S., Luce J. K., Tannock I., Frei E., 3rd Cell proliferation in human melanoma. J Clin Invest. 1970 Jun;49(6):1188–1199. doi: 10.1172/JCI106333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Szybalski W. X-ray sensitization by halopyrimidines. Cancer Chemother Rep. 1974 Jul-Aug;58(4):539–557. [PubMed] [Google Scholar]
  15. Vogel W., Bauknecht T. Differential chromatid staining by in vivo treatment as a mutagenicity test system. Nature. 1976 Apr 1;260(5550):448–449. doi: 10.1038/260448a0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES