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. 1960 Feb 1;7(1):61–71. doi: 10.1083/jcb.7.1.61

Effects of 5-Fluorodeoxyuridine and Related Halogenated Pyrimidines on the Sand-Dollar Embryo

David A Karnofsky 1, Ross S Basch 1
PMCID: PMC2224848  PMID: 14404541

Abstract

The embryo of the sand-dollar (Echinarachnius parma) was exposed to various concentrations of fluorinated pyrimidines immediately after fertilization. FUDR (5-fluorodeoxyuridine) was most active, and a concentration of 2 to 4 mγ/10 cc. (0.8 to 1.6 x 10-6 m.eq./liter) blocked development at the early blastula stage. Larger doses interrupted development at the same stage. This effect was prevented by thymidine (TDR) and thymine (T); and these pyrimidines protected against many times the minimal lethal concentration of FUDR. TDR was active as a protective agent if added just before early blastula formation. The other fluorinated pyrimidines, 5-fluorouracil (FU), 5-fluorouridine (FUR), 5-fluorocytidine (FCR), 5-fluorodeoxycytidine (FCDR), and 5-fluoroorotic acid (FO), were also studied. These drugs produced effects on embryonic development similar to those seen with FUDR. The effective concentrations, however, varied greatly. T and TDR provided protection against these drugs, but in most cases they were not so effective as against FUDR. 5-Bromodeoxyurdine (BrUDR), beginning at the early blastula stage, caused a random pattern of embryonic death up to the pluteus stage. This drug has been shown to be incorporated into bacterial DNA. BrUDR protected embryos against the early lethal effects of FUDR presumably acting as a thymidine substitute, but the embryos died subsequently in a pattern similar to that seen with BrUDR alone. FUDR and BrUDR appear to inhibit the formation and alter the structure of DNA, respectively, distinctive effects whch may provide a means for studying the role of DNA in embryonic development.

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Selected References

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

  1. BIEBER S., SPENCE J. A., HITCHINGS G. H. Nucleic acids and their derivatives and the development of Rana pipiens. I. Oögenesis. Exp Cell Res. 1959 Jan;16(1):202–214. doi: 10.1016/0014-4827(59)90207-1. [DOI] [PubMed] [Google Scholar]
  2. BOSCH L., HARBERS E., HEIDELBERGER C. Studies on fluorinated pyrimidines. V. Effects on nucleic acid metabolism in vitro. Cancer Res. 1958 Apr;18(3):335–343. [PubMed] [Google Scholar]
  3. CHAUDHURI N. K., MONTAG B. J., HEIDELBERGER C. Studies on fluorinated pyrimidines. III. The metabolism of 5-fluorouracil-2-C14 and 5-fluoroorotic-2-C14 acid in vivo. Cancer Res. 1958 Apr;18(3):318–328. [PubMed] [Google Scholar]
  4. DANNEBERG P. B., MONTAG B. J., HEIDELBERGER C. Studies on fluorinated pyrimidines. IV. Effects on nucleic acid metabolism in vivo. Cancer Res. 1958 Apr;18(3):329–334. [PubMed] [Google Scholar]
  5. DUNN D. B., SMITH J. D., ZAMENHOF S., GRIBOFF G. Incorporation of halogenated pyrimidines into the deoxyribonucleic acids of Bacterium coli and its bacteriophages. Nature. 1954 Aug 14;174(4424):305–307. [PubMed] [Google Scholar]
  6. EIDINOFF M. L., KNOLL J. E., KLEIN D. Effect of 5-fluorouracil on the incorporation of precursors into nucleic acid pyrimidines. Arch Biochem Biophys. 1957 Sep;71(1):274–275. doi: 10.1016/0003-9861(57)90028-0. [DOI] [PubMed] [Google Scholar]
  7. ELSON D., GUSTAFSON T., CHARGAFF E. The nucleic acids of the sea-urchin during embryonic development. J Biol Chem. 1954 Jul;209(1):285–294. [PubMed] [Google Scholar]
  8. HEIDELBERGER C., CHAUDHURI N. K., DANNEBERG P., MOOREN D., GRIESBACH L., DUSCHINSKY R., SCHNITZER R. J., PLEVEN E., SCHEINER J. Fluorinated pyrimidines, a new class of tumour-inhibitory compounds. Nature. 1957 Mar 30;179(4561):663–666. doi: 10.1038/179663a0. [DOI] [PubMed] [Google Scholar]
  9. HEIDELBERGER C., GRIESBACH L., CRUZ O., SCHNITZER R. J., GRUNBERG E. Fluorinated pyrimidines. VI. Effects of 5-fluorouridine and 5-fluoro-2'-deoxyuridine on transplanted tumors. Proc Soc Exp Biol Med. 1958 Feb;97(2):470–475. doi: 10.3181/00379727-97-23777. [DOI] [PubMed] [Google Scholar]
  10. HEIDELBERGER C., GRIESBACH L., MONTAG B. J., MOOREN D., CRUZ O., SCHNITZER R. J., GRUNBERG E. Studies on fluorinated pyrimidines. II. Effects on transplanted tumors. Cancer Res. 1958 Apr;18(3):305–317. [PubMed] [Google Scholar]
  11. HITCHINGS G. H., ELION G. B., FALCO E. A. Antagonists of nucleic acid derivatives. II. Reversal studies with substances structurally related to thymine. J Biol Chem. 1950 Aug;185(2):643–649. [PubMed] [Google Scholar]
  12. HITCHINGS G. H., ELION G. B., FALCO E. A., RUSSELL P. B., VANDERWERFF H. Studies on analogs of purines and pyrimidines. Ann N Y Acad Sci. 1950 Jul 7;52(8):1318–1335. doi: 10.1111/j.1749-6632.1950.tb54032.x. [DOI] [PubMed] [Google Scholar]
  13. HOFF-JORGENSEN E., ZEUTHEN E. Evidence of cytoplasmic deoxyribosides in the frog's egg. Nature. 1952 Feb 9;169(4293):245–246. doi: 10.1038/169245a0. [DOI] [PubMed] [Google Scholar]
  14. KARNOFSKY D. A., BEVELANDER G. Effects on DON (6-diazo-5-oxo-L-norleucine) and azaserine on the sand-dollar embryo. Proc Soc Exp Biol Med. 1958 Jan;97(1):32–37. doi: 10.3181/00379727-97-23639. [DOI] [PubMed] [Google Scholar]
  15. LEVENBERG B., MELNICK I., BUCHANAN J. M. Biosynthesis of the purines. XV. The effect of aza-L-serine and 6-diazo-5-oxo-L-norleucine on inosinic acid biosynthesis de novo. J Biol Chem. 1957 Mar;225(1):163–176. [PubMed] [Google Scholar]
  16. MATTHEWS R. E. Biosynthetic incorporation of metabolite analogues. Pharmacol Rev. 1958 Sep;10(3):359–406. [PubMed] [Google Scholar]
  17. RICH M. A., BOLAFFI J. L., KNOLL J. E., CHEONG L., EIDINOFF M. L. Growth inhibition of a human tumor cell strain by 5-fluorouracil, 5-fluorouridine, and 5-fluoro-2'-deoxyuridine; reversal studies. Cancer Res. 1958 Jul;18(6):730–735. [PubMed] [Google Scholar]

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