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. 1978 May;126(Pt 1):37–49.

The teratogenic effects of 5-fluoro-2-desoxyuridine (F.U.D.R.) on the Wistar rat fetus with particular reference to cleft palate.

M W Ferguson
PMCID: PMC1235710  PMID: 148445

Abstract

The teratogenic effects of 5-fluoro-2-desoxyuridine on Wistar rat fetuses were studied macroscopically, microscopically and ultrastructurally. In no case did palatal shelf elevation occur, and a palatal shelf elevating force could not be demonstrated in freshly-removed fetuses. The shelves, like the connective tissues generally, showed clear evidence of depressed mucopolysaccharide synthesis. The shelves eventually ossified in the vertical position, and in some cases their free edges fused with the lateral wall of the oral cavity (palato-oral fusion). The results were consistent with the mucopolysaccharide-turgor hypothesis advanced by the author in a previous paper to account for normal shelf elevation. Phocomelia, brain and limb bud haemorrhages, gross subcutaneous oedema, hyperextension of the cranial base, fused vertebrae, detached epithelia, bizarre brain abnormalities (including some remarkable attempts at neural reconstitution) and growth and ossification of the mandible in the virtual absence of Meckel's cartilages were also noted in these fetuses.

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Selected References

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

  1. ASLING C. W., NELSON M. M., DOUGHERTY H. D., WRIGHT H. V., EVANS H. M. The development of cleft palate resulting from maternal pteroylglutamic (folic) acid deficiency during the latter half of gestation in rats. Surg Gynecol Obstet. 1960 Jul;111:19–28. [PubMed] [Google Scholar]
  2. Bro-Rasmussen F., Jensen B., Hansen O. M., Ostergaard A. H. Fluorodeoxyuridine-induced malformations in mice. Studies on the early stages of teratogenesis. Acta Pathol Microbiol Scand A. 1971;79(1):55–60. [PubMed] [Google Scholar]
  3. DEMYER W., ZEMAN W., PALMER C. G. THE FACE PREDICTS THE BRAIN: DIAGNOSTIC SIGNIFICANCE OF MEDIAN FACIAL ANOMALIES FOR HOLOPROSENCEPHALY (ARHINENCEPHALY). Pediatrics. 1964 Aug;34:256–263. [PubMed] [Google Scholar]
  4. Ferguson M. W. Palatal shelf elevation in the Wistar rat fetus. J Anat. 1978 Mar;125(Pt 3):555–577. [PMC free article] [PubMed] [Google Scholar]
  5. Fogh-Andersen P. Epidemiology and etiology of clefts. Birth Defects Orig Artic Ser. 1971 Jun;7(7):50–53. [PubMed] [Google Scholar]
  6. Frommer J., Margolies M. R. Contribution of Meckel's cartilage to ossification of the mandible in mice. J Dent Res. 1971 Sep-Oct;50(5):1260–1267. doi: 10.1177/00220345710500052801. [DOI] [PubMed] [Google Scholar]
  7. Gorlin R. J., Cervenka J., Pruzansky S. Facial clefting and its syndromes. Birth Defects Orig Artic Ser. 1971 Jun;7(7):3–49. [PubMed] [Google Scholar]
  8. Gorlin R. J., Cervenka J. Syndromes of facial clefting. Scand J Plast Reconstr Surg. 1974;8(1-2):13–25. doi: 10.3109/02844317409084366. [DOI] [PubMed] [Google Scholar]
  9. Greene R. M., Kochhar D. M. Some aspects of corticosteroid-induced cleft palate: a review. Teratology. 1975 Feb;11(1):47–55. doi: 10.1002/tera.1420110106. [DOI] [PubMed] [Google Scholar]
  10. HARTMANN K. U., HEIDELBERGER C. Studies on fluorinated pyrimidines. XIII. Inhibition of thymidylate synthetase. J Biol Chem. 1961 Nov;236:3006–3013. [PubMed] [Google Scholar]
  11. HAYWARD J. R., AVERY J. K. A variation in cleft palate. J Oral Surg (Chic) 1957 Oct;15(4):320–324. [PubMed] [Google Scholar]
  12. Humphrey T. Palatopharyngeal fusion in a human fetus and its relation to cleft palate formation. Ala J Med Sci. 1970 Oct;7(4):398–426. [PubMed] [Google Scholar]
  13. KING C. T., WEAVER S. A., NARROD S. A. ANTIHISTAMINES AND TERATOGENICITY IN THE RAT. J Pharmacol Exp Ther. 1965 Mar;147:391–398. [PubMed] [Google Scholar]
  14. LARSSON K. S., BOSTROEM H. TERATOGENIC ACTION OF SALICYLATES RELATED TO THE INHIBITION OF MUCOPOLYSACCHARIDE SYNTHESIS. Acta Paediatr Scand. 1965 Jan;54:43–48. doi: 10.1111/j.1651-2227.1965.tb06344.x. [DOI] [PubMed] [Google Scholar]
  15. Mato M., Uchiyama Y. Ultrastructures of glosso-palatal fusion after treatment of meclozine-hydrochloride. Virchows Arch A Pathol Anat Histol. 1975 Dec 29;369(1):7–17. doi: 10.1007/BF00432457. [DOI] [PubMed] [Google Scholar]
  16. Poswillo D. Mechanisms and pathogenesis of malformation. Br Med Bull. 1976 Jan;32(1):59–64. doi: 10.1093/oxfordjournals.bmb.a071325. [DOI] [PubMed] [Google Scholar]
  17. ROSS R. B., LINDSAY W. K. THE CERVICAL VERTEBRAE AS A FACTOR IN ETIOLOGY OF CLEFT PALATE. Cleft Palate J. 1965 Jul;36:273–281. [PubMed] [Google Scholar]
  18. Reyes P., Heidelberger C. Fluorinated pyrimidines. XXVI. Mammalian thymidylate synthetase: its mechanism of action and inhibition by fluorinated nucleotides. Mol Pharmacol. 1965 Jul;1(1):14–30. [PubMed] [Google Scholar]
  19. Santi D. V., McHenry C. S. 5-Fluoro-2'-deoxyuridylate: covalent complex with thymidylate synthetase. Proc Natl Acad Sci U S A. 1972 Jul;69(7):1855–1857. doi: 10.1073/pnas.69.7.1855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Saxén I. Associations between oral clefts and drugs taken during pregnancy. Int J Epidemiol. 1975 Mar;4(1):37–44. doi: 10.1093/ije/4.1.37. [DOI] [PubMed] [Google Scholar]
  21. Solursh M., Meier S. The selective inhibition of mucopolysaccharide synthesis by vitamin A treatment of cultured chick embryo chondrocytes. Calcif Tissue Res. 1973;13(2):131–142. doi: 10.1007/BF02015403. [DOI] [PubMed] [Google Scholar]
  22. Spivack J., Bennett J. E. Glossopalatine ankylosis. Plast Reconstr Surg. 1968 Aug;42(2):129–136. doi: 10.1097/00006534-196808000-00005. [DOI] [PubMed] [Google Scholar]
  23. Stefanovich V., Gianelly A. Preliminary studies of the lipids of normal and cleft palates of the rat. J Dent Res. 1971 Sep-Oct;50(5):1360–1360. doi: 10.1177/00220345710500055201. [DOI] [PubMed] [Google Scholar]
  24. Steffek A. J., King C. T., Derr J. E. The comparative pathogenesis of experimentally induced cleft palate. J Oral Ther Pharmacol. 1966 Jul;3(1):9–16. [PubMed] [Google Scholar]
  25. Verrusio A. C. A mechanism for closure of the secondary palate. Teratology. 1970 Feb;3(1):17–20. doi: 10.1002/tera.1420030105. [DOI] [PubMed] [Google Scholar]
  26. WOOLLAM D. H., MILLEN J. W. Effect of cortisone on the incidence of cleft-palate induced by experimental hypervitaminosis-A. Br Med J. 1957 Jul 27;2(5038):197–198. doi: 10.1136/bmj.2.5038.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wolpert L. Mechanisms of limb development and malformation. Br Med Bull. 1976 Jan;32(1):65–70. doi: 10.1093/oxfordjournals.bmb.a071326. [DOI] [PubMed] [Google Scholar]

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