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Adriamycin effects on the chick embryo

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Abstract.

Adriamycin is an anthracycline, anti-neoplastic drug with known teratogenic effects on foetal rats in what is known as the Adriamycin rat model (ARM). This includes conditions similar to those in newborn humans, known collectively as the VACTERL association. This comprises vertebral (V), anorectal (A), cardiac (C), tracheoesophageal (TE), renal (R) and limb (L) anomalies. We designed this study to test the hypothesis that the administration of Adriamycin to chick embryos would cause similar anomalies to those in the VACTERL association seen in the ARM. Fertilized Ross eggs received Adriamycin doses from 2–50 μg into the air sac and from 0.9–6 μg into the albumin. Administration varied from day 0–3 (D0–3) with D0 being the first day of incubation. Control eggs received saline. Embryos were incubated at 38°C and a relative humidity of 70%. Embryos were recovered on D14, paraffin-embedded and transverse sections studied for morphological abnormalities. In the air sac group (n=142), 71% of Adriamycin embryos survived versus 86% of controls (n=29). In the albumin group (n=121), 42% of Adriamycin embryos survived versus 55% of controls (n=69). No embryos demonstrated anomalies consistent with the VACTERL association. Ventral defects affected 1% of surviving Adriamycin embryos versus 4% of controls in the air sac group. In the albumin group, 19.8% of surviving Adriamycin embryos had ventral defects compared to 15.7% of surviving controls. Anophthalmia affected 1% of the surviving embryos in the Adriamycin air sac group and 2% of the Adriamycin albumin group. No controls developed anophthalmia. Exencephaly affected 2% of the survivors in the Adriamycin air sac group but none of the albumin group or controls. The administration of Adriamycin to chick embryos in comparable doses and times to those used in the ARM does not appear to produce comparable effects in relation to developmental anomalies, such as the VACTERL association. Despite examining different administration routes and mimicking the ARM, by giving Adriamycin to embryos at gastrulation, we were unable to re-create the anomalies seen in the ARM.

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References

  1. Young RC, Ozols RF, Myers CE (1981) The anthracycline antineoplastic drugs. N Engl J Med 305:139–153

    CAS  PubMed  Google Scholar 

  2. Di Marco A, Arcamone F (1975) DNA complexing antibiotics: daunomycin, adriamycin and their derivatives. Arzneim Forsch 25:368–375

    Google Scholar 

  3. Thompson DJ, Molello JA, Strebing RJ et al. (1978) Teratogenicity of adriamycin and daunomycin in the rat and rabbit. Teratology 17:151–157

    CAS  PubMed  Google Scholar 

  4. Quan L, Smith DW (1973) The VATER association. Vertebral defects, anal atresia, T-E fistula with esophageal atresia, radial and renal dysplasia: a spectrum of associated defects. J Pediatr 82:104–107

    Google Scholar 

  5. Khoury MJ, Cordero JF, Greenburg F, James LM, Erickson JD (1983) A population study of the VACTERL association: evidence for its etiologic heterogeneity. Pediatrics 71: 815–820

    CAS  PubMed  Google Scholar 

  6. Kim JH, Kim PCW, Hui CC (2001) The VACTERL association: lessons from the Sonic hedgehog pathway. Clin Genet 59:306–315

    Article  CAS  PubMed  Google Scholar 

  7. Ramalho-Santos M, Melton DA, McMahon AP (2000) Hedgehog signals regulate multiple aspects of gastrointestinal development. Development 127: 2763–2772

    CAS  PubMed  Google Scholar 

  8. Rennie J (1994) Super sonic. A gene named for a video game guides development. Sci Am 270:20

    CAS  Google Scholar 

  9. Roberts DJ, Johnson RL, Burke AC et al (1995) Sonic hedgehog is an endodermal signal inducing Bmp-4 and Hox genes during induction and regionalization of the chick hindgut. Development 121:3163–3174

    CAS  PubMed  Google Scholar 

  10. Traiffort E, Charytoniuk DA, Faure H, Ruat M et al (1998) Regional distribution of Sonic Hedgehog, patched, and smoothened mRNA in the adult rat brain. J Neurochem 70:1327–1330

    CAS  PubMed  Google Scholar 

  11. Kim PCW, Mo R, Hui CC (2001) Murine models of VACTERL syndrome: role of sonic hedgehog signalling pathway. J Pediatr Surg 36:381–384

    Article  CAS  PubMed  Google Scholar 

  12. Sukegawa A, Narita T, Kameda T et al (2000) The concentric structure of the developing gut is regulated by Sonic hedgehog derived from endodermal epithelium. Development 127: 1971–1980

    CAS  PubMed  Google Scholar 

  13. Walterhouse DO, Yoon JW, Iannaccone PM (1999) Developmental pathways: Sonic hedgehog-Patched-GLI. Environ Health Perspect 107:167–171

    CAS  PubMed  Google Scholar 

  14. Motoyama J, Liu J, Mo R, Ding O, Post M, Hui CC et al (1998) Essential function of Gli2 and Gli3 in the formation of lung, trachea and oesophagus. Nat Genet 20:54–57

    Google Scholar 

  15. Mo R, Kim JH, Zhang J, Chiang C, Hui CC, Kim PCW (2001) Anorectal malformations caused by defects in sonic hedgehog signalling. Am J Pathol 159:765–774

    CAS  PubMed  Google Scholar 

  16. Gilani SH, Kreshal C (1986) Teratogenicity of cytochalasin D in chick embryos. J Environ Pathol Toxicol Oncol 6:67–72

    CAS  PubMed  Google Scholar 

  17. Vesela D, Vesely D, Jelinek R (1983) Toxic effects of ochratoxin A and citrinin, alone and in combination, on chicken embryos. Appl Environ Microbiol 45:91–93

    CAS  PubMed  Google Scholar 

  18. Cilievici O, Cordos I, Ghidus E, Moldovan A (1980) The toxic and teratogenic effect of aflatoxin B1 on the chick embryo development. Rom J Morphol Embryol 26:309–314

    CAS  Google Scholar 

  19. Gilani SH, Marano M (1980) Congenital abnormalities in nickel poisoning in chick embryos. Arch Environ Contam Toxicol 9:17–22

    CAS  PubMed  Google Scholar 

  20. Novitt AD, Gilani SH (1979) Abnormal embryogenesis induced by thiopental. J Clin Pharmacol 19:697–700

    CAS  PubMed  Google Scholar 

  21. Jelinek R, Doskocil M, Losticky C (1976) The "strait-jacket" syndrome in chicks. II. Mechanism of development. Teratology 14:327–334

    CAS  PubMed  Google Scholar 

  22. Vesely D, Vesela D, Ticha J (1987) Contamination of wheat flour with the toxigenic strain of Penicillium islandicum Sopp and the embryotoxic effect of its secondary metabolites in the chick embryo. Vet Med (Praha) 32:435–439

    Google Scholar 

  23. Poessoegel AK, Diez-Pardo JA, Morales C, Tovar JA (1999) Notochord involvement in experimental oesophageal atresia. Pediatr Surg Int 15:201–205

    Article  CAS  PubMed  Google Scholar 

  24. Gillick J, Mooney E, Giles S, Bannigan J, Puri P (2003) Notochord anomalies in the adriamycin-rat model: a morphologic and molecular basis for the VACTERL association. J Pediatr Surg 38:469–473

    Google Scholar 

  25. Orford J, Manglick P, Cass DT, Tam PPL (2001) Mechanisms for the development of oesophageal atresia. J Pediatr Surg 36:985–994

    CAS  PubMed  Google Scholar 

  26. Qi BQ, Beasley SW (1999) Relationship of the notochord to foregut development in the fetal rat model of esophageal atresia. J Pediatr Surg 34:1593–1598

    CAS  PubMed  Google Scholar 

  27. Williams AK, Qi BQ, Beasley SW (2001) Demonstration of abnormal notochord development by three-dimensional reconstructive imaging in the rat model of esophageal atresia. Pediatr Surg Int 17:21–24

    Article  CAS  PubMed  Google Scholar 

  28. Gillick J, Giles S, Bannigan S, Puri P (2002) Midgut atresias result from abnormal development of the notochord in an adriamycin rat model. J Pediatr Surg 37:719–722

    Article  CAS  PubMed  Google Scholar 

  29. Fineman RM, Schoenwolf GC (1987) Animal model: dysmorphogenesis and death in a chicken embryo model. Am J Med Genet 27:543–552

    CAS  PubMed  Google Scholar 

  30. Fineman RM, Schoenwolf GC, Huff M, Davis PL (1986) Causes of windowing-induced dysmorphogenesis (neural tube defects and early amnion deficit spectrum) in chicken embryos. Am J Med Genet 25:489–505

    CAS  PubMed  Google Scholar 

  31. Hamburger V, Hamilton HL (1951) A series of normal stages in the development of the chick embryo. J Morphol 88:49–92 (Reprinted 1992, Dev Dyn 195:231–272)

    Google Scholar 

  32. Chapman SC, Collignon J, Schoenwolf GC, Lumsden A (2001) Improved method for chick whole-embryo culture using a filter paper carrier. Dev Dyn 220:284–289

    Google Scholar 

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Authors and Affiliations

  1. The Children's Research Centre, Our Lady's Hospital for Sick Children, Crumlin, Dublin 12, Ireland

    A. Mortell & P. Puri

  2. Department of Human Anatomy, University College Dublin, Earlsfort Terrace, Dublin 2, Ireland

    J. Giles & J. Bannigan

Authors
  1. A. Mortell
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  2. J. Giles
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  3. J. Bannigan
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  4. P. Puri
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Correspondence to P. Puri.

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Mortell, A., Giles, J., Bannigan, J. et al. Adriamycin effects on the chick embryo. Ped Surgery Int 19, 359–364 (2003). https://doi.org/10.1007/s00383-003-1011-8

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  • DOI: https://doi.org/10.1007/s00383-003-1011-8

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