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Chemical teratogenesis in humans: Biochemical and molecular mechanisms

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Progress in Drug Research / Fortschritte der Arzneimittelforschung / Progrès des recherches pharmaceutiques

Abstract

In 1993, Progress in Drug Research published a review dealing with mechanisms of teratogenic/embryotoxic effects of chemicals on humans and other vertebrates [1] and covering the literature through 1992. Since 1992, significant strides have been made in understanding the biochemical and molecular mechanisms whereby chemicals are capable of eliciting birth defects as the result of prenatal exposure of conceptuses to such chemicals. These strides thus justify this review, which accordingly will focus primarily on research published since 1992 and extending through 1996. Emphasis will be directed toward those chemicals/chemical classes that are frequently regarded at present [1–5] as capable of producing birth defects in humans (“established” or “recognized” human teratogens). Most of the chemicals commonly regarded as established human teratogens (Tables 1 and 2) are xenobiotics, i.e., exogenous chemicals that are not utilized by the reference organism as nutrient materials, are not essential to the reference organism for maintenance of normal physiologic/biochemical function and homeostasis, and do not constitute a part of the conventional array of chemicals synthesized from nutrient chemicals by the reference organism in normal intermediary metabolism. Such xenobiotic chemicals are thus also often classified as “foreign”.

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References

  1. M.R. Juchau: Progr. Drug Res. 41, 9–50 (1993).

    CAS  Google Scholar 

  2. T.H. Shepard: Catalog of Teratogenic Agents, 8th ed., The Johns Hopkins University Press, Baltimore (1995).

    Google Scholar 

  3. J.L. Schardein: Chemically Induced Birth Defects, 2nd ed., Marcel Dekker, New York (1993).

    Google Scholar 

  4. J.M. Rogers and R.J. Kavlock, in: Casarett and Doull’s Toxicology: The Basic Science of Poisons, 5th ed. (CD. Klaassen, Ed.), McGraw-Hill, New York (1996), pp. 302–332.

    Google Scholar 

  5. J. Adams: Reprod. Toxicol. 7, 171–175 (1993).

    PubMed  CAS  Google Scholar 

  6. J.G. Wilson: Environment and Birth Defects, Academic Press, New York (1973).

    Google Scholar 

  7. H. Nau and W.J. Scott Jr.: Pharmacokinetics in Teratogenesis, vols. 1 and 2, CRC Press, Boca Raton, Florida (1987).

    Google Scholar 

  8. D.O. Clarke: Toxicol. Methods 3, 223–251 (1993).

    CAS  Google Scholar 

  9. I. Nulman and G. Koren: Teratology 53, 304–308 (1996).

    PubMed  CAS  Google Scholar 

  10. International Clearinghouse for Birth Defects Monitoring Systems, Abstracts of the 22nd Annual Meetings, Teratology 53, 273–281 (1996).

    Google Scholar 

  11. M. Dicker and E.A. Leighton: Am. J.Pub. Health 84, 1433–1439 (1994).

    CAS  Google Scholar 

  12. C.C. Willhite, M. Dawson and U. Reichert: Drug Metab. Rev. 28, 105–120, (1996).

    PubMed  CAS  Google Scholar 

  13. P.G. Wells and L.M. Winn: Molec. Biol. 31, 1–40 (1996).

    CAS  Google Scholar 

  14. M.R. Juchau, Q.P. Lee and A.G. Fantel: Drug Metab. Rev. 24, 195–238 (1992).

    PubMed  CAS  Google Scholar 

  15. M.R. Juchau: Drug Metab. Rev. (in press).

    Google Scholar 

  16. Paracelsus (Theophrastus ex Hohenheim Eremita): Von der Besucht, Dillingen (1567).

    Google Scholar 

  17. D.A. Karnofsky: Ann. Rev. Pharmacol. 5, 447–472 (1965).

    CAS  Google Scholar 

  18. F. Teixeira, M.T. Hojyo, R. Arenas, M.E. Vega, R. Cortes, A. Ortiz and L. Domin-guez: Lancet 344, 196–197 (1994).

    PubMed  CAS  Google Scholar 

  19. T.D. Stephens: Teratology 41, 239–246 (1988).

    Google Scholar 

  20. R.J. D’Amato, M.S. Loughnan, E. Flynn and J.Folkman: Proc. Soc. Natl. Acad. Sci. USA 91, 4082–4085 (1994).

    Google Scholar 

  21. R. Neubert, N. Hinz, R. Thiel and D. Neubert: Life Sci. 58, 295–316 (1996).

    PubMed  CAS  Google Scholar 

  22. A.C. Nogueira, R. Neubert, A. Felies, U. Jacob-Mueller, E. Frankus and D. Neubert: Life Sci. 58, 337–348 (1996).

    PubMed  CAS  Google Scholar 

  23. R.R. Arlen and P.G. Wells: J.Pharmacol. Exper.Therap. 277, 1649–1658 (1996).

    CAS  Google Scholar 

  24. R.R. Arlen and P.G. Wells: Fed. Am. Soc. Exp. Biol. J. 4, A608 (1990).

    Google Scholar 

  25. L. Liu and P.G. Wells: Free Rad. Biol. Med. 19, 639–648 (1995).

    PubMed  CAS  Google Scholar 

  26. T. Parman, C. Guoman, T.M. Bray and P.G. Wells: App.Toxicol.30 (Suppl. 1, P.2: The Toxicologist) 246 (No. 1260) (1996).

    Google Scholar 

  27. B. Vaisman: Teratology 53, 283–284 (1996).

    PubMed  CAS  Google Scholar 

  28. J. Ashby and H. Tinwell: Nature 375, 453 (1995).

    PubMed  CAS  Google Scholar 

  29. M. Lishner, D. Zemlickis, P. Degendorfer, T. Panzarella, S.B. Sutcliffe and G. Koren: Br. J.Cancer 65, 114–117 (1992).

    PubMed  CAS  Google Scholar 

  30. A.J. Zanov, J. Anderson, D.F. Cella, E. Zuckerman, A.B. Korablith, J.C. Holland, A.F. Kantof and F.P Li: Cancer 70, 688–692 (1992).

    Google Scholar 

  31. J.M. Piper, E.F. Mitchell and WA. Ray: Obstet. Gynecol. 82, 348–352 (1993).

    PubMed  CAS  Google Scholar 

  32. P. Burtin, A. Taddio, O. Ariburnu, T.R. Einarson and G. Koren: Am. J.Obstet. Gynecol. 172, 525–529 (1995).

    PubMed  CAS  Google Scholar 

  33. J. Waalen: J.Nat. Cancer Inst. 83, 900–902 (1991).

    PubMed  CAS  Google Scholar 

  34. H.O. Nicholson: J. Obst. Gynecol. Br. Com. 75, 307–312 (1968).

    CAS  Google Scholar 

  35. J.N. Yamazaki and W.J. Schull: J. Amer. Med. Assn. 264, 605–610 (1990).

    CAS  Google Scholar 

  36. D. Zemlickis, M. Lishner, R. Erlich and G. Koren. Teratogen. Carcinogen. Mutagen 13, 139–143 (1993).

    CAS  Google Scholar 

  37. M. Schmidt and EM. Salzano: Acta Genet. Med. Gemellol. (Roma) 29, 295–297 (1980).

    CAS  Google Scholar 

  38. C. Harris, K.L. Stark and M.R. Juchau: Teratology 37, 577–590 (1988).

    PubMed  CAS  Google Scholar 

  39. R. Hiranruengchok and C. Harris: Teratology 52, 205–214 (1995).

    PubMed  CAS  Google Scholar 

  40. E. Chu, J.L. Grem, P.G. Johnston and C.J. Allegro: Stem Cells 14, 41–46 (1996).

    PubMed  CAS  Google Scholar 

  41. J.M. DeSesso and G.C. Goeringer: Teratology 45, 271–283 (1992).

    PubMed  CAS  Google Scholar 

  42. J.M. DeSesso and G.C. Goeringer: Teratology 43, 201–215 (1991).

    PubMed  CAS  Google Scholar 

  43. M.R. Juchau, Q.P. Lee and A.G Fantel: Drug Metab. Rev. 24, 195–238 (1992).

    PubMed  CAS  Google Scholar 

  44. B.A. Chabner, in: Cancer Chemotherapy: Principles and Practice, 2nd ed. (B.A. Chab-ner and D.L. Longo, Eds.), IP. Lippincott Co., Philadelphia (1996), pp. 234–268.

    Google Scholar 

  45. T. Mikita and GP. Beardsley: Biochemistry 27, 4698–4705 (1988).

    PubMed  CAS  Google Scholar 

  46. R.M. Zucker, K.H. Elstein, D.L. Shuey and J.M. Rogers: Teratology 51, 37–45 (1995).

    PubMed  CAS  Google Scholar 

  47. D.L. Shuey, A.R. Buckalew, T.S. Wilke, J.M. Rogers and B.D. Abbott: Teratology 50, 379–386 (1994).

    PubMed  CAS  Google Scholar 

  48. W. Bollag: FASEB J. 10, 938–940 (1996).

    PubMed  CAS  Google Scholar 

  49. D.R. Soprano and K.J. Soprano: Ann. Rev. Nutr. 15, 111–132 (1995).

    CAS  Google Scholar 

  50. A.L. Means and L.J. Gudas: Ann. Rev. Biochem. 64, 201–233 (1995).

    PubMed  CAS  Google Scholar 

  51. G.M. Morriss-Kay and N. Sokolova: FASEB J. 10, 961–968 (1996).

    PubMed  CAS  Google Scholar 

  52. J.M. Creech Kraft and M.R. Juchau: Drug Metab. Dispos. 23, 1058–1072 (1995).

    Google Scholar 

  53. K. Eckhardt and G. Schmitt: Tox. Letts. 70, 299–308 (1994).

    CAS  Google Scholar 

  54. G.V. Raymond, B.A. Buehler, R.H. Finnell and L.B. Holmes: Teratology 51, 55–56 (1995).

    PubMed  CAS  Google Scholar 

  55. P.G. Wells and L.M. Winn: Crit. Rev. Biochem. Mol. Biol. 31, 1–40 (1996).

    PubMed  CAS  Google Scholar 

  56. B.R. Danielsson, K. Danielsson and T. Tomson: Teratology 52, 252–259 (1995).

    PubMed  CAS  Google Scholar 

  57. M. Sato, M. Shirota and T. Nagao: Teratology 52, 143–148 (1995).

    PubMed  CAS  Google Scholar 

  58. G.L. Barnes Jr., B.D. Mariani, R.S. Tuan: Teratology 54, 93–102 (1996).

    PubMed  CAS  Google Scholar 

  59. D.K. Hansen, TE Grafton, S.L. Dial, T.A. Gehring and P.H. Siitonen: Teratology 52, 211–285 (1995).

    Google Scholar 

  60. R.H. Finnell, G.D. Bennett, IT. Slattery, B.M. Amore, M. Bajpai and R.H. Levy: Teratology 52, 324–332 (1995).

    PubMed  CAS  Google Scholar 

  61. D.K. Hansen, S.L. Dial, K.K. Terry and T.F. Grafton: Teratology 54, 45–51 (1996).

    PubMed  CAS  Google Scholar 

  62. W.A. Chen, K.H. Andersen and J.R. West: Teratology 50, 250–255 (1994).

    PubMed  CAS  Google Scholar 

  63. L.E. Kotch and K.K. Sulik: Am. I Med. Genet. 44, 168–176 (1992).

    CAS  Google Scholar 

  64. L.E. Kotch, S-Y. Chen and K.K. Sulik: Teratology 52, 128–136 (1995).

    PubMed  CAS  Google Scholar 

  65. M.R. Juchau and H.L. Yang: Fund. Appl. Toxicol. 34, 166–168 (1996).

    Google Scholar 

  66. S.P. Carpenter, J.M. Lasker and J.L. Raucy: Molec. Pharmacol. 49, 260–268 (1996).

    CAS  Google Scholar 

  67. L. Deltour, H.L. Ang and G. Duester: FASEB J. 10, 1050–1057 (1996).

    PubMed  CAS  Google Scholar 

  68. H. Chen, H.L. Yang, M.J. Namkung and M.R. Juchau: Teratology 54, 12–19 (1996).

    PubMed  CAS  Google Scholar 

  69. H. Chen, MJ. Namkung and M.R. Juchau: Alcoholism: Clin. Exp. Res. 20, 942–948 (1996).

    CAS  Google Scholar 

  70. T.A. Slotkin, F.I Seidler, R.I Kavlock and J.V. Bartolome: Teratology 45, 303–312 (1992).

    PubMed  CAS  Google Scholar 

  71. J.M. Creech Kraft, C.C. Willhite and M.R. Juchau: J. Craniofac. Gen. Dev. Biol. 14, 75–86 (1994).

    Google Scholar 

  72. H.F. Chambers and M.A. Sande, in: The Pharmacologic Basis of Therapeutics, 9th ed. (J.G. Hardman and L.E. Limbird, Eds.) McGraw-Hill, New York (1996), pp. 1103–1121.

    Google Scholar 

  73. H.C Neu and C.L. Bendush: J. Infect. Dis. 134, S206–S218 (1976).

    PubMed  Google Scholar 

  74. S.Q. Cohlan, G. Bevelander and T. Tiamsic: Am. J. Dis. Child. 105, 453–461 (1963).

    Google Scholar 

  75. R.A. Goyer, in: Casarett and Doull’s Toxicology: The Basic Science of Poisons, 5th ed. (C.D. Klaassen, Ed.), McGraw-Hill, New York (1996), pp. 691–736.

    Google Scholar 

  76. T.M. Burbacher: Appl. Toxicol. 25, 168–171 (1995).

    Google Scholar 

  77. D. Bellinger: Teratology 50, 367–374 (1994).

    PubMed  CAS  Google Scholar 

  78. E.K. Silbergeld and L. Watson: Fund. Appl. Toxicol. 25, 167–168 (1995).

    Google Scholar 

  79. E.K. Silbergeld: FASEB J. 6, 3201–3206 (1992).

    PubMed  CAS  Google Scholar 

  80. R.E. Peterson, H.M. Thoebald and G.L. Kimmel: Grit Rev.Toxicol. 23, 293–335 (1993).

    Google Scholar 

  81. O. Hankinson: Toxicol. 35, 307–340 (1995).

    CAS  Google Scholar 

  82. Y.L. Guo, G.H. Lambert and C. Hsu: Env. Health Persp. 103, 117–122 (1995).

    CAS  Google Scholar 

  83. B.D. Abbott, G.H. Perdew and L.S. Birnbaum: Toxicol. Appl. Pharmacol 126, 16–25 (1994).

    PubMed  CAS  Google Scholar 

  84. L. Wilkins, H.W. Jones, G.H. Holman and R.S. Stempfei: J. Clin. Endocrinol. Metab. 18, 559–585 (1958).

    PubMed  CAS  Google Scholar 

  85. C. Chang, J. Kokontis and S.T. Liao: Science 240, 324–326 (1988).

    PubMed  CAS  Google Scholar 

  86. R. Mittendorf: Teratology 51, 435–446 (1995).

    PubMed  CAS  Google Scholar 

  87. B.K. Beyer, K.L. Stark, A.G. Fantel and M.R. Juchau: Toxicol. Appl. Pharmacol. 98, 113–128 (1989).

    PubMed  CAS  Google Scholar 

  88. W.L. Shaul, H. Emery and J.G. Hall: Am. J. Dis. Child. 129, 360–362 (1975).

    PubMed  CAS  Google Scholar 

  89. J.G. Hall, R.M. Pauli and K.M. Wilson: Am. J. Med. 68, 122–140 (1980).

    PubMed  CAS  Google Scholar 

  90. A.M. Howe and WS. Webster: Teratology 46, 379–390 (1992).

    PubMed  CAS  Google Scholar 

  91. P.W. Majerus, G.J. Broze Jr., J.P. Miletich and D.M. Tollefsen, in: The Pharmacologic Basis of Therapeutics, 9th ed. (J.G. Hardman and L.E. Limbird, Eds.), McGraw-Hill, New York (1996), pp. 1341–1359.

    Google Scholar 

  92. B. Sommer, M. Bickel, W Hofstetter and A. Wetterwald: Bone 19, 371–380 (1996).

    PubMed  CAS  Google Scholar 

  93. J.R. Cairns and P.A. Price: J. Bone Miner. Res. 9, 1989–1997 (1994).

    PubMed  CAS  Google Scholar 

  94. M. Barr Jr.: Teratology 50, 399–409 (1994).

    PubMed  CAS  Google Scholar 

  95. G.H. Williams: New Engl. J. Med. 319, 1517–1525 (1988).

    PubMed  CAS  Google Scholar 

  96. S.G. Spence, A.G. Zacchei, L.L. Lee, C.L. Baldwin, R.A. Berna, B.A. Mattson and R.S. Eydelloth: Teratology 53, 245–252 (1996).

    PubMed  CAS  Google Scholar 

  97. J.R. DiFranza and R.A. Lew: J. Farn. Pract. 40, 385–394 (1995).

    CAS  Google Scholar 

  98. C.R. Wasserman, G.M. Shaw, C.D. O’Malley, M.M. Tolarova and EJ. Lammer: Teratology 53, 261–267 (1996).

    PubMed  CAS  Google Scholar 

  99. C.M. Toison, F.J. Seidler, E.C McCook and T.A. Slotkin: Teratology 52, 298–305 (1995).

    Google Scholar 

  100. M.K. Sanyal, Y Li and K. Belanger: Reprod. Toxicol. 8, 411–418 (1994).

    PubMed  CAS  Google Scholar 

  101. B.B. Little, G.N Wilson and G. Jackson: Teratology 54, 145–150 (1996).

    PubMed  CAS  Google Scholar 

  102. L. Slutsker: Obstet. Gynecol. 79, 778–789 (1992).

    PubMed  CAS  Google Scholar 

  103. A.G. Fantel, C.V. Barber and B. Mackler: Teratology 46, 285–292 (1992).

    PubMed  CAS  Google Scholar 

  104. J.B. Fisher, R.B. Poturri, M. Collins, E. Resnick and E.F. Zimmerman: Teratology 49, 182–191 (1994).

    PubMed  CAS  Google Scholar 

  105. E.F. Zimmerman, R.B. Poturri, E. Resnick and J.E. Fisher: Teratology 49, 192–201 (1994).

    PubMed  CAS  Google Scholar 

  106. A.G. Fantel: Teratology 53, 196–217 (1996).

    PubMed  CAS  Google Scholar 

  107. M.R. Brzezinski, T.L. Abraham, C.L. Stone, R.A. Dean and W.F. Bosron: Biochem. Pharmacol. 48, 1747–1755 (1994).

    PubMed  CAS  Google Scholar 

  108. W.A. Chen, R.E. McAlhany Jr., S.E. Maier and J.R. West: Teratology 53, 145–151 (1996).

    PubMed  CAS  Google Scholar 

  109. F.W. Rosa: Teratology 33, 127–131 (1986).

    PubMed  CAS  Google Scholar 

  110. H. Takami: Int. Surg. 79, 89–90 (1994).

    PubMed  CAS  Google Scholar 

  111. G.L. Arnold, R.S. Kirby, S. Langendoerger and L. Wilkins-Haug: Pediatrics 93, 216–220 (1994).

    PubMed  CAS  Google Scholar 

  112. J.M. Donald, K. Hooper and C. Hopenhayn-Rich: Perspectives 94, 237–244 (1991).

    CAS  Google Scholar 

  113. H.J. Klimisch, J. Hellwig and A. Hoffman: Arch. Toxicol. 66, 373–381 (1992).

    PubMed  CAS  Google Scholar 

  114. R. Wood, in: Neurobehavioral Toxicity: Analyses and Interpretation (B. Weiss and J. O’Donoghue, Eds.), Raven Press, New York (1994), pp. 367–375.

    Google Scholar 

  115. U. Nicolini and G. Monni: Lancet 336, 1258–1259 (1990).

    PubMed  CAS  Google Scholar 

  116. P.A.L. Lancaster, E.L. Pedisich, C.C. Fisher and R.D. Robertson: I J. Perinat. Med. 20 (Suppl.l), 262 (1992).

    Google Scholar 

  117. J.G. van der Pol, H. Wolf, K. Boer, P.E. Treffers, N.J. Leschot, H.A. Hey and A. Vos: Br. J. Obstet. Gynaecol. 99, 141–143 (1992).

    PubMed  Google Scholar 

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  1. Department of Pharmacology, School of Medicine, University of Washington, Box 357280, Seattle, WA, 98195, USA

    Mont R. Juchau

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    Ernst Jucker

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Juchau, M.R. (1997). Chemical teratogenesis in humans: Biochemical and molecular mechanisms. In: Jucker, E. (eds) Progress in Drug Research / Fortschritte der Arzneimittelforschung / Progrès des recherches pharmaceutiques. Progress in Drug Research / Fortschritte der Arzneimittelforschung / Progrès des recherches pharmaceutiques, vol 49. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8863-9_2

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