Human Genetics

, Volume 51, Issue 2, pp 183–194 | Cite as

Transplacental mutagenesis: The micronucleus test on fetal mouse blood

  • M. -T. King
  • D. Wild
Original Investigations


The induction of cytogenetic damage (micronuclei) in mouse fetal blood was studied with four selected mutagens: cyclophosphamide, procarbazine, trenimon, and mitomycin-C. For comparison the standard micronucleus test on maternal bone marrow was also performed. In contrast to the results obtained from maternal bone marrow the changes in the cellular composition in fetal blood were only slight after treatment with mutagens. A significant and dosepdependent increase in the incidence of micronucleated fetal blood cells was found with all four mutagens. The inducibility of micronuclei by indirect mutagens was particularly interesting. The three mutagens other than mitomycin-C induced a higher frequency of micronucleated polychromatic erythrocytes in fetal blood cells than in maternal bone marrow. The results indicate that this modified micronucleus test is well suited and useful for mutagenicity screening of environmental chemicals and especially for assessment of risks to the fetus when pregnant females are exposed to environmental chemicals.


Internal Medicine Cyclophosphamide Metabolic Disease Environmental Chemical Mutagenicity Screening 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Brock, N., Gross, R., Hohorst, H.-J., Klein, H. O., Schneider, B.: Activation of cyclophosphamide in man and animals. Cancer 27, 1512–1529 (1971)PubMedGoogle Scholar
  2. Fahrig, R.: The mammalian spot test: a sensitive in vivo method for the detection of genetic alterations in somatic cells of mice. In: Chemical mutagens, principles and methods for their detection, Vol. 5 (A. Hollaender, F. J. de Serres, eds.), pp. 151–176. New York-London: Plenum Press 1978Google Scholar
  3. Fantoni, A., de la Chapelle, A., Marks, P. A.: Synthesis of embryonic hemoglobins during erythroid cell development in fetal mice. J. Biol. Chem. 244, 675–681 (1969)PubMedGoogle Scholar
  4. Inui, N., Nishi, Y., Taketomi, M.: Mutagenic effect of orally given AF-2 on embryonic cells in pregnant syrian hamsters. Mutat. Res. 57, 69–75 (1978)PubMedGoogle Scholar
  5. Iyer, V. N., Szybalski, W.: Mitomycins and porfiromycin: chemical mechanism of activation and cross-linking of DNA. Science 145, 55–58 (1964)PubMedGoogle Scholar
  6. Klose, J.: Protein mapping as a tool for investigating mutagenic and teratogenic effects in mouse embryos. In: New approaches to the evaluation of abnormal embryonic development (D. Neubert, H.-J. Merker, eds.), pp. 375–387. Stuttgart: Thieme 1975Google Scholar
  7. Larsen, C. D.: Pulmonary-tumor induction by transplacental exposure to urethan. J. Nat. Cancer Inst. 8, 63–70 (1947)Google Scholar
  8. Lee, I. P., Dixon, R. L.: Mutagenicity, carcinogenicity and teratogenicity of procarbazine. Mutat. Res. 55, 1–14 (1978)PubMedGoogle Scholar
  9. Maier, P., Schmid, W.: Ten model mutagens evaluated by the micronucleus test. Mutat. Res 40, 325–338 (1976)PubMedGoogle Scholar
  10. Matter, B. E., Schmid, W.: Trenimon-induced chromosomal damage in bone-marrow cells of six mammalian species, evaluated by the micronucleus test. Mutat. Res. 12, 417–425 (1971)PubMedGoogle Scholar
  11. Matter, B. E., Grauwiler, J.: Micronuclei in mouse bone-marrow cells. A simple in vivo model for the evaluation of drug-induced chromosomal aberrations. Mutat. Res. 23, 239–249 (1974)PubMedGoogle Scholar
  12. Nau, H., Liddiard, C., Bass, R., Lange, J., Haase, V.: Der diaplazentare Übergang sowie der fetale Metabolismus von Pharmaka in der ersten Hälfte der menschlichen Schwangerschaft. In: Embryotoxikologische Probleme in der Arzneimittelforschung (B. Schnieders, G. Stille, P. Grosdanoff, eds.), pp. 89–96. Berlin: Dietrich Reimer 1978Google Scholar
  13. Pearse, A. G. E.: Histochemistry, theoretical and applied. London: J. & A. Churchill Ltd. 1968Google Scholar
  14. Russell, E. S., Bernstein, S. E.: Blood and blood formation. In: Biology of the laboratory mouse (E. L. Green, ed.), pp. 351–372. New York: Dover 1966Google Scholar
  15. Schmid, W.: Chemical mutagen testing on in vivo somatic mammalian cells. Agents and actions 3, 77–85 (1973)PubMedGoogle Scholar
  16. Schmid, W.: The micronucleus test. Mutat. Res. 31, 9–15 (1975)PubMedGoogle Scholar
  17. Sehgal, C. B., Hutton, J. J.: Homogenates of pregnant rat and fetal tissues metabolize carcinogens to mutagens detected by Salmonella typhimurium TA 98 and TA 100. Mutat. Res. 46, 325–344 (1977)Google Scholar
  18. Southard, J. L., Wolfe, H. G., Russell, E. S.: Artificial insemination of dystrophic mice with mixtures of spermatozoa. Nature 208, 1126–1127 (1965)Google Scholar
  19. Tarbutt, R. G., Cole, R. J.: Cell population kinetics of erythroid tissue in the liver of foetal mice. J. Embryol. exp. Morph. 24, 429–446 (1970)PubMedGoogle Scholar
  20. Von Ledebur, M., Schmid, W.: The micronucleus test, methodological aspects. Mutat. Res. 19, 109–117 (1973)PubMedGoogle Scholar
  21. Weitzel, G., Schneider, F., Kummer, D., Ochs, H.: Cytostatischer Wirkungsmechanismus von Natulan. Z. Krebsforsch. 70, 354–365 (1968)PubMedGoogle Scholar
  22. Wheldon, T. E., Kirk, J., Orr, J. S., Paul, J., Conkie, D.: Kinetics of development of embryonic erythroid cells. Cell tissue kinet. 7, 181–188 (1974)PubMedGoogle Scholar
  23. Wild, D.: Cytogenetic effects in the mouse of 17 chemical mutagens and carcinogens evaluated by the micronucleus test. Mutat. Res. 56, 319–327 (1978)PubMedGoogle Scholar
  24. Yaffe, S. J., Rane, A., Sjöqvist, F., Boreus, L. O., Orrenius, S.: The presence of a monooxygenase system in human fetal liver microsomes. Life Sci. 9, part II, 1189–1200 (1970)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • M. -T. King
    • 1
  • D. Wild
    • 1
  1. 1.Zentrallaboratorium für MutagenitätsprüfungFreiburgFederal Republic of Germany

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