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Embryotoxicity of Stable Isotopes and Use of Stable Isotopes in Studies of Teratogenetic Mechanisms
Author(s) -
Spielmann Horst,
Nau Heinz
Publication year - 1986
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1986.tb03561.x
Subject(s) - embryo , in vivo , isotope , teratology , incubation , metabolism , in vitro , organogenesis , chemistry , stable isotope ratio , fetus , embryogenesis , biology , kinetic isotope effect , metabolic pathway , deuterium , biochemistry , pregnancy , microbiology and biotechnology , genetics , gene , physics , quantum mechanics
Experiments on teratogenic effects of stable isotopes from our own and other laboratories are evaluated. In the first series of investigations, the enrichment of the stable isotope 13 C derived from U‐ 13 C‐glucose was studied in mouse embryos at various stages of development, including limb buds in organ culture. Preimplantation mouse embryos incubated in vitro in 13 C‐enriched medium for 48 hours showed normal development during subsequent differentiation in vitro and also in vivo after embryo transfer to foster mothers. These embryos were 15% to 20% enriched in 13 C. Administration of U‐ 13 C‐glucose to pregnant mice during organogenesis led to an increase of the absolute 13 C content of the embryo for several days after the end of isotope administration, whereas the enrichment in maternal tissue decreased. No alterations of embryonic development were detected due to stable isotope enrichment Development of cultured mouse limb buds was unaffected by incubation with 82 mol% U‐ 13 C‐glucose as judged from morphologic and biochemical criteria. The second part of the article describes the value of deuterium‐labeled drugs as probes into the mechanism of activation of teratogenic metabolites. A comparison of the pharmacokinetics as well as the teratogenicity between cyclophosphamide and some specific deuterium‐labeled analogues showed that the isotope effect observed can be related to a particular metabolic pathway crucial for teratogenic activation by this drug.