Effect of 20-Methylcholanthrene on Mouse Embryos. Ii. Strain C3h (Jax)

Savkur, Lalita D.; Batra, B. K.; Sridharan, B. N.

doi:10.1530/jrf.0.0020374

Cited by 10 publications

References 10 publications

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Morphogenesis of cleft palate induced by exogenous factors. III. Intraamniotic application of hydrocortisone in mice

Dostál¹

1971

Teratology

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In analyzing the morphogenesis of an experimentally induced congenital defect, estimation of the direct effect of the teratogen on offspring is of a great importance. In order to avoid the probable modification of the teratogenic action of a given substance caused by the placental barrier and maternal metabolism, it is useful to apply the teratogen directly into the amniotic sac of the embryo or fetus. However, it has been claimed that puncture of the amniotic sac both in mice and rats may itself induce cleft palate. An intraamnioticinjection method worked out in our laboratory diminishes the occurrence of cleft palate caused by nonspeciflc factors to a uniform and fairly negligible level. The application is performed by means of a glass micropipette provided with sharp, beveled tip. Using this method hydrocortisone was injected into the amniotic sacs of embryos and fetuses of randombred H-Velaz mice, and it was shown that administration on day 12, 13, or 14 of gestation induced cleft palate. The direct action of corticoids upon the morphogenetic system of the palatine shelves is therefore supposed.

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Morphogenesis of cleft palate induced by exogenous factors. III. Intraamniotic application of hydrocortisone in mice

Dostál¹

1971

Teratology

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Genetically mediated induction of drug‐metabolizing enzymes associated with congenital defects in the mouse

Lambert

Nebert

1977

Teratology

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Various polycyclic aromatic compounds induce certain monooxygenase activities, including aryl hydrocarbon (benzo[a]pyrene) hydroxylase (EC 1.14.14.2), and cytochrome P1-450 in the liver and many nonhepatic tissues of the mouse. This induction process is controlled by the Ah locus. Genetic differences that have been shown in the past to be associated with the Ah locus include an increased susceptibility to chemical carcinogenesis, mutagenicity in vitro, and drug toxicity--manifested as hepatic necrosis, aplastic anemia, or shortened survival time. Pregnant mice received a single injection of 3-methylcholanthrene or 7,12-dimethylbenz[a] anthracene between day 5 and day 13 of gestation, and the uterine contents were examined on day 18. Striking increases were observed in the incidence of MC-1 and DMBA-induced resorptions and congenital malformations in the aromatic hydrocarbon "responsive" C57BL/6N inbred strain, and of DMBA-induced resorptions in the "responsive" C3H/HeN and BALB/cAnN strains--when compared with the similarly treated genetically "nonresponsive" AKR/N strain. These data suggest but do not prove that an association exists between the Ah locus and developmental toxicity, i.e., teratogenesis. Although numerous teratogenic differences among inbred mouse strains have previously reported, this study is unique in that the genetic differences in teratogenicity observed were predicted in advance on the basis of known differences among these strains in polycyclic hydrocarbon metabolism regulated by the Ah locus.

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The Murine Ah locus: In utero toxicity and teratogenesis associated with genetic differences in benzo[a]pyrene metabolism

1979

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Benzo[a]pyrene, at dose between 50 and 300 mg per kg body weight given at Day 7 or 10 of gestation, causes in utero toxicity and teratogenicity more so in genetically "responsive" C57BL/6 than in "nonresponsive" AKR inbred mice. With the use of AKR X (C57BL/6) (AKR)F1 and (C57BL/6) (AKR)F1 X AKR backcrosses, it was shown that allelic differences at the Ah locus in the fetus can be correlated with dysmorphogenesis. If the mother is nonresponsive (Ahd/Ahd), the Ahb/Ahd genotype in the fetus is associated with more stillborns and resorptions, decreased fetal weight, increased congenital anomalies, and enhanced P1-450-mediated covalent binding of BP metabolites to fetal protein and DNA, when compared with the Ahd/Ahd genotype in the fetus from the same uterus. If the mother is responsive (Ahb/Ahd), however, none of these parameters can be distinguished between Ahb/Ahd and Ahd/Ahd individuals in the same uterus, presumably because enhanced BP metabolism in maternal tissues and placenta cancels out these differences between individual fetuses. Of particular interest in our study is the fact that the mother and the father both must be of a particular genotype before differences in teratogenesis among fetuses (due to their genotype) will be expressed. These data might provide an example in attempting to explain clinically why only one child is affected with an apparent "drug-induced syndrome" although the mother has taken the same dose of the particular drug during each of numerous pregnancies.

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Effect of 20-Methylcholanthrene on Mouse Embryos. Ii. Strain C3h (Jax)

Cited by 10 publications

References 10 publications

Morphogenesis of cleft palate induced by exogenous factors. III. Intraamniotic application of hydrocortisone in mice

Morphogenesis of cleft palate induced by exogenous factors. III. Intraamniotic application of hydrocortisone in mice

Genetically mediated induction of drug‐metabolizing enzymes associated with congenital defects in the mouse

The Murine Ah locus: In utero toxicity and teratogenesis associated with genetic differences in benzo[a]pyrene metabolism

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