Hydrocortisone-induced embryotoxicity and embryonic drug disposition in H-2 congenic mice

L. G. Roberts, Andrew G Hendrickx

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Congenic mouse strains C57BL/10Sn (B10) and B10.A/SgSn (B10A), genetically different only in the region of the H-2 complex, were compared for sensitivity to hydrocortisone-induced embryotoxicity and embryonic drug disposition. Pregnant B10A nice dosed intramuscularly with 0, 100, 150, and 200 mg hydrocortisone/kg body weight and B10 mice injected with 0, 200, 400, 600, and 800 mg/kg, both on gestational day (GD) 12, were evaluated on GD 18 for reproductive toxicity. The induction of cleft palate demonstrated a linear dose-response by probit analysis: The ED50s were 143.6 mg/kg and 512.0 mg/kg for B10A and B10 mice, respectively. Comparison of fetal weight revealed statistically significant intrauterine growth retardation at all doses administered to B10 mice. However, growth retardation was shown only in the high-dose group in the B10A strain. Embryonic drug concentrations were evaluated by administration of hydrocortisone to mice of both strains on GD 12, at the ED50 for cleft palate production in the B10A strain, with 3H-hydrocortisone (5 μci/mouse) added as a tracer. Maternal serum and embryos were analyzed for steroid content. Disposition and pharmacokinetics of 3H-hydrocortisone were similar in both strains, with the majority of serum radioactivity recovered as hydrocortisone and the major radioactive peak in embryos comigrating with cortisone. The results indicate that H-2 haplotype does not influence hydrocortisone-induced cleft palate sensitivity through an alteration of embyronic drug exposure.

Original languageEnglish (US)
Pages (from-to)341-356
Number of pages16
JournalJournal of Craniofacial Genetics and Developmental Biology
Volume7
Issue number4
StatePublished - 1987

ASJC Scopus subject areas

  • Developmental Biology

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