Hydrocortisone-induced embryotoxicity and embryonic drug disposition in H-2 congenic mice
Congenic mouse strains C57BL/10Sn (B10) and B10.A/SgSn(B10A), genetically different only at the H-2 complex, were compared for sensitivity to glucocorticoid-induced embryotoxicity and embryonic drug disposition. B10A mice dosed intramuscularly with 0, 100, 150 and 200 mg hydrocortisone/kg body weight on gestational day twelve, and B10 mice injected with 0, 200, 400, 600, and 800 mg/kg, were evaluated at dissection on gestational day eighteen for signs of toxicity. In both strains, probit analysis of cleft palate production demonstrated a linear dose response. The ED50 for cleft palate production demonstrates a linear dose response. The ED50 for cleft palate production in B10A mice was 143.6 mg/kg and 512.0 mg/kg for the B10 strain. Embryonic exposure was evaluated by administration of /sup 3/H-hydrocortisone (5 uCi/mouse) to pregnant mice on day twelve of gestation, at the ED50 for cleft palate production in B10A strain. The purposes of the experiment were to quantify the difference in susceptibility to steroid-induced cleft palate, determine if a milder manifestation of embryotoxicity, fetal growth retardation, occurred at sub-clefting dosages, and determine if the difference in sensitivity to hydrocortisone-induced embryotoxicity was the result of an underlying difference in embryonic exposure to the teratogen.
- Research Organization:
- California Univ., Davis (USA)
- OSTI ID:
- 6583866
- Resource Relation:
- Other Information: Thesis (Ph. D)
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
EMBRYOS
SENSITIVITY
HYDROCORTISONE
TERATOGENESIS
TOXICITY
DOSE-RESPONSE RELATIONSHIPS
GENETIC VARIABILITY
MICE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ADRENAL HORMONES
ANIMALS
BIOLOGICAL VARIABILITY
CORTICOSTEROIDS
GLUCOCORTICOIDS
HORMONES
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KETONES
LABELLED COMPOUNDS
MAMMALS
ORGANIC COMPOUNDS
PREGNANES
RODENTS
STEROID HORMONES
STEROIDS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550501 - Metabolism- Tracer Techniques