Comparisons of the effects of TCDD and hydrocortisone on growth factor expression provide insight into their interaction in the embryonic mouse palate

Technical Report · Wed Jan 01 00:00:00 EST 1992

OSTI ID:5512560

Abbott, B D; Harris, M W; Birnbaum, L S

Cleft palate (CP) can be induced in embryonic mice by a wide range of compounds, including glucocorticoids and 2,3,7,8-tyetrachlorodibenzo-p-dioxin (TCDD). Hydrocortisone (HC), a glucocorticoid, retards embryonic growth producing small palatal shelves, while TCDD exposure blocks the fusion of normally sized shelves. TCDD induction of CP involves altered differentiation of the medial epithelial cells. Recent studies indicate that growth factors such as EGF, TGF-alpha, TGF-beta1, and TGF-beta2 are involved in palatogenesis, regulating proliferation, differentiation, and extracellular matrix production. A synergism has been observed between HC and TCDD in which doses too low to induce CP alone are able to produce >90% incidence when coadministered. In the present study a standard teratology protocol was performed in C57BL/6N mice to examine the synergism at doses lower than those previously published. Data from the study indicate synergistic interactions at doses as low as 3 micrograms TCDD/kg + 1 mg HC/kg. This extreme sensitivity suggests the involvement of a receptor-mediated mechanism possibly resulting in altered regulation of gene expression. (Copyright (c) 1992 Wiley-Liss, Inc.)

• Research Organization: Environmental Protection Agency, Research Triangle Park, NC (United States). Health Effects Research Lab.
• OSTI ID: 5512560
• Report Number(s): PB-92-158641/XAB; EPA-600/J-92/108
• Resource Relation: Other Information: Pub. in Teratology 45, n1 p35-53 Jan 92. Prepared in cooperation with National Inst. of Environmental Health Sciences, Research Triangle Park, NC
• Country of Publication: United States
• Language: English

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
DIOXIN
TERATOGENESIS
HYDROCORTISONE
BIOLOGICAL EFFECTS
ORAL CAVITY
MORPHOLOGICAL CHANGES
CELL DIFFERENTIATION
ELECTRON MICROSCOPY
EMBRYOS
EPITHELIUM
GENE REGULATION
GROWTH FACTORS
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ANIMAL TISSUES
ANIMALS
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HETEROCYCLIC COMPOUNDS
HORMONES
HYDROXY COMPOUNDS
KETONES
MAMMALS
MICROSCOPY
MITOGENS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PREGNANES
PROTEINS
RODENTS
STEROID HORMONES
STEROIDS
TISSUES
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560300* - Chemicals Metabolism & Toxicology