You are here:
COMPARISONS OF THE EFFECTS OF TCDD AND HYDROCORTISONE (HC) ON GROWTH FACTOR EXPRESSION PROVIDE INSIGHT INTO THE SYNERGISTIC INTERACTION OCCURRING IN EMBRYONIC PALATES
Citation:
Abbott, B., M. Harris, AND L. Birnbaum. COMPARISONS OF THE EFFECTS OF TCDD AND HYDROCORTISONE (HC) ON GROWTH FACTOR EXPRESSION PROVIDE INSIGHT INTO THE SYNERGISTIC INTERACTION OCCURRING IN EMBRYONIC PALATES. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-92/108 (NTIS PB92158641).
Description:
Cleft palate (CP) can be Induced In embryonic mice by a Wide range of compounds, including glucocorticoids and 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD). ydrocortisone (HC), a glucocorticoid, retards embryonic growth producing small palatal shelves, while TCDD exposure blocks the fusion of normally sized shelves. CDD induction of CP involves altered differentiation of the medial epithelIal cells. ecent studies indicate that growth factors such as EGF, TGF-a, TGF-B1 and TGF-B2 are involved in palatogenesis, regulating proliferation, differentiation, and extracellular matrix production. ynergism has been observed between HC and TCDD in which doses too low to induce CP alone are able to produce >90X incidence when coadministered. n the present study a standard teratology protocol was performed in C57BL/6N mice to examine the synergism at doses lower than those previously published. ata from this study indicate synergistic interactions at doses as low as 3 ug TCDD/kg + 1 mg NC/kg. his extreme sensitivity suggests the involvement of a receptor mediated mechanism possibly resulting In altered regulation of gene expression. echanisms of interaction were further studied by comparing growth of the shelves, fate of the medial epithelium, and expression of growth factor mRNA's and peptides. regnant mice were dosed on GDs 10-13 with HC (100 mg/kg sc) or with HC (25 mg/kg sc) + TCDD (3 ug/kg orally), doses.