Document Detail

Teratogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice lacking the expression of EGF and/or TGF-alpha.
MedLine Citation:
PMID:  11399798     Owner:  NLM     Status:  MEDLINE    
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure produces hydronephrosis and cleft palate in mice. These responses are correlated with disruption of expression of epidermal growth factor (EGF) receptor ligands, primarily EGF and transforming growth factor-alpha (TGF-alpha), and altered epithelial cell proliferation and differentiation. This research examined the role of these growth factors in TCDD-induced teratogenicity by using wild type (WT) and knockout (-/-) mice that do not express EGF, TGF-alpha, or both EGF and TGF-alpha. Pregnant females were weighed on GD 12 and dosed by gavage with either corn oil or TCDD at 24 microg/kg, 5 ml/kg. On GD 17.5, the maternal parameters evaluated included body weight, body weight gain, liver weight (absolute and adjusted for body weight). The number of implantations, live and dead fetuses, early or late resorptions, the proportion of males, fetal body weight, fetal absolute and relative liver weight, placenta weight, incidence of cleft palate, and the severity and incidence of hydronephrosis were recorded. TCDD did not affect maternal weight gain, fetal weight, or survival, but maternal and fetal liver weights and liver-to-body weight ratios were increased in all genotypes. The WT and TGF-alpha (-/-), but not the EGF (-/-) and EGF + TGF-alpha (-/-) fetuses, developed cleft palate after exposure to 24 microg TCDD/kg. Hydronephrosis was induced by TCDD in all genotypes, with the incidence in EGF + TGF-alpha (-/-) fetuses comparable to that of the WT. The incidence and severity of this defect was substantially increased in EGF (-/-) and TGF-alpha (-/-). In conclusion, this study demonstrated that expression of EGF influences the induction of cleft palate by TCDD. Also, EGF and TGF-alpha are not required for the induction of hydronephrosis, but when either is absent the response of the fetal urinary tract to TCDD is enhanced.
P L Bryant; J E Schmid; S E Fenton; A R Buckalew; B D Abbott
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  62     ISSN:  1096-6080     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2001 Jul 
Date Detail:
Created Date:  2001-06-11     Completed Date:  2001-08-16     Revised Date:  2010-09-17    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  103-14     Citation Subset:  IM    
Environmental Sciences and Engineering Department, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
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MeSH Terms
Abnormalities, Drug-Induced*
Administration, Oral
Body Weight / drug effects
Cleft Palate / chemically induced,  genetics,  pathology
Environmental Pollutants / administration & dosage,  toxicity*
Epidermal Growth Factor / deficiency*,  genetics
Hydronephrosis / chemically induced,  congenital,  genetics,  pathology
Liver / drug effects,  pathology
Mice, Inbred C57BL
Mice, Knockout
Organ Size / drug effects
Reproduction / drug effects
Teratogens / toxicity*
Tetrachlorodibenzodioxin / administration & dosage,  toxicity*
Toxicity Tests
Transforming Growth Factor alpha / deficiency*,  genetics
Grant Support
Reg. No./Substance:
0/Environmental Pollutants; 0/Teratogens; 0/Transforming Growth Factor alpha; 1746-01-6/Tetrachlorodibenzodioxin; 62229-50-9/Epidermal Growth Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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