PMID- 15880701
OWN - NLM
STAT- MEDLINE
DCOM- 20051004
LR  - 20161124
IS  - 1542-0752 (Print)
IS  - 1542-0752 (Linking)
VI  - 73
IP  - 6
DP  - 2005 Jun
TI  - Effects of epidermal growth factor (EGF), transforming growth factor-alpha 
      (TGFalpha), and 2,3,7,8-tetrachlorodibenzo-p-dioxin on fusion of embryonic 
      palates in serum-free organ culture using wild-type, EGF knockout, and TGFalpha 
      knockout mouse strains.
PG  - 447-54
AB  - BACKGROUND: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is teratogenic in mice, 
      producing cleft palate (CP). TCDD exposure disrupts expression of epidermal 
      growth factor (EGF) receptor, EGF, and transforming growth factor-alpha 
      (TGFalpha) in the palate and affects proliferation and differentiation of medial 
      epithelial cells. EGF knockout embryos are less susceptible to the induction of 
      CP by TCDD. This study used palate organ culture to examine the hypothesis that 
      EGF enables a response to TCDD. METHODS: The midfacial tissues from wild-type 
      (WT), EGF knockout, C57BL/6J, and TGFalpha knockout embryos were placed in organ 
      culture on gestational day (GD) 12. Palatal explants were cultured for 4 days in 
      serum-free Bigger's (BGJ) medium with 0.1% dimethyl sulfoxide (DMSO) or 1 x 
      10(-8) M TCDD with or without 2 ng of EGF/ml, 1 or 2 ng of TGFalpha/ml. Effects 
      on palatal fusion were evaluated on day 4 of culture. EGF levels in explants and 
      medium were determined using Luminex technology. RESULTS: In serum-free, control 
      medium, palates from all of the strains fused. EGF knockout palates cultured with 
      TCDD (no EGF) fused, but those cultured with TCDD + 2 ng of EGF/ml failed to fuse 
      (p < 0.05 vs. control or TCDD without EGF). TGFalpha knockout palates failed to 
      fuse when cultured with TCDD + 2 ng of TGFalpha/ml. EGF levels increased in 
      tissue and accumulated in the medium after 24 hr of culture. CONCLUSIONS: This 
      study demonstrated that providing EGF to the palates of EGF knockout mice 
      restored the response to TCDD. These studies support the hypothesis that the 
      mechanism for induction of CP by TCDD is mediated via the EGFR pathway.
CI  - (c) 2005 Wiley-Liss, Inc.
FAU - Abbott, Barbara D
AU  - Abbott BD
AD  - Reproductive Toxicology Division, National Health and Environmental Effects 
      Research Laboratory, Office of Research and Development, U.S. Environmental 
      Protection Agency, Research Triangle Park, NC 27711, USA. Abbott.barbara@epa.gov
FAU - Buckalew, Angela R
AU  - Buckalew AR
FAU - Leffler, Korin E
AU  - Leffler KE
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Birth Defects Res A Clin Mol Teratol
JT  - Birth defects research. Part A, Clinical and molecular teratology
JID - 101155107
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Transforming Growth Factor alpha)
RN  - 62229-50-9 (Epidermal Growth Factor)
SB  - IM
MH  - Animals
MH  - Culture Media, Serum-Free
MH  - Epidermal Growth Factor/genetics/*pharmacology/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Organ Culture Techniques
MH  - Polychlorinated Dibenzodioxins/*pharmacology
MH  - Transforming Growth Factor alpha/genetics/*pharmacology/physiology
EDAT- 2005/05/10 09:00
MHDA- 2005/10/05 09:00
CRDT- 2005/05/10 09:00
PHST- 2005/05/10 09:00 [pubmed]
PHST- 2005/10/05 09:00 [medline]
PHST- 2005/05/10 09:00 [entrez]
AID - 10.1002/bdra.20133 [doi]
PST - ppublish
SO  - Birth Defects Res A Clin Mol Teratol. 2005 Jun;73(6):447-54. doi: 
      10.1002/bdra.20133.