PMID- 16322074
OWN - NLM
STAT- MEDLINE
DCOM- 20060330
LR  - 20181224
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 90
IP  - 1
DP  - 2006 Mar
TI  - Retinoid receptor antagonists alter the pattern of apoptosis in organogenesis 
      stage mouse limbs.
PG  - 208-20
AB  - Exposure of murine limbs in vitro to vitamin A (retinol) induces limb reduction 
      defects and apoptosis. To assess the relative roles of the retinoic acid 
      receptors (RARs) and the retinoid X receptors (RXRs), embryonic-day-12 murine 
      limbs were cultured with selective RAR or RXR antagonists in the presence or 
      absence of teratogenic concentrations of retinol. Both antagonists alone impaired 
      limb development; in the presence of teratogenic concentrations of retinol, both 
      attenuated limb malformations. Abnormal limb morphology, whether caused by 
      excessive or attenuated retinoid signaling by retinol or either antagonist, 
      respectively, was correlated with increased apoptosis after 24 h of drug 
      exposure. We conclude that, in the developing limb, antagonists selective for 
      either member of the RAR/RXR heterodimer attenuate retinoid signaling and block 
      the teratogenic signaling of excess retinol. Improvements in limb morphology in 
      the presence of either the RAR or the RXR antagonist coincided with restoration 
      of the extent and localization of limb bud apoptosis to control patterns.
FAU - Ali-Khan, Sarah E
AU  - Ali-Khan SE
AD  - Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, 
      Canada H3G 1Y6.
FAU - Hales, Barbara F
AU  - Hales BF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051201
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Teratogens)
RN  - 11103-57-4 (Vitamin A)
RN  - M531IV9E0V (BMS453)
SB  - IM
MH  - Abnormalities, Drug-Induced/metabolism
MH  - Animals
MH  - Apoptosis/drug effects/*physiology
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Fetal Development
MH  - *Limb Buds/abnormalities/drug effects/metabolism
MH  - Limb Deformities, Congenital/chemically induced/*metabolism/pathology
MH  - Mice
MH  - Organogenesis/drug effects/*physiology
MH  - Receptors, Retinoic Acid/antagonists & inhibitors/*metabolism
MH  - Retinoid X Receptors/antagonists & inhibitors/*metabolism
MH  - Retinoids/pharmacology
MH  - Teratogens/toxicity
MH  - Vitamin A/toxicity
EDAT- 2005/12/03 09:00
MHDA- 2006/03/31 09:00
CRDT- 2005/12/03 09:00
PHST- 2005/12/03 09:00 [pubmed]
PHST- 2006/03/31 09:00 [medline]
PHST- 2005/12/03 09:00 [entrez]
AID - kfj060 [pii]
AID - 10.1093/toxsci/kfj060 [doi]
PST - ppublish
SO  - Toxicol Sci. 2006 Mar;90(1):208-20. doi: 10.1093/toxsci/kfj060. Epub 2005 Dec 1.