PMID- 7669070
OWN - NLM
STAT- MEDLINE
DCOM- 19951012
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 50
IP  - 5
DP  - 1995 Aug 25
TI  - Diminished teratogenicity of retinoid X receptor-selective synthetic retinoids.
PG  - 669-76
AB  - One feature that contraindicates the wide therapeutic use of retinoids is their 
      teratogenicity. Synthetic retinoids are distinguishable from each other on the 
      basis of their partial or exclusive preference in binding and activation of 
      all-trans retinoic acid receptors (RARs) or retinoid X receptors (RXRs). Using 
      mouse embryo limb bud cells in micromass cultures as a bioassay, we examined the 
      inhibitory activities of a number of standard and novel retinoids on chondrogenic 
      cell differentiation. Transient cotransfection of HeLa cells was used to measure 
      the ability of each retinoid to induce transcription of a reporter gene by 
      activating RAR alpha, RAR beta, RAR gamma, or RXR alpha chimeric constructs. All 
      retinoids in this study that activated RARs to any degree in the cotransfection 
      assay also inhibited chondrogenesis in vitro, whereas retinoids that were either 
      specific for RXR or inactive in the cotransfection assay did not. The activity of 
      RAR-selective agonists and the inactivity of RXR-specific agonists in the 
      cotransfection assay correlated well with the relative teratogenicity of six of 
      the representative retinoids studied when orally administered at day 11 to 
      pregnant ICR mice.
FAU - Jiang, H
AU  - Jiang H
AD  - Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 
      Philadelphia, PA, USA.
FAU - Penner, J D
AU  - Penner JD
FAU - Beard, R L
AU  - Beard RL
FAU - Chandraratna, R A
AU  - Chandraratna RA
FAU - Kochhar, D M
AU  - Kochhar DM
LA  - eng
GR  - HD20925/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Teratogens)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Cartilage/drug effects/embryology
MH  - Female
MH  - HeLa Cells
MH  - Humans
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Pregnancy
MH  - Receptors, Retinoic Acid/*drug effects/metabolism
MH  - Retinoid X Receptors
MH  - Retinoids/metabolism/pharmacokinetics/*toxicity
MH  - Teratogens/metabolism/pharmacokinetics/*toxicity
MH  - Transcription Factors/*drug effects/metabolism
EDAT- 1995/08/25 00:00
MHDA- 1995/08/25 00:01
CRDT- 1995/08/25 00:00
PHST- 1995/08/25 00:00 [pubmed]
PHST- 1995/08/25 00:01 [medline]
PHST- 1995/08/25 00:00 [entrez]
AID - 0006-2952(95)00183-Z [pii]
AID - 10.1016/0006-2952(95)00183-z [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1995 Aug 25;50(5):669-76. doi: 10.1016/0006-2952(95)00183-z.