Induction of cleft palates: effects of triamcinolone acetonide on transcription in isolated nuclei.

The effect of triamcinolone acetonide on the transcriptional activity in nuclei isolated from maternal A/J mouse livers and embryonic maxillary processes (EMP) has been studied. Triamcinolone acetonide (TAC, 13 mg/kg body weight) was administered to A/J mice on day 12.5 of gestation, and the mice were sacrificed at different time periods following injection. We find a significant increase in transcription in liver nuclei, and a decrease in this activity in nuclei from embryonic maxillary processes in response to TAC at 16 to 20 hours following injection. With the drug alpha-amanitin we show that the effect of TAC on transcription in EMP cannot be due to fluctuations in the concentration of endogenous RNA polymerase B. This is further substantiated by studies on the transcription of EMP-nuclei in the presence of exogenous DNA template. Relative to controls, the data demonstrates that the concentrations of RNA polymerases A and B in EMP-nuclei remain unchanged in response to TAC. Conversely, stimulated liver nuclei result in significant increases in the concentrations of RNA polymerases A and B. We therefore propose that in embryonic maxillary processes TAC induces changes in the chromatin template which may interfere with normal development.