2CdA intervention with PK11195

In this time course pregnant CD-1 (outbred) dams were exposed to the 2-chloro analogue of 2'-deoxyadenosine (a metabolic toxin) on 8 d.p.c. The test dose of 2.5 mg/kg 2CdA was modeled for a 5% increased risk of microphthalmia in term fetuses. Exposed embryos were co-treated with PK11195, a nontoxic ligand of the mitochondrial peripheral-type benzodiazepine receptor (Bzrp) that effectively blocks p53 protein induction and developmental toxicity induced with 2CdA. Sampling intervals were anchored to the conditional biomarker (p53 protein induction) expressed in 2CdA-treated embryos between 3.0- and 4.5h post-exposure. Since p53 protein induction has been defined as a critical event in 2CdA-induced microphthalmia, these sampling intervals represent times before (3.0h), during (4.5h), and after (6.0h) this critical event. No p53 induction is observed in embryos co-treated with 2CdA and PK11195. All measurements were on RNA from the embryonic headfold. Keywords = time series Keywords = 2-chloro-2'-deoxyadenosine Keywords = PK11195 Keywords = embryo Keywords = p53 protein induction Keywords = microphthalmia Keywords: time-course