Mechanisms of Pancreatic Acinar Cell Neoplasia Associated with Gene Expression Changes caused by Dietary Exposure of Rats to Ammonium perfluorooctanoate, Wyeth 14,643 or Diethylhexyl phthalate
To identify putative procarcinogenic gene changes associated with pancreatic acinar cell neoplasia in rats exposed to peroxisome proliferator activated receptor alpha agonists, we performed transcription profiling in the pancreas of rats fed diets containing the pancreatic carcinogen Wyeth 14,643 (Wy) at procarcinogenic (50ppm) and non-carcinogenic (20ppm) doses for 1, 7, 28 and 90 days. The effects of these treatments were compared to those of ammonium perfluorooctanoate (APFO) 300 ppm, an agent shown to induce pancreatic acinar cell adenomas in rats, and diethylhexylphthalate (DEHP) 12,000 ppm, an agent not shown to produce pancreatic acinar cell tumors. To assess whether this putative mechanism(s) of carcinogenesis occurs in ‘target’ cells we have also performed transcriptional profiling in isolated pancreatic acinar cells obtained from animals exposed to these compounds in vivo.
Overall design
Treatment-induced changes in gene expression were assessed in the pancreas by two-colour hybridisation of fluorescently labelled (Cy5/Cy3) cRNAs from three separate animals for each treatment against cRNA generated from a common ‘reference’ (control) made by pooling pancreatic RNA samples extracted from control (vehicle-treated) animals. Two hybridisations were performed in duplicate in order to incorporate a ‘dye swap’. Hence, there were 5 arrays per treatment group.
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