Renal gene expression changes in p53 heterozygous and p53 homozygous mice due to chronic dietary exposure to the mycotoxin ochratoxin A

Changes in renal gene expression were assessed in p53WT(+/+) mice and their heterozygous p53TG(+/-) counterparts exposed to the nephrotoxic and tumourigenic fungal toxin Ochratoxin A (OTA) in their diet for 26 weeks. The p53TG mouse model has been used in screening for potential carcinogens as it displays increased sensitivity to genotoxic carcinogens. Comparison between the effects of OTA in diet on male mice of these two strains was assessed at 0, 0.05, 2.0, 10.0 mg OTA/kg diet. Changes in global gene expression were compared using Agilent Mouse oligonucleotide microarray analysis of kidneys from control (0 mg OTA/kg diet) and treated (2 mg OTA/kg diet) mice. Significant changes in gene expression associated with cell cycle regulation, DNA damage repair, tumour suppression and apoptosis were consistent with nephrotoxicity due to OTA exposure in both mouse strains. Changes in genes related to oxidative stress and free radical scavenging may contribute to the down-regulation by OTA of genes associated with metabolism. Gene expression changes were consistent with phenotype and provided insight on the cellular responses to chronic OTA exposure. Kidneys from male p53WT mice and their heterozygous p53TG counterparts were collected at terminal necropsy from control mice and mice exposed to 2 mg OTA/kg diet for 26 weeks.