The carcinogenic potential of chemicals is currently evaluated with rodent life-time bioassays, which are time consuming, and expensive with respect to cost, number of animals and amount of compound required. For insight into early mechanisms of non-genotoxoc carcinogenesis and for identification of potential early biomarkers of non-genotoxic carcinogenesis, groups of rats were treated with a range of known non-genotoxic carcinogens for a period of 14, 28, or 90 days, and liver tissue was harvested for expression profiling. Control groups were treated with appropriate vehicles.
Overall design
Male Wistar rats were treated by oral gavage with different nongenotoxic hepatocarcinogens or non-hepatocarcinogens (Pioglitazone, Rosiglitazone) and corresponding vehicle controls. Depending on the administered compound, rats were treated daily for 14 or 28 days and sacrificed one day each after the last treatment for clinical chemistry analysis, histopathological evaluation and molecular profiling of the liver using Affymetrix RaGene_2.0_ST arrays.