Hepatic premalignant alterations triggered by human carcinogen aristolochic acid I in canines

Ten-month-old male beagle canines were purchased from the ANNIMO Science and Technology Ltd (Nanjing, China, Certificate No. SCXK (Su) 2010-0002), and maintained in a specific pathogen-free environment. Canines were randomly assigned to two groups (4 in each group) and received capsules with control filler or Aristolochic Acid I (AAI) filler (3 mg/kg/day, equivalent dose of mouse) for 10 days. Canines were sacrificed at 11 days after initiation of the treatment. Livers were excised immediately after sacrifice. Part of the livers were immediately snap-frozen in liquid nitrogen and kept at -80°C for total RNA isolation and microRNA microarray analysis. In this study, liver samples from eight canines were used to acquire the miRNA expression profiling and the function of the abudant miRNAs were analyzed by bioinformatic methods. AAI-induced dysregulation of let-7 and miR-23a clusters were closely associated with c-Myc and IL-6R signaling.