Molecular interactions between Vitamin A and PCB-77 induced phase I and II biotransformation pathways in Atlantic salmon (Salmo salar)

Active derivatives of vitamin A are essential in physiological processes including cell growth, differentiation, morphogenesis and development. Aryl hydrocarbon receptor (AhR) agonists such as planar halogenated aromatic hydrocarbons (HAHs) are known to interfere with these processes by mediating increased metabolism vitamin A. To investigate interactions between vitamin A and AhR pathways in fish systems, groups of juvenile Atlantic salmon (salmo salar) were treated singly and also in combination with 0 (control), 0.1, 1 and 10 mg/kg of retinoic acids (RA) and one concentration, 0.1mg/kg of PCB-77 and divided into one dose-response and one time-dependent study. Liver samples were collected at day 5, 8, 12 and 19 and analyzed for gene expression using RT-PCR. Dose response analysis shows down regulation of RARa with increasing RA concentration and slight up-regulation with combined exposure with PCB-77. The AhRa and AhRb were not affected with single RA treatment; however, AhR_ was down-regulated when fish were exposed to both compounds. CYP1A shows increased gene expression with both increasing RA treatment and combined exposure with PCB-77. Analysis of gene expression for AhRa, AhRb, RARa, UDPGT, GST and CYP1A in combined exposure conditions showed a time-specific gene expression pattern indicating a consistent down-regulation of gene expression at day 12 post-exposure. Despite that enzymatic activity analysis for phase I and II enzymes are still pending, the gene expression data show a complex pattern of interaction between vitamin A and the weak AhR agonist (PCB-77) on phase I and II genes, and retinoic acid receptor and need to be studied in more details.