EFFECTS OF BENZO[K]FLUORANTHENE ON PROTEOSYNTHESIS AND SELECTED METABOLIC GENES IN A MODEL OF IMMORTALIZED HUMAN HEPATOCYTES.

Polyaromatic hydrocarbons (PAHs) are a diverse group of environmental and dietary contaminants. PAHs are primarily metabolized through the aryl hydrocarbon receptor (AhR)-regulated enzymatic pathway. Both parent PAHs and their metabolites may exert various types of toxicity in target cells and tissues. In addition to their wellknown genotoxic (and carcinogenic) effects, PAHs may alter numerous additional cellular events, including cell metabolism. In this project, we study whether strong AhR ligand benzo[k]fluoranthene (BkF) can modulate genes associated with glucose and lipid metabolism, as well as proteosynthesis, which is essential metabolic process performed at high energetic cost. We used an in vitro model of immortalized human hepatocytes, MIHA cell line. We observed a significant suppression of proteosynthesis induced by BkF in MIHA cells, as determined by the SUnSET method. We also observed a moderate deregulation of several genes associated with further evaluated metabolic processes. Based on this, we continue to evaluate possible impact of strong AhR ligands, such as BkF, on cellular metabolism, as well as functional role of this transcription factor in the complex effects of PAHs on cellular metabolism. [ABSTRACT FROM AUTHOR]