Polycyclic aromatic hydrocarbons (PAHs) constitute a large class of ubiquitous environmental pollutants formed after incomplete combustion of organic substances, such as coal, wood, charbroiled meat and at high levels in tobacco smoke. Benzo(a)pyrene (BaP), a representative PAH with potent carcinogenic properties, presents several biological and mutagenic effects, including DNA damage, reactive oxygen species (ROS) formation and alteration of transcription factor networks dynamics.
Hepatocellular carcinoma (HCC) accounts for 70-85% of all primary liver cancers worldwide, being regarded as one of the most lethal type of cancer due to its low survival rate. Although chronic inflammation due to viral infection with HB(C)V or alcohol consumption pose as the main risk factors, tobacco smoking is arising as a major risk factor for disease development.
Thus, this project aims to underline important transcriptomic alterations in in vitro hepatic models exposed to BaP and/or its main metabolites that may influence development and/or progression of HCC into a more malignant phenotype. The study will focus on results obtained from high throughput techniques (microarrays and RNA-seq) from different cell models (HepaRG, HepG2 and primary human hepatocytes) in order to identify important pathways and transcription factor networks related to the onset of BaP-induced hepatocarcinogenesis