Study of the 16 EU-JECFA PAHs interaction with the aryl hydrocarbon receptor (AhR) using rat and human reporter cell lines

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are toxic environmental and food contaminants which are formed during the incomplete burning of organic substances. They are widely dispersed in the environment due to domestic and industrial activities as wood, coal, oil, gas combustions or industrial garbage burning. Moreover, these compounds are formed by foodstuff transformation processes (i.e. cooking, drying or smoking processes) which can contribute to the main source of human contamination as well as cigarette smoking. Polycyclic aromatic hydrocarbons are well-known as carcinogenic, mutagenic and genotoxic compounds. Many studies have demonstrated the different toxicological pathways of the PAHs. One of them is the cellular aryl hydrocarbon receptor (AhR) activation which can be evaluated with the in vitro CALUX bioassay (Chemically Activated LUciferase gene eXpression). However, several studies have reported that the AhR activation is tissue and species dependant. In this study, we evaluated and compared the AhR-activation by the 16 priority PAHs of the list proposed by the European Union and the Joint FAO/WHO Expert Committee on Food Additives (EU-JECFA) . We used four different recombinant reporter gene cell lines: two human hepatoma (HEPG2-Luc-ULg) and mammary carcinoma (T47D-Luc-ULg) cell lines and two rat hepatoma cell lines (H4IIE-Luc-BDS, H4IIE-Luc-ULg), which differ either by the tissue or the species they originate from, either by the promoter of the reporter gene expression vector. As benzo(a)pyrene (BaP) is the PAH reference compound, the BaP relative response potency (REP) of each compound was evaluated and these REP values were compared with the Toxic Equivalent Factor (TEF) values already established for several PAHs.