Title: Comparison of the CALUX bioassay and ID-HRGC/HRMS as measures of dioxin toxic equivalents in serum

Auteur(s): Warner M ; Eskenazi B ; Patterson DG ; Clark G ; Turner WE ; Bonsignore L ; Mocarelli P ; Gerthoux PM ;  ; 

Year: 2003

Journal: Organohalogen Compounds

Subject(s): bioassay ; CALUX ; dioxin ; equivalent ; polychlorinated ; polychlorinated dibenzo-p-dioxins ; TCDD ; PCBs ; PCB ; polyhalogenated aromatic hydrocarbons ; dioxin-like compounds ; environment ; TEQ ; dioxins ; clean-up ; Human serum ; analysis ; Luciferase ; gene expression ; validation ;  ; 

Summary: Polychlorinated dibenzo-p-dioxins (PCDDs) including 2,3,7,8, tetrachlorodibenzo-p-dioxin (TCDD), dibenzofurans (PCDFs), and biphenyls (PCBs) constitute a group of polyhalogenated aromatic hydrocarbons that are persistent and widespread environmental contaminants. Since TCDD and other dioxin-like compounds exist as complex mixtures of various congeners throughout the environment, calculating total TCDD toxic equivalent (TEQ) concentrations has become widely accepted as the most relevant exposure measure in studies of health effects of dioxins and dioxin-like compounds. In particular, in background-exposed populations, these other congeners may contribute a large portion of TEQ relative to TCDD. To date, analytical methods to quantify exposure to these chemicals in biologic samples have included very sensitive and specific techniques such as high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). However, these methods are time-consuming and expensive, require large sample volumes and extensive sample clean-up. An AhR-dependent recombinant bioassay was developed that reportedly can measure the total TEQ concentration of a complex mixture in human serum, without extensive cleanup and chemical analysis procedures. It requires a relatively smaller volume of serum (<5ml) and less time to complete. The chemical-activated luciferase gene expression (CALUX) bioassay measures the ability of a chemical mixture to activate AhR-dependent gene expression in cells in culture. It is based on AhR-mediated firefly luciferase expression in genetically modified cell lines. To date, limited validation studies of the CALUX results against HRGC/HRMS measurements have been completed. Despite this, the CALUX bioassay has already found application in studies of health outcomes. The purpose of this study is to examine the validity of the CALUX bioassay to measure TEQ in a background-exposed population. We compare the CALUX-TEQ with the 'gold standard' WHO-TEQ, derived from Isotope Dilution-HRGC/HRMS measurements in a sample of Italian women.