Thierry Douki
SyMMES - INAC CEA, France
Title: Non-additive genotoxic effects of polycyclic aromatic hydrocarbons in mixtures in human in vitro models
Biography
Biography: Thierry Douki
Abstract
Non-additive genotoxic effects of polycyclic aromatic hydrocarbons in mixtures in human in vitro models
Polycyclic aromatic hydrocarbons (PAH) are ubiquitous pollutants found in food and urban atmospheres and associated with numerous professional occupations. One major health effect of PAH is their carcinogenic properties which result mostly from their ability to damage the genome. While parent PAH are not reactive, their metabolites damage biomolecules and in particular DNA through the formation of covalent adducts. These processes are well described for individual PAH, in particular benzo[a]pyrene (B[a]P). The genotoxic effects of mixtures of PAH have been less studied. In the recent years, we investigated the effects of synthetic mixtures and environmental extracts on hepatocytes, lung cells and skin explants. Emphasis was placed on the induction of phase I CYP450 mono-oxygenase genes and the formation of B[a]P-diol-epoxide (BPDE) adducts to DNA. In most cases, we observed lack of additivity, either synergy or inhibition, even in simple binary mixtures. In addition, a same mixture did behave the same way in different models, with synergy being frequent in hepatocytes and inhibition in lung cells and skin. Surprisingly, no correlation could be found between the induction of CYP genes, which is always larger with mixtures than with pure B[a]P and the extent of DNA damage. The bulk of these observations are in agreement with other data of the literature and show that the toxicity equivalency factor approach currently used for the prediction of risk is not optimal. New tools based on more sophisticated modelization are necessary.