In the recent years, atmospheric pollution has emerged as a major health issue. Polycyclic aromatic hydrocarbons (PAH) are a class of pollutants associated with vehicle exhausts, urban heating and industries using coal and oil derivatives. More than 100 PAH have been identified and they are always produced in complex mixtures. The ability of PAH at damaging DNA makes them mutagenic and carcinogenic. In order to better understand the mechanisms leading to DNA modification, we undertook a study involving human cell lines representative of target organs (lungs and bladder). We showed that formation of covalent adducts was the major damaging pathway. More interestingly, we observed that the formation of adducts in lung cells was larger at low than at high concentration of benzo[a]pyrene (B[a]P), the most toxic PAH. Accordingly, mixture of B[a]P with other PAH leads to a decrease in the level of adducts compared to pure B[a]P. This unexpected result was explained by the metabolization properties of lungs cells which require a threshold amount of PAH to achieve the full induction of the protective proteins. These observations illustrate the difficulty to predict the toxicity of mixture of compounds. The general approach using “toxic equivalent factors” is based on additive effects but does not consider potentialization of inhibitory effects as observed with PAH. More sophisticated models requiring more experimental data are needed.
C. Genies, A. Maître, E. Lefèbvre, A. Jullien, M. Chopard-Lallier & T. Douki (2013) The extreme variety of genotoxic response to benzo[a]pyrene in three different human cell lines from three different organs, PLOS One, accepted.
Last update : 10/09 2013 (863)