Aug 30, 2016
Mixtures effects in the genotoxicity of pollutants: when 1+1 is not 2
Contact : Thierry Douki
Mixtures effects in the genotoxicity of pollutants: when 1+1 is not 2

Scheme of the study and investigated effects.

Combustion of organic matter (engine exhaust, urban heating, etc.) produces some toxic and carcinogenic compounds known as Polycyclic Aromatic Hydrocarbons (PAH). After metabolization in cells they become reactive and can modify DNA. Numerous work have studied PAH as individual products. The data obtained are interesting but do not reflect the real conditions. As a matter of fact, PAHs are always produced in complex mixtures and all PAH interact with cellular metabolism enzymes. This may lead to inhibition or synergistic effects. At INAC, the LAN team, in collaboration with Grenoble hospital, has compared the DNA damage induce by the most carcinogenic PAH, Benzo[a]pyrene (B[a]P), alone or in complex mixture mimicking environmental sources. The metabolic activities were found to be weaker and the amount of DNA damage lower when lung cells were exposed to mixtures than to pure B[a]P. These results contrast with previous results obtained by the team showing that in hepatocytes, liver cells, the mixtures exhibited a synergistic effects on the formation of B[a]P-mediated damage to DNA. These results show the difficulty to assess the risk associated with exposure to complex polluted atmospheres. The risk depends on the composition of the mixture and the organ of interest. Modelization will likely be a way to consider the interaction between the chemicals and make safe prediction. However, much more experimental data are needed.

This work was co-funded by CEA and Ademe.


Inhibition of the formation of benzo[a]pyrene adducts to DNA in A549 lung cells exposed to mixtures of polycyclic aromatic hydrocarbons, C. Genies, A. Jullien, E. Lefebvre, M. Revol, A. Maitre and T. Douki, Toxicol. In vitro 2016.



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