Thierry Douki, Marie Carrière & Jean-Luc Ravanat

Toxic organic compounds are ubiquitous in the environment and are produced by many human activities. Exposure to such compounds is associated with the onset of diseases in humans. A first topic of interest in CIBEST is linked to air pollution and in particular the effects of polycyclic aromatic hydrocarbons (PAHs). This family of molecules is produced upon combustion of organic matter. It is thus present in the polluted atmospheres of cities because of emissions produced by traffic or heating. In addition, PAH are frequently found at high levels in some industries and represent a threat to workers. Our group is mostly interested in the genotoxic properties of PAH. Like many chemicals, the parent PAHs are poorly reactive and their toxic properties are mostly due to the production of reactive intermediates by the metabolic system in cells. Some of these metabolites reach DNA and covalently react with bases. The resulting compounds are DNA adducts which exhibit mutational properties. Our work aims at linking the parameters influencing the metabolic activity (cell type, mixture effects, etc.) and the damage to the genome.

Another line of research at CIBEST in the field of toxicity of organic compounds is related to warfare agents. We are in particular interest in vesicating agents such as sulfur mustard. Although this molecule was first used on the battlefield more than a century ago, it is still of interest nowadays. First, it continues to be used in military actions as recently in Syria or during the Iran-Iraq war. Sulfur mustard could also be used by terrorist. Indeed, it is quite easy to synthesize and significant stockpiles still exist. A last issue is the presence of old ammunitions that can lead to accidental exposure of civilians. In this field, CIBEST works in collaboration with the Biomedical Research Institute of Armies and The Defense Innovation Agency, and provides its analytical expertise. A first work was devoted to the quantification of DNA adducts in topically exposed animals. Temporal profiles of the damage to skin and internal organs were made, in relation with the extent of the wound. Currently, the work is oriented towards the quantification of specific biomarkers in biological fluids. The aim is to be able to quantify the extent of exposure in a group of individual and adapt the prophylactic response to apply.

It may last be mentioned that CIBEST has also developed tools to quantify DNA damage induced by organic compounds produced by endogenous processes like oxidative stress. For example, methods are available for the sensitive detection of exocyclic DNA adducts with the aldehyde resulting from lipid peroxidation. Other studies have involved the detection of adducts to glyoxal and methyl glyoxal.