Laboratory of genetic toxicology

 

Institut Pasteur de Lille
Director : Fabrice Nesslany

The genetic toxicology laboratory is a centre of excellence in France. In particular, it conducts studies to assess the genotoxic and mutagenic potential but also the endocrine disruption potential of many categories of substances.

With a very wide field of competence (human health, animal health, cosmetics, food, chemicals, plants/ vegetable, nanotechnologies, environment, etc.), the experts from the genetic toxicology laboratory have been cooperating with the pharmaceutical, cosmetics, food, chemical industries, etc.

The laboratory also participates in research programmes at a national and European level aimed at evaluating the genotoxic potential of atmospheric particles, manufactured nanoparticles, or even the endocrine disruption potential of the contaminants in our general environment, etc.

Laboratoire de toxicologie génétique

Presentation

Through our environment, our lifestyle and our diet, we are exposed to a large number of chemical and particulate contaminants whose impact on health, particularly during multi exposures, has yet to be characterized. Regarding air pollution, numerous epidemiological studies have recently highlighted the role of air quality on morbidity and mortality of respiratory origin. Anthropogenic air pollution appears to be responsible for an increase in the incidence and aggravation of respiratory diseases such as asthma, allergies or chronic obstructive pulmonary disease, and cancers. Other categories of substances raise questions about their potential toxicity, e.g., manufactured nanomaterials which have become part of our daily lives and whose effects are still poorly understood, or endocrine disruptors suspected of inducing health effects at low doses and/or cocktail effects, particularly in children and pregnant women, who are among the most sensitive populations.

As part of the university host team EA 4483 (IMPECS for IMPact de l’Environnement Chimique sur la Santé, i.e. IMPact of the Chemical Environment on Health), our laboratory aims at developing strategies for assessing the exposure, impregnation and health effects in humans of contaminants, and to identify the molecular and cellular mechanisms involved in their pathogenicity. Our team has recognized expertise in the field of genetic toxicology and endocrine disruption assessment.

Our objectives are to (i) highlight possible toxic, genotoxic and endocrine disrupting effects of contaminants, (ii) define possible synergies that would amplify the effects (“cocktail effects”) and (iii) develop new models to assess as early as possible these effects.

Transversal projects

  Study of the effects of mixtures of potentially Endocrine Disrupting substances

Our goal is to investigate the effects of mixtures of contaminants that are potential Endocrine Disrupting (ED) substances and representative of dietary exposure in France. We seek to identify the main mixtures of potential ED substances to which French people are exposed according to different types of diet in the infant and adult populations. We carry out in vitro tests providing data on main mechanisms and pathways of endocrine activity, in particular the binding affinity and activation of estrogen and androgen receptors, steroidogenesis, as well as tests for thyroid disruption.

Funding: ANSES. APR EST 2019

  Study of the possible potentiation of the effects of atmospheric contaminants

This research is being carried out within the framework of the “Pollution, Health and Longevity” Regional Pole. The first objective is to collect a large number of atmospheric aerosols representative of different urban environments and to characterize them on a physicochemical level in order to identify the components of particulate matter (PM) and to determine their variability. Our objective is to define the major drivers of the toxicity of these atmospheric aerosols and to investigate which particulate and chemical contaminants have the most “weight” in their toxicity. The possible potentiation of toxic effects will be investigated. We will evaluate the combinations of contaminants (chemical-chemical and/or chemical-particulate) presenting particularly harmful effects.

  Developing new models

This project aims at validating an innovative 3D model of human hepatocytes for the analysis of genotoxicity related to chemical-induced human hepatocarcinogenesis. The objective is to implement in vitro models of 3D hepatocyte spheroid cultures and to compare these in vitro results with those obtained in standard in vivo genotoxicity tests in order to eventually replace the animal model.

Funding: Inserm. Plan Cancer 2014-2019. ITMO Cancer d’Aviesan. Funding Call – « New Experimental Models » 2019.

Members

Fabrice NESSLANY
Head of laboratory, Expert Toxicologist

Sophie SIMAR
Assistant

Hélène MOCHE
Assistant

Anne PLATEL
Associate professor, Univ Lille

Aurélie RIZZA
Quality Assurance Manager

Martine SOCKEEL
Secretary

Ludovic HUOT
Engineer

Frédérique LOBEZ
Assistant

Doris LAGACHE
Assistant

Smail TALAHARI
Assistant

Gonzague DOURDIN
Technician

Eulalie GATEAU
Technician

Florent TIBERGHIEN
Technician

Éric VERCAUTEREN
Technician

Valérie VERNIEUWE
Maintenance worker

Publications

Fessard V, Nesslany F.
From Basic Research to New Tools and Challenges for the Genotoxicity Testing of Nanomaterials.
Nanomaterials (Basel). 2020 Oct 20;10(10):2073.

Jalili P, Huet S, Lanceleur R, Jarry G, Le Hegarat L, Nesslany F, Hogeveen K, Fessard V.
Genotoxicity of Aluminum and Aluminum Oxide Nanomaterials in Rats Following Oral Exposure.
Nanomaterials (Basel). 2020 Feb 11;10(2).

Wang Y, Sauvat A, Lacrouts C, Lebeau J, Grall R, Hullo M, Nesslany F, Chevillard S.
TiO2 Nanomaterials Non-Controlled Contamination Could Be Hazardous for Normal Cells Located in the Field of Radiotherapy.
Int J Mol Sci. 2020 Jan 31;21(3).

Platel A, Privat K, Talahari S, Delobel A, Dourdin G, Gateau E, Simar S, Saleh Y, Sotty J, Antherieu S, Canivet L, Alleman LY, Perdrix E, Garçon G, Denayer FO, Lo Guidice JM, Nesslany F.
Study of in vitro and in vivo genotoxic effects of air pollution fine (PM2.5-0.18) and quasi-ultrafine (PM0.18) particles on lung models.
Sci Total Environ. 2020 Apr 1;711:134666.

Saleh Y, Antherieu S, Dusautoir R, Y Alleman L, Sotty J, De Sousa C, Platel A, Perdrix E, Riffault V, Fronval I, Nesslany F, Canivet L, Garçon G, Lo-Guidice JM.
Exposure to Atmospheric Ultrafine Particles Induces Severe Lung Inflammatory Response and Tissue Remodeling in Mice.
Int J Environ Res Public Health. 2019 Apr 4;16(7).


Keywords

Genotoxicity ; Mutagenesis ; Atmospheric pollution ; Nanomaterials ; Endodrin disruptors ; Cocktail effects

Team contact

Fabrice Nesslany
Head of toxicology service

fabrice.nesslany@pasteur-lille.fr
03 20 87 72 72