ToxEMAC / ABTE Team

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ToxEMAC / ABTE Team
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ToxEMAC / ABTE Team
ToxEMAC / ABTE Team
+33(0)2 31 45 51 93

The team

SICHEL François, Pr
Directeur de l’UR ABTE – ToxEMAC
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Spécialité

  • Toxicologie

Fonctions exercées au CFB

  • Chercheur

Domaines d’expertise

  • Toxicologie génétique des polluants aériens ;
  • Toxicité de l’hadronthérapie ;
  • Porteur du parcours de Master pro « Développement Clinique du Médicament ».

Enseigne

Au niveau local et régional :

  • UFR Santé de l’Université de Caen-Normandie :
    • Faculté des sciences pharmaceutiques: Professeur d’université (PU) en toxicologie intervenant dans les cursus pharmaceutiques :
      • Master “Développement Clinique du Médicament” ;
      • Master “Qualité des Aliments et Innovation Santé” ;
      • Master “Gestion des Risques Environnementaux” (à l’Université du Havre).

Membre de…

Au niveau régional :

  • Cancéropôle Nord-Ouest, axe 1 (médecine de précision des tumeurs solides) ;
  • Archade ;
  • Co-coordinateur de l’axe « sécurité sanitaire, aliments durables » du pôle CBSB de la COMUE Normandie Université.

Au niveau national :

  • Société Française de Toxicologie Génétique (SFTG)(vice-président) ;
  • Société Française de Toxicologie (SFT) ;
  • Réseau national de recherche pré-clinique en radiothérapie (RAdioTransNet) ;
  • Groupement Associé des enseignants de toxicologie (GATOX)

Au niveau international :

  • European Environmental Mutagenesis and Genomics Society (EEMGS)
SICHEL François, Pr
ToxEMAC / ABTE
+33(0)2 31 45 51 93

The ToxEMAC (Environmental Toxicology, Aerial environments and Cancer) team, attached to the ABTE EA4651 Research Unit, is shared between the Caen and Rouen University Health departments. Within its research building, it hosts 11 lecturing researchers, 1 researcher, 2 technicians and 9 PhD students, and also includes 2 radiation oncologists from the Centre François Baclesse.

Research activity

The ToxEMAC ABTE team’s research focuses on 3 themes:

1/ Lung toxicity of chemical and particle pollutants
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  • Head researcher:Véronique André

The aims of this research theme are to characterise toxicity (pro-inflammatory and genotoxic effects) of chemical and particle pollutants: outdoor aerosols  associated with combustion processes (road traffic, pyrotechnic activities, industrial fires) and professional and medical exposure (dust, carer contamination by anticancer drugs). Collaboration with the university hospitals in Caen and Rouen enable us to target professional groups with high exposure to carcinogenic substances and for which exposure markers could be proposed to better evaluate their exposure and/or to determine the impact of protective measures.

2/ Bioaerosols, fungal biodiversity, health
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  • Head researcher: David Garon

This theme focuses on bioaerosols and their impact on health. Work aims at incrementing a database on ‘deteriorated habitats’ in order to determine exposure thresholds to mold beyond which clinical symptoms are observed. The effects of climatic factors on the growth and virulence of fungal species that are recurrent in indoor environments are also studied. Several parameters, such as growth, adherence, expression of genes implied in the biosynthesis of potentially carcinogenic mycotoxins such as sterigmatocystin (CIRC 2B), pulmonary and cutaneous cytotoxicity are studied. In order to grasp and better understand the complexity of bioaerosols, we work via multidisciplinary approaches.

We also work with the centre’s operational hygiene team within the context of fungal and infectious risk prevention in hospital settings, in particular within the framework of demolition/reconstruction work at the CHU in Caen.

3/ Toxicity associated with irradiation of healthy tissue
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  • Head researcher: Carine Laurent

Within the framework of the ARCHADE programme (ESPRITS, ToxIP3, PAESCART, PBS-BIO projects), our research work aims at evaluating toxicity to healthy tissue during proton therapy combined or not with innovative treatment such as DDR inhibitors (DNA Damage Response) on murine models; to search for predictive markers of the response of healthy tissue to irradiation in blood in patients treated by conventional radiotherapy or by proton therapy at the centre; to propose clinical study protocols according to obtained results and in association with radiotherapists integrated within the team. Obtained results are aimed at developing combined treatment adapted to patients treated by the S2C2 PBS proton beam at the ARCHADE facility.

Technical resources

  • Cell culture laboratories (2)
  • Air-liquid interface cell exposure system (2020)
  • Fungal microbiology laboratory and mycobank (over 2,000 isolates) (2007)
  • Motorised plateau epifluorescence microscope and automatic analysis system for genotoxicity tests (micronuclei, Comet Assay, gH2AX focus) (Metasystem) (2018)
  • Hot laboratory for post-marking
  • uHPLC-CPG-HRMS Waters system (2019)
  • Biochemistry and molecular biology laboratory (microplate reader, PCR, qPCR, etc.)
  • Climate chambers
  • Cryogenic freezer
  • EREM (Expertise, Acknowledgments and Studies in Mycology) expertise cell, University faculty of health

Results

Scientific activity by the members of the ToxEMAC team has, since 2015, led to 100 international publications, including 19 scientific journals. The team has multiplied its research contracts which include 16 projects as coordinator and 7 projects as partner. The most noteworthy results are as follows:

Clinico-biological integration in hadrontherapy: radiotherapy toxicity on healthy tissue

The PAESCART programme investigated blood biomarkers in order to predict delayed cutaneous side effects after radiotherapy. This research work demonstrated that the irradiated blood of the most radiosensitive patients presented ex vivo decreased apoptosis and lymphocyte microneclei frequency, together with markers of oxidative stress and inflammation. The ESPRITS programme (side effects of proton therapy associated with irradiation of healthy tissue) associating the centre’s departments of radiotherapy and medical physics, in collaboration with the Institut Curie, demonstrated a difference in response in healthy tissue (skin, lungs, heart) depending on proton irradiation modalities.

New models of genotixicity biomarkers for the study of aerial pollutants

Research work focusing on the toxicity of aerial pollutants has led to two new advances: the development of in vitro approaches at the air-liquid interface, to characterise the genotoxicity of atmospheric particles on pulmonary models, and analytical perfecting for the detection of DNA lesions associated with exposure to aerial contaminants. We have validated an original liquid chromatography method coupled with mass spectrometry, and enabling the measurement of 9 exocyclic adducts derived from 8 aldehydes.

Implementation of a ‘deteriorated habitat’ database

The MOLD AIR study, which benefited from support from the ADEME and ARS, enabled external partners to be federated (Hygiene departments at the Caen, Lisieux, Cherbourg Councils and the Calvados CAF – Family Allowance Agency, etc.) around the question of residential properties contaminated by mold, and its impact on health. This network enabled us to implement an air sampling campaign in mold-deteriorated homes, on which microbiological and toxicological characterisation of collected bioaerosols and fungal isolates was performed. A database of ‘deteriorated habitats’ was therefore compiled, and continues to be incremented to allow statistical studies aimed, in particular, at establishing a relationship between resident symptoms and data from mycological and toxicological analyses. This database also enables the study of fungal species collected in indoor environments (Aspergillus versicolor in particular) with carcinogenic properties.

Partnerships

At regional level
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  • Cancéropôle Nord-Ouest,
  • SéSAD theme – COMUE Normandy-University (LMSM, U2RM, PBS-BRICS laboratories in the Universities of Caen and Rouen),
  • CETAPS Laboratory (University of Rouen),
  • Dermatology department, Microbiology Laboratory and Pharmacy CHU Caen,
  • Department of Professional Medicine CHU Rouen,
  • SFR ICORE.
At national level
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  • Medical physics department at the Proton Therapy Centre in Orsay,
  • RadeXP platform (Institut Curie, Proton Therapy Centre, Orsay),
  • INSERM U1196/UMR9187 CMIB (Institut Curie-Orsay),
  • LCIB (UMR E3 CEA-UJF, Grenoble),
  • IRSET (INSERM 1085, Rennes),
  • LECA UMR 5553 (Grenoble),
  • UCEIV EA4492 (University of the Littoral Opal Coast, Dunkirk),
  • GRITA EA7365 (University of Lille),
  • CSTB,
  • ANSES.
At international level
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  • University hospital, Liège,
  • KNUCA University, Kiev,
  • Lebanese University, Beirut,
  • National Centre of Traditional Medicine, Cambodia.
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