ToxEMAC / ABTE team

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ToxEMAC / ABTE team
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ToxEMAC / ABTE team
ToxEMAC / ABTE team
02 31 45 51 93

The team

SICHEL François, Pr
Director, UR ABTE - ToxEMAC
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Speciality

  • Toxicology

Positions held at the CFB

  • Researcher

Areas of expertise

  • Genetic toxicology of airborne pollutants;
  • Hadrontherapy toxicity ;
  • Sponsor of the "Clinical Drug Development" Master's program.

Sign

Local and regional :

  • UFR Santé de l'Université de Caen-Normandie :
    • Faculty of Pharmaceutical Sciences: University Professor (PU) in Toxicology for pharmaceutical courses:
      • Master's degree in Clinical Drug Development;
      • Master's degree in Food Quality and Health Innovation;
      • Master's degree in Environmental Risk Management (at the University of Le Havre).

Member of...

At regional level :

  • Cancéropôle Nord-Ouest, axis 1 (precision medicine for solid tumors) ;
  • Archade;
  • Co-coordinator of the "food safety, sustainable food" axis of the CBSB cluster of the COMUE Normandie Université.

At national level :

  • Société Française de Toxicologie Génétique (SFTG)(vice-president) ;
  • French Society of Toxicology (SFT) ;
  • National pre-clinical radiotherapy research network (RAdioTransNet) ;
  • Associated Group of Toxicology Teachers (GATOX)

Internationally :

  • European Environmental Mutagenesis and Genomics Society (EEMGS)
SICHEL François, Pr
ToxEMAC / ABTE
02 31 45 51 93

The ToxEMAC team (Toxicology of the Environment, Airborne Environments and Cancer), attached to the UR ABTE EA4651, is shared by the UFR Santé of Caen and Rouen. The research building houses 11 teacher-researchers, 1 researcher, 2 technical staff and 9 PhD students, as well as 2 of the Center's radiotherapists.
It specializes in toxicology, radiobiology, fungal microbiology and hygiene, biochemistry and analytical chemistry.

Research activity

The research activity of ABTE's ToxEMAC team focuses on 3 areas:

1/ Pulmonary toxicity of chemical and particulate pollutants
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  • Manager: Véronique ANDRE

The objectives of this axis are to characterize the toxicity (pro-inflammatory and genotoxic effects) of chemical and particulate pollutants: outdoor air aerosols linked to combustion processes (road traffic, pyrotechnic activities, industrial fires) and occupational and medical exposures (dusts, contamination of carers by anticancer drugs). Collaborations with the Rouen and Caen university hospitals enable us to target groups with high occupational exposure to carcinogenic substances, for whom exposure markers could be proposed to better assess their exposure and/or the impact of protective measures.

2/ Bioaerosols, fungal biodiversity and health
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  • Manager: David GARON

This area focuses on bioaerosols and their impact on health. Work is underway to increment a database of "degraded habitats" in order to determine mold exposure thresholds above which clinical symptoms are present. The effects of climatic factors on the growth and virulence of recurring fungal species in indoor environments are also being studied. Several parameters such as growth, fungal adhesion, expression of genes involved in the biosynthesis of potentially carcinogenic mycotoxins such as sterigmatocystin (IARC 2B), pulmonary and cutaneous cytotoxicity are being monitored. To better understand the complexity of bioaerosols, we use multidisciplinary approaches.

We are also working with the Centre's operational hygiene team (EOH) on the prevention of fungal and infectious risks in the hospital environment, particularly in the context of demolition/reconstruction work at Caen University Hospital.

3/ Toxicity linked to irradiation of healthy tissue
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  • Manager: Carine LAURENT

As part of the ARCHADE program (ESPRITS, ToxIP3, PAESCART, PBS-BIO projects), our work aims to assess the toxicity to healthy tissue of proton therapy combined or not with innovative treatments such as DDR (DNA Damage Response) inhibitors in mouse models; search for predictive markers of the response of healthy tissues to irradiation in the blood of patients treated with conventional radiotherapy or proton therapy at the Center; propose clinical study protocols based on the results obtained and in liaison with the team's radiotherapists. The results obtained will be used to develop combination treatments for patients treated with the PBS proton beam from ARCHADE's S2C2 facility.

Technical resources

  • Cell culture laboratories (2)
  • Air-liquid interface cell exposure system (2020)
  • Fungal microbiology laboratory and mycotheque (over 2,000 isolates) (2017)
  • Epifluorescence microscope with motorized stage and automatic analysis system for genotoxicity tests (micronuclei, comet assay, gH2AX foci)("Metasystem") (2018)
  • Hot lab for post-marking
  • Waters uHPLC-CPG-HRMS system (2019)
  • Biochemistry and molecular biology laboratory (microplate reader, PCR, qPCR, etc.)
  • Climatic chambers
  • Freezer
  • EREM expertise unit (Expertises, Reconnaissances et Etudes en Mycologie), UFR Santé

Results

The scientific activity of ToxEMAC team members has resulted in 100 international publications since 2015, including 19 journals. The team has multiplied its research contracts, including 16 projects as project leader and 7 as partner.
The most significant results are presented here:

Clinical-biological integration in hadrontherapy: toxicity of radiotherapy on healthy tissue

The PAESCART program investigated blood biomarkers to predict late cutaneous side effects after radiotherapy. This work showed that the most radiosensitive patients showed a decrease in apoptosis and lymphocyte micronuclei frequency in their ex vivo irradiated blood, as well as changes in markers of oxidative stress and inflammation. The ESPRITS (Effets Secondaires de la PRotonthérapie liés à l'Irradiation des Tissus Sains) program, involving the Center's radiotherapy and medical physics departments in collaboration with the Institut Curie, showed a difference in the response of healthy tissues (skin, lungs, heart) according to proton irradiation modalities.

New genotoxicity models and biomarkers for studying airborne pollutants

Work on the toxicity of airborne pollutants has seen two new advances: the development of in vitro approaches at the air-liquid interface to characterize the genotoxicity of atmospheric particles in lung models, and analytical developments for the detection of DNA lesions linked to exposure to airborne contaminants. We validated an original liquid chromatography-mass spectrometry method for the determination of 9 exocyclic adducts derived from 8 aldehydes. Adduct profiles were then characterized in the DNA of white blood cells collected from smokers and non-smokers as part of a study conducted in collaboration with the tobaccology department of Liège University Hospital. Significant differences in adduct levels were observed between smokers and non-smokers, a highly promising result which will enable us to investigate the role of aldehydes in lung carcinogenesis.

Setting up a "degraded habitats" database

The MOLD AIR study, supported by ADEME and ARS, brought together partners in the field (Health Departments of the cities of Caen, Lisieux, and Cherbourg, CAF du Calvados, etc.) to address the issue of mold-contaminated housing and its impact on health. This network enabled us to set up a campaign to take air samples in mold-contaminated housing, which formed the basis for the microbiological and toxicological characterization of the bioaerosols and fungal isolates collected. A database of "degraded habitats" has thus been created and continues to be expanded, enabling statistical studies to be carried out with the specific aim of linking residents' symptoms with data from mycological and toxicological analyses. This database also enables the study of fungal species collected in indoor environments (particularlyAspergillus from the Versicolores section) that have carcinogenic properties.

Partnerships

At regional level
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  • Cancéropôle Nord-Ouest,
  • SéSAD axis of the COMUE Normandie-Université (LMSM, U2RM, PBS-BRICS laboratories of the Universities of Caen and Rouen),
  • CETAPS laboratory (University of Rouen),
  • Dermatology Department, Microbiology and Pharmacy Laboratory, Caen University Hospital,
  • Department of Occupational Medicine, Rouen University Hospital,
  • SFR ICORE.
At national level
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  • Medical physics department of the Orsay Proton Therapy Center,
  • RadeXP platform (Institut Curie, Centre de Protonthérapie, Orsay),
  • INSERM U1196/UMR9187 CMIB unit (Institut Curie- Orsay),
  • LCIB (UMR E3 CEA-UJF, Grenoble),
  • IRSET (INSERM 1085, Rennes),
  • LECA UMR 5553 (Grenoble),
  • UCEIV EA4492 (Université du Littoral Côte d'Opale, Dunkerque),
  • GRITA EA7365 (University of Lille),
  • CSTB,
  • ANSES.
At international level
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  • Liège University Hospital,
  • KNUCA University, Kiev,
  • Lebanese University (Beirut),
  • Royal Institute of Traditional Medicine of Cambodia.
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