NEWS

PRESS RELEASE – DECEMBER 2^nd, 2014

The ComPack project is a French-Norwegian¹ collaborative research and innovation project that addresses the need for reliable and validated testing for industry and academia to assess the effect of chemicals on human health and the environment. The public-private consortium plans to develop by the end of 2016 a high throughput, automated, versatile, validated and user-friendly DNA testing facility based on the innovative modified comet assay.
The comet assay is the most widely used method for measuring DNA damage in eukaryotic cells. This test system is used for environmental agents as well as in human biomonitoring, for endogenous damage and antioxidant resistance analysis and DNA repair. The comet assay is employed by the pharmaceutical, cosmetic and chemical industries for screening novel drugs and chemicals for genotoxicity. The genotoxicity testing market is rapidly growing and is expected to reach €3,210 million in 2018², 50% of which is currently represented by the cosmetics and personal-care industry and 32% by the pharmaceutical segment.

Standard procedures for genotoxicity testing have been laid down by, among other organisations, the European Food Safety Authority (EFSA) and the International Committee for Harmonisation (ICH).
OECD guidelines are in preparation for the comet assay in in vivo genotoxicity testing, with the advantage that it can be applied to virtually all tissues. JACVAM (Japanese Committee for the Validation of Alternative Methods), in association with the corresponding European committee, ECVAM, is carrying out validation trials for the in vitro assay. REACH regulations (Registration, Evaluation, Authorisation and Restriction of Chemical substances) stipulate that chemicals whose usage per annum exceeds a certain level must be registered with details of toxicity for humans and possible environmental impact. As such, the comet assay is mentioned by REACH as a suitable assay for in vitro tests.

A new plant-based comet assay to complement and strengthen conventional techniques
The comet assay is also a potentially powerful ecological research tool for assessing DNA damage and repair in sentinel animals such as mussels, eathworms or mice and plants in the environment. However, despite their fundamental roles in every ecosystem, plants have not been much used in these studies. There is therefore a need to develop an alternative, fast, cost-efficient, reliable and more informative plant-based assay. The project aims to increase several-fold the capacity and versatility of the comet assay, by adapting high troughput approaches for different cell types and for plants, incorporating enzymes with a range of lesion specificities.

The Human Hepatic cell line HepaRG™ used for the new comet assay
Many chemicals are genotoxic only after activation. HepaRG™ is a well-known human hepatic cell line commercially available through Biopredic International, which, unusually, can differentiate into fully functional hepatocytes. These are particularly useful in genotoxicity testing, as they retain xenobiotic metabolizing (phase I and phase II) enzymes and so can activate many potential carcinogens, unlike most permanent cell lines. Adapting the cells for use in the new comet assay will require the advanced cell culture skills of the French CRO Eurosafe, together with comet assay experience.

All partners part of the project have proven expertise in relevant technological development to cover together the whole range of project needs. Overall, the Compack project will help chemical, nanomaterials, cosmetic, pharmaceutical and food industries and CROs by delivering them all components for a more versatile, high throughput and fully automated comet assay for better safety of all chemicals, drugs, cosmetics and foods exposure of human and the environment.

ABOUT

NorGenoTech AS (NGT) was founded as a direct consequence of the success of the ‘COMICS’ project. The core facilities of the company are based at the Department of Nutrition, Oslo University, which provides a productive research environment and modern laboratory facilities. The founders of NGT have extensive experience in running and participating in national and EU projects: most recently, COMICS and NewGeneris (FOOD-CT-2005-016320). The company has carried out R&D for industrial and academic customers, e.g. Kraft Foods Europe, Statoil, Elchrom Scientific, and Norwegian Institutes for Air Research and Water Research.

University of Oslo. Andrew Collins' group is responsible for various comet assay innovations, most recently through the EC-funded STREP, COMICS (LSHB-CT-2006-037575). Collaboration with Magnar Bjårøs (University of Oslo) is essential for adapting novel enzymes.

LGCgE (Equipe Sols et Environnement – Laboratoire Génie Civil et géo Environnement) is a French semi-public laboratory working for more than 30 years on soil contamination and the impacts of pollutants on human health and environment. It has developed several plant biomarkers to assess toxic effect of pollutants on the environment. LGCgE aims at advising national and local authorities on the management of polluted sites and pollution management. www.lgcge.fr

Xenoblis, now part of Eurosafe, was created more than 25 years ago by experts in hepatocyte isolation, Professors André Guillouzo and Christiane Guguen-Guillouzo, INSERM researchers. It has recently joined the French CRO EUROSAFE. Research on the liver remains the main focus in Eurosafe’s vitro team. The HepaRG® cell line, sold by Eurosafe sister company Biopredic International (supplier of biologicals for Research), provides a new tool based on inducible hepatocyte differentiation. Learn more on www.heparg.com

IMSTARS.A., a private SME company founded by Dr Françoise Soussaline, focuses on developing innovative instruments for automated biomedical imaging and high throughput analysis in genetic toxicology, cytogenetics and cytopathology. Based on the Pathfinder™ range of High-Content Image Analysis systems, IMSTAR has patented an extensive set of technologies including software, hardware and content. The company was also a partner in the EU project COMICS. www.imstarsa.com 

Scientific contact:
Dr Sergey Shaposhnikov - sas[at]norgenotech.no

Press Relations:
Heidi Vincent – Marketing & Communications Manager - Contact

¹ The public/ private ComPack consortium includes 5 organisations:

- The project initiator, NorGenoTech AS (NGT) lead by Pr. Andrew Collins, Dr Gunnar Brunborg and Dr Sergey Shaposhnikov which facilities are based at the Department of Nutrition, Oslo University
- The Department of Nutrition, part of the Medical Faculty of the University of Oslo
- LGCgE – Equipe Sols et Environnement – Laboratoire Génie Civil et géo Environnement
- Eurosafe, a CRO based in France, Britanny (that has recently acquired Xenoblis)
- IMSTAR SA, a French private SME 

² According to Transparency Market Research.

Download the press release >>

Figure 96-gel-high-throughput-format

The comet assay is a sensitive and versatile method for detecting DNA damage in eukaryotic cells. Alkaline electrophoresis of agarose-embedded, lysed cells (nucleoids) produces comet-like images, with broken DNA loops comprising the tail; the relative intensity of the tail indicates the frequency of DNA breaks.

Read the full press release (pdf) in English

About Biopredic International
Since 1993, Biopredic International produces and distributes human and animal products (tissues, primary cells, cell lines, blood products, fluids) for academic and industrial research in drug discovery, drug development and cosmetics. Biopredic International is recognized worldwide for its expertise in liver products (tissues, primary cells) and is the exclusive worldwide licensor of the HepaRG™ cell line.
Visit www.heparg.com

About InvitroCue
InvitroCue provides innovative products and services in the fields of in vitro DMPK, in vitro toxicology and digital pathology utilizing cell-based models and image analysis tools. InvitroCue's technologies and assays have been developed and validated together with renowned leading pharmaceutical companies and scientific collaborators, such as the Agency for Science, Technology and Research (A*STAR), National University of Singapore (NUS), Massachusetts Institute of Technology (MIT) and renowned pathologists. The company currently owns several 3D in vitro cell culture models for long term hepatocyte culture and various image analysis tools for automated quantification of cells and tissue. InvitroCue uses these technologies and assays to support better decision making in preclinical studies, clinical trials and diagnostics. Its solutions can be applied in the realms of drug testing as well as research and development of cosmeceuticals and medical devices. InvitroCue was established in 2012 as a spin-off from A*STAR and is headquartered in Singapore.

Real time in vitro evaluation of the carcinogenic potential of contaminants

The Genotrace project, combining targeted research and technology transfer¹, aims at delivering an innovative test to improve the safety of chemical products, drugs, human and animal food and the environment. The project consortium is led by INRA (French National Institute for Agricultural Research) and includes CNRS (French National Center for Scientific Research), the University Toulouse III – Paul Sabatier and the company Biopredic International. 
The Genotrace project has just received the support of the French National Research Agency (ANR) for three years. 

Among the current short-term assays developed to assess DNA damage induced by a physical or chemical agent, the micronucleus assay (MN) represents a reliable and precise method that is already validated as a regulatory test in a battery of predictive tests for carcinogenesis. The Genotrace project aims at bringing major technological innovations to develop a new MN assay, that will allow to monitor both dynamically and in real time the production of chromosome damages and the signal of a genotoxic reporter on HepaRG^® cells (HepaRG^® cells can metabolize chemical compounds, this metabolization step is required for many carcinogenic compounds).

A new test for real time monitoring

The new test developed within the Genotrace project will rely on fluorescent biotracers recently generated by the academic partners (INRA, CNRS, University Toulouse III - Paul Sabatier). The first biotracer will allow visualizing the chromatin (the DNA filament associated to proteins, forming the chromosomes), without cellular toxic effect, thus allowing the dynamic monitoring of the cellular chromatin in real time. Second, the expression of a specific gene will allow the evaluation of any associated activation of the DNA damage pathway. Therefore the test will provide information on the micronuclei origin, whether induced by mechanisms of DNA breaks (clastogenic) or produced through the abnormal chromosomes distribution during mitosis (aneugenic). To take into account the metabolism of many chemical compounds, these biotracers will be stably expressed in the HepaRG® cells, human liver cells that are metabolically active, optimized for the MN test by BIOPREDIC International.

The developed in vitro MN assay will be adapted to a medium- to high throughput straightforward readable assay, thanks to the implementation of high content screening imaging protocols and the development of an image analysis and classification-based pipeline. The assay will bring new capacities to the classic MN assay and may lead to breakthroughs in the prevention and/or the diagnosis of exposure to genotoxicants present in the environment, food or future drug candidates.

The innovative genotoxicity test developed by the Genotrace stakeholders will be able to answer today’s recommendations, with significant improvements in the scientific, technical and economical fields. Overall, the Genotrace project aims to a better safety of all chemicals, drugs, and foods exposure of human, farm animals/pets and environment.

Read the full press release (pdf) in English or in French.

What is the micronucleus assay?
As the name suggests, the MN test is based on the presence of DNA breaks visible as small pieces after coloring. Two mechanisms contribute to the formation of micronuclei: a break of chromosome or a defect in the chromosome distribution, at the end of the cell division stage. This test is performed either on cells, generally lymphocytes from an animal or a human exposed to genotoxic products or on cells cultured in vitro. Whilst the assessment of disruptions in vivo cannot be foreseen, the MN test, in its in vitro version, does not enable a real time evaluation of the disruptions that will lead to the formation of micronuclei, and thus prevents the identification of the mechanism causing the chromosome fragments.

^{...............................................................................................................................................
1} The public/ private Genotrace consortium includes the project initiator, INRA joint research unit « Food Toxicology » (Toxalim) , the “Institut des technologies avancées en sciences du Vivant” (ITAV) of the CNRS and  Toulouse III - Paul Sabatier university, and the company Biopredic International, that markets the human hepatic cell line HepaRG^®. 

Scientific contact
Bernard Salles, Toxalim unit, INRA Toulouse, France
bernard.salles[at]toulouse.inra.fr or 00 33 5 61 28 51 41

Press contact
Biopredic International – Dr. Christophe Chesné - christophe.chesne[at]biopredic.com. GSM: 00 33 (0)6 21 10 75 18