CORDIS
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Comet assay and cell array for fast and efficient genotoxicity testing

Project information

Grant agreement ID: 37575

  • Start date

    1 January 2007

  • End date

    31 December 2009

Funded under:

FP6-LIFESCIHEALTH

  • Overall budget:

    € 4 855 672

  • EU contribution

    € 3 189 385

Coordinated by:

UNIVERSITETET I OSLO

Norway

Objective

A battery of reliable and validated in vitro assays is needed to test for genotoxic and cytotoxic effects of chemicals (as in the REACH programme) without resorting to animal experiments. The comet assay, a sensitive indicator of DNA damage, will be combined in this project with the Cell Array system, to establish and validate high capacity assays suitable for chemical testing. Up to 800 cell samples will be processed for comets on a single microscope slide. Arrays will use cells with different metabolic capabilities, and data on cytotoxicity will be obtained in parallel with DNA damage. A medium-throughput assay will also be developed. Comet analysis by differential staining of damaged/undamaged DNA using established and novel dyes combined with automated image analysis will be faster and more reliable than at present.
A crucial aspect of the cellular response to DNA damage is DNA repair; variations between people can affect cancer risk. Genotoxic chemicals can act by interfering with repair.
Two methods for measuring repair, one based on the comet assay, the other using a 'Repair Chip' approach, will be compared. In addition, fluorescent probes which lock onto the DNA after hybridization ('padlock probes') will be applied to study gene-specific DNA repair. The modified comet assay methods will be assessed for reproducibility and sensitivity in an inter-laboratory prevalidation trial, using a coded set of standard chemicals, to satisfy regulatory bodies as well as industrial users of the technology. The result will be robust, validated, high-throughput in vitro genotoxicity tests. This proposal brings together academic partners and SMEs, together with a large industrial concern, and the European Centre for the Validation of Alternative Methods (ECVAM). Dissemination through professional and trade publications, regulatory channels, and scientific conferences will lead to widespread adoption of the new methods.

Coordinator

UNIVERSITETET I OSLO

Address

Problemveien 7
Oslo

Norway

Participants (14)

IMSTAR S.A.

France

JOINT RESEARCH CENTRE

Belgium

NORWEGIAN INSTITUTE OF PUBLIC HEALTH

Norway

SLOVAK MEDICAL UNIVERSITY

Slovakia

CHIRON AS

Norway

TATAA BIOCENTER AB

Sweden

ASTRAZENECA UK LIMITED

United Kingdom

THISTLE SCIENTIFIC LIMITED

United Kingdom

SEVERN BIOTECH LTD

United Kingdom

BIOPREDIC INTERNATIONAL

France

UPPSALA UNIVERSITY

Sweden

COMMISSARIAT À L' ENERGIE ATOMIQUE

France

INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE

France

USTAV EXPERIMENTALNI BOTANIKY - AKADEMIE VED CESKE REPUBLIKY

Czechia

Project information

Grant agreement ID: 37575

  • Start date

    1 January 2007

  • End date

    31 December 2009

Funded under:

FP6-LIFESCIHEALTH

  • Overall budget:

    € 4 855 672

  • EU contribution

    € 3 189 385

Coordinated by:

UNIVERSITETET I OSLO

Norway