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Method normalisation, validation protocols and quality control for biomonitoring tests for mutagens/carcinogens

Research project NM/A/20 (Research action NM)

Persons :

Description :

CONTEXT

The project is situated in the context of the development of suitable biomonitoring tests for carcinogenic substances. It is believed that controlling environmental exposures to carcinogens might prevent most of the cancers. To achieve this, reliable biomonitoring tests are essential. These will help to better understand the mechanisms responsible for cancer induction, to classify the environmental carcinogens and finally, on the basis of these data, to allow pertinent prevention.


THE PROJECT

The general goals of this proposal with respect to specific biomonitoring assays (described below) for carcinogens are:
- to perform a method validation;
- to establish standard operating procedures for each method in accordance with the validation protocol. These procedures should be suitable for incorporation into a normalised method;
- to devise procedures for quality assurance.


THE PARTNERS

The "Rijksuniversiteit Gent - Laboratorium voor Standaarddosimetrie" is working on the micronucleus test. The micronucleus (MN) assay is a valuable tool for the assessment of chromosomal damage induced by ionising radiation or chemicals. Compared to other cytogenetic methods the scoring in the MN assay is relatively fast allowing monitoring of genotoxic effects in large populations.

The "Vrije Universiteit Brussel - Laboratorium voor Cellulaire Genetica" contributes to the further development of the comet assay. This assay allows the detection of DNA damage at the single cell level. It is a useful assay to identify cancer hazards, more specifically by demonstrating recent attack of genotoxicants on DNA. The research team is also working on a micronucleus assay.

The "Université Catholique de Louvain - Unité de Toxicologie Industrielle et Médecine du Travail", is doing work on analytical methods to measure arsenic compounds in human urine. These methods involve the identification of various arsenic compounds originating from the consumption of sea food, as well as the major metabolites of inorganic arsenic compounds originating from environmental exposures.

The "Katholieke Universiteit van Leuven - Laboratorium voor Arbeidshygiëne en Toxicologie" is involved in the development of a sensitive method to measure haemoglobin adducts. These adducts are comparable to the reaction products, which carcinogenic substances may form when they come into contact with DNA. Such reaction products can be viewed as a primary cause of the damage to DNA. The test is developed for haemoglobin instead of DNA because the latter is far more difficult to obtain in sufficient quantities from human blood.


EXPECTED PRODUCTS AND RESULTS

The availability of better validated biomonitoring tests can contribute in several ways to the advancement of cancer epidemiology. It is expected that these markers will not only allow the early identification of potential risks to humans, but will also provide comparative dosimeter and response data, which will greatly benefit cancer research.

Alongside the benefits for epidemiological research, improved methods in biomonitoring will also result in a better risk surveillance and risk control.

- With respect to the first, the means available to occupational and community medicine to monitor exposure and effects of carcinogens are at present very limited. More specific and sensitive methods will aid immensely to target populations who are at special risk.

- One aspect of cancer prevention is the control of risks through regulatory measures, which have to be implemented by the responsible governmental bodies, both on national and supranational levels. The importance of reliable biomonitoring tests in the latter context not only resides in the fact that these tests may be instrumental in proving cancer risks, but that they may also form the basis for establishing limit values for acceptable exposure to control these risks.


USERS COMMITTEE

- V. Merken (Ministry of Economic Affairs, Belgian Organisation for Accreditation and Conformity Assessment)
- R. Grosjean (Ministry of Labour, Laboratory for Industrial Toxicology)
- H. Janssens (Belgian Institute for Standardisation)
- M. Van Hoorne (Vlaams Wetenschappelijke Vereniging voor Arbeidsgezonheidskunde)
- C. de Brouwer (Société Belge de Médecine et d’Hygiène du Travail)
- N. Van Nimmen (Belgian Society for Occupational Hygiene)


PROMOTERS

Hendrik VEULEMANS
Katholieke Universiteit Leuven
Laboratorium voor Arbeidshygiëne en Toxicologie
Kapucijnenvoer 35/5
B-3000 LEUVEN
Tel: +32 16 33.70.80
Fax: +32 16 33.69.97
E-mail: hendrik.veulemans@med.kuleuven.ac.be

Micheline KIRSCH-VOLDERS
Vrije Universiteit Brussel
Laboratorium voor Cellulaire Genetica
Pleinlaan 2
B-1050 BRUSSEL
Tel: +32 2 629.34.23
Fax: +32 2 629.27.59
E-mail: mkirsch@vub.ac.be

Jean-Pierre BUCHET
Université Catholique de Louvain
Unité de Toxicologie industrielle et environnementale
Clos Chapelle-aux-Champs 30, bte 30 54
B-1200 BRUXELLES
Tel: +32 2 764.32.22
Fax: +32 2 764.32.28
E-mail: buchet@toxi.ucl.ac.be

Hubert THIERENS
Rijksuniversiteit Gent
Faculteit Geneeskunde
Vakgroep Biomedische Fysica & Radioprotectie
Proeftuinstraat 86
B-9000 GENT
Tel: +32 9 264.66.43
Fax: +32 9 264.66.99
E-mail: hubert.thierens@rug.ac.be

Documentation :

Method normalisation, validation protocols and quality control for biomonitoring tests for mutagens/carcinogens : final report    Brussels : Federal Science Policy, 2005 (SP1478)
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