Chemicals which induce numerical chromosome changes i.e. aneugens, may represent significant environmental hazards, as such changes in somatic cells contribute to tumour progression and in germ cells to birth defects. In the case of the induction of point mutations and chromosome structural rearrangements by chemicals, such as pesticides, the major target of chemical interactions has been clearly characterised as being the DNA of the chromosomes. In contrast, chemicals which induce numerical chromosome changes, such as polyploidy and aneuploidy, may potentially interact with a diverse range of cellular targets including all the components of the mitotic and meiotic cell cycles and their associated checkpoints. Studies (including some with EU support) have demonstrated that aneuploidy is induced by a wide range of environmental chemicals.
Currently, there are no defined and validated test systems and strategies for the detection and evaluation of chemicals which induce aneuploidy and this deficiency has been highlighted by the International Conference on the Harmonisation of Pharmaceutical Safety Evaluation (ICH 1995) and a variety of international and national regulatory and advisory bodies to the chemical industries. The aims of the project are to complete the development of a package of methods for the detection of chemical aneugens and to determine significance of exposure to chemical aneugens of germ cells of both rodents and humans.
In the proposed project the collaboratories will:
1) Determine the significance of chemical damage to components of the cell cycle.
2) Develop and validate an in vitro methodology for the detection and evaluation of aneugenic chemicals.
3) Develop and evaluate a methodology for identifying aneugenic activity in the GI tract and compare with the bone marrow.
4) Develop and evaluate methods for evaluating aneugenic potential of pharmaceuticals in male and female germ cells.
5) Provide an integrated package of methods for detecting and evaluating aneugenic environmental chemicals.
6) Evaluate the effect of acute exposures to chemical aneugens.
The project involves the collaboration between academic and chemical industry laboratories and will make a major contribution to the development of safe chemical within the European Union.
Key Words: Aneugenic chemicals, hazard evaluation, acute exposures, test development.
Funding SchemeCSC - Cost-sharing contracts