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Chemically induced aneuploidy

Objective

Numerical chromosome changes or aneuploidy make substantial contributions to human health. The objective of the project is to provide an understanding of the mechanisms by which environmental chemicals interact with the processes of chromosome segregation at mitotic and meiotic cell division and thus produce progeny cells with abnormal chromosome numbers. An understanding of chemically induced aneuploidy will allow the development, assessment and regulation of aneugenic chemicals, the determination as to whether there is a cellular threshold for such activity and provide information on the relative activity of aneugenic chemicals in male and female germ cells.


The project activities involve research in a series of related areas :

1) Thresholds

There are theoretical reasons to assume that for at least some chemical aneugens there may be a threshold of activity. Such a threshold would allow the use of such chemicals at doses below the threshold without impairing health. Detailed dose response studies will be undertaken with selected aneugens chosen to represent different mechanisms of actions.

2) Mechanisms

Cellular targets whose modification may lead to induced aneuploidy will be investigated. These include : motor proteins, protein kinases, protein phosphotases and topoisomerases.

3) Tissue specificity and metabolism

Following the identification of the metabolic requirements for aneugenic activity in vitro, comparative studies will be performed in the tissues of rodents.

4) Comparative studies in male and female germ cells

Chemically induced aneuploidy will be analysed in both male and female germ cells with particular emphasis upon those chemicals which have produced discordant results between the two sexes.

5) Environmental significance of aneugens

Chemical aneugens for which human exposure has occurred will be evaluated in laboratory test systems.

6) System development

A major emphasis will be placed upon the application of fluorescence in situ hybridisation (FISH) techniques for the detection and assessment of chemical aneugens.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

UNIVERSITY OF WALES SWANSEA
Address
Singleton Park
SA2 8PP Swansea
United Kingdom

Participants (3)

GSF-RESEARCH CENTER FOR ENVIRONMENT AND HEALTH
Germany
Address
Ingolstaedter Landstrasse 1
85764 Neuherberg
Rijksuniversiteit Leiden
Netherlands
Address
72,Wassenaarseweg
2300 RA Leiden
Universität Bielefeld
Germany
Address
25,Universitätsstraße 25
33615 Bielefeld