Objective
Ionizing radiation is very efficient in inducing chromosomal aberrations which are associated with human hereditary effects as well as in neoplasia. This proposal is complementary to the already running project (PL950004) and designed to study factors which influence or modify the formation of radiation induced chromosomal aberrations in mammalian cells.
It focuses on intragenomic heterogeneity in radiation induced chromosome aberrations, formation of exchange aberrations and individual susceptibility in radiation response.
To understand the influence of chromatin structure on induction and repair of radiation induced damage, studies will be carried out in Chinese hamster primary cells which have distinct hetero(condensed) and eu-chromatin (open, transcriptionally more active) by using conventional Gbanding and fluorescence in situ hybridization (FISH).
In addition, in human and Chinese hamster cells special emphasis will be given to chromosomes which are extrememly rich in actively transcribed genes and those with limited transcriptional activity by using chromosome specific DNA libraries.
The kinetic of formation of exchange aberrations (unstable, dicentrics; and stable, translocations) in human lymphocytes following treament with ionizing radiation at different stages of cell cycle (Go and G2), different dose levels as well different recovery periods will be investigated using premature chromosome condensation and FISH techniques.
The defects underlying radiosensitivity of cell are variable in many cases and poorly defined.
For chemicals, involvement of several genes (i.e. glutathione transferase) in modifying biological responses have been demonstrated.
Influence of defects in glutathione transferase and N-acetyltransferase genes on sensitivity to ionizing radiation will be studied using different cohorts. The results obtained from this project will give new insights on different aspects of the role of chromatin structure, mechanisms of radiation induced chromosome aberrations and the factors that contribute to the observed yield of aberrations.
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Programme(s)
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Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
2300 RA Leiden
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.