Objective
Achievements have been made in the following areas:
Relationship between initial damage and the yield of aberrations
Factors responsible for increased sensitivity in radio-sensitive cell lines
Relationship between the yields of stable and unstable aberrations and their elimination during proliferation
Chromatin structure in relation to induction and distribution of radiation induced aberrations
Role of modifiers on the yield of radiation induced chromosomal aberrations
Studies on low dose effects and adaptive response
Training of scientists from East European countries (PECO project).
In addition to classical chromosome analysis, techniques of premature chromosome condensation (PCC), poration of cells with streptolycin-O, fluorescent in situ hybridization (FISH) using chromosome specific DNA libraries as well as region specific DNA probes have been employed in the project. Under the PECO project, Bulgarian scientists were trained in some of these techniques.
Basic mechanisms involved in the formation of radiation induced chromosomal aberrations in human lymphocytes/fibroblasts will be investigated using cytological and biochemical techniques. The relation between DNA repair and formation of aberrations will be studied by the technique of premature chromosome condensation (PCC), by fusing irradiated lymphocytes with mitotic CHO cells at different times following irradiation with neutron irradiation. Interaction experiments with short wave UV and X-rays will be carried out to clarify the mechanism underlying the synergistic effects for induction of chromosome aberrations observed in such combinations, in an attempt to discriminate between different possible mechanisms i.e. interaction between lesions or changes in the chromatin structure. The basis for the increased chromosomal sensitivity to radiation following hyperthermia will be studied using PCC technique. By the method of Streptolicin O-poration, different nuclear protein fractions or repair enzymes will be introduced into different types of radiosensitive CHO mutant cells (deficient or proficient in DNA double strand break repair) to explore the possibility of correcting and identifying biochemical defects in these cell lines. The frequencies of stable chromosome aberrations (translocations) induced by different types of radiation, dose rates and dose fractionation regimes will be studied by painting the chromosomes by specific DNA libraries and in situ hybridization. with this sensitive technique it has been shown that translocations are induced at a higher frequency than dicentrics following X-irradiation. Inter
individual variation to radiation response will be studied following G2 irradiation and PCC or conventional chromosome aberration analysis. In this study breast cancer patients who do or do not respond to radiotherapy will also be included. The problem of low dose/dose rate effects for induction of aberrations will be studied by 'adaptive response' type of experiments, in which the lymphocytes are adapted with very low dose of radiation and challenged later with a higher dose. Specific protein inhibitors will be used at different times during the adaptive condition to detect the duration of induced state of the cells. In addition, lymphocytes of Uranium miners will be used to check whether adaptation occurs in vivo as well.
Fields of science
Programme(s)
Topic(s)
Data not availableCall for proposal
Data not availableFunding Scheme
CSC - Cost-sharing contractsCoordinator
2300 RA Leiden
Netherlands