Ziel
ELABORATION AND COMPARATIVE EVALUATION OF TEST SYSTEMS FOR THE ASSESSMENT OF GENETIC EFFECTS OF ENVIRONMENTAL CHEMICALS AND OF THE PRODUCTS OF THEIR METABOLIC TRANSFORMATION.
THE EXPERIMENTAL APPROACH COVERS THE DETERMINATION OF THE FREQUENCIES OF CHROMOSOMAL ABERRATIONS AND SCES INDUCED BY EPICHLOROHYDRIN, 1,2-DIBROMOETHANE, AS WELL AS THE FIVE ETHYLATING AGENTS SELECTED FOR THE EEC PROGRAMME, NAMELY ETHYL-METHANESULFONATE (EMS), N-ETHYL--N-NITROSOUREA (ENU), N-NITROSODIETHYLAMINE (DEN), DIETHYL SULFATE (DES), AND ETHYL-N-NITRO-N-NITROSOGUANIDINE (ENNG).
UNSTIMULATED LYMPHOCYTES HAVE THE CAPACITY TO REPAIR DNA LESIONS. SINCE ONE CAN CONTROL THE INITIATING CELL DIVISION IN THESE CELLS, IT IS POSSIBLE TO PERFORM LIQUID HOLDING EXPERIMENTS USING THESE CELLS.
THE INFLUENCE OF DIFFERENT DURATIONS OF LIQUID HOLDING ON THE FREQUENCIES OF CHROMOSOMAL ABERRATIONS AND SCES WILL BE DETERMINED. THE INCREASE OR DECREASE IN THE FREQUENCIES OF ABERRATIONS AS WELL AS CHANGES IN THE TYPES OF CHROMOSOMAL ABERRATIONS WILL GIVE AN INDICATION AS TO EXTENT AND TYPE OF DNA REPAIR GOING ON IN THESE CELLS.
FURTHER MORE IT IS ENVISAGED TO TREAT THESE CELLS DURING LIQUID HOLDING WITH AGENTS WHICH SPECIFICALLY INHIBIT DNA REPAIR ENZYMES SUCH AS APHIDICOLIN IN ORDER TO GET AN INSIGHT INTO THE DNA REPAIR SYSTEMS OPERTING AT THIS STAGE. IN ADDITION, EXPERIMENTS WILL BE DONE IN WHICH STIMULATED LYMPHOCYTES WILL BE HELD IN A NONDIVIDING STATE BY MEANS OF PRESTIMULATION.
IN ORDER TO COMPARE EFFECTIVELY THE RESULTS OBTAINED WITH HUMAN CELLS TO THOSE OBTAINED FROM EXPERIMENTAL ANIMALS AND SUBMAMMALIAN SYSTEMS, PARTICIPATION IN THE EEC DOSIMETRY PROJECT IS FORESEEN.