Objective
EVALUATION OF NON-STOCHASTIC RISKS TO THE DEVELOPING ORGANISM. DAMAGE TO THE BRAIN AFTER PRENATAL IRRADIATION.
In the present experiments the deoxyribonucleic acid (DNA) repair capability of the foetal brain and liver has been analysed simultaneously with long term observations of rats which were treated in utero either by X-irradiation, ethylnitroso urea (ENU) or both in combination. This should reveal any relationship between the influence on O6-alkylguanine-DNA alkyltransferase activity, which is the specific acceptor protein in the DNA repair process, and the incidence of tumours in the offspring.
X-IRRADIATION (180 KV, 0.2 MM CU, 0.01 GY/MIN; DOSES: 0.25 GY, 0.50 GY, 1.00 GY, AND 1.50 GY) WILL BE APPLIED TO PREGNANT RATS IN THE MORNING OF DAY 14 OF GESTATION. ETHYLNITROSOUREA (ENU) (30 MG/KG BODY WEIGHT) ALONE OR SUBSEQUENT TO X-IRRADIATION WILL BE APPLIED AT THE END OF DAY 14 (INTERVAL 8-12 HOURS). THIS DEVELOPMENTAL STAGE HAS BEEN CHOSEN BECAUSE BOTH ENU AND X-IRRADIATION STILL EXERT A MARKED TERATOGENIC POTENCY WHEREAS THE NEUROONCOGENIC POTENCY OF ENU IS ALREADY INCREASING.THE OFFSPRING FROM THE TREATED ANIMALS, AS WELL AS FROM THE UNTREATED CONTROLS WILL BE REARED BEYOND WEANING.INVESTIGATIONS WILL BE PERFORMED AT THE FOLLOWING TIMES:A.-ON DAY 19 OF PREGNANCY, TO CHARACTERIZE THE HISTOGENETIC EFFECTS AT THE FOREBRAIN IMMEDIATELY BEFORE BIRTH.B.-AT 3-4 MONTHS, IN ORDER TO COMPARE THE OCCURENCE OF RESIDUES OF THE PRENATALLY INDUCED ROSETTES WITH THE ORIGIN, TYPE AND LOCATION OF NOW ARISING EARLY NEOPLASTIC LESIONS.C.-AT 12-16 MONTHS, RESIDUAL DYSPLASTIC LESIONS ARE CORRELATED WITH OVERT GLIOMA FORMATION. ONLY THE LATTER TYPE OF TUMOR CAN YIELD RELIABLE DATA BECAUSE IT REPRESENTS ABOUT 85% OF ENU-INDUCED BRAIN TUMORS.MEMBRANE PROPERTIES OF HETEROTOPIC CELLS REPRESENT AN ALTERNATIVE PATHWAY IN RADIATION TERATOLOGY, COMPLEMENTARY TO DNA-RELATED RESEARCH.IT IS SURMISED THAT THE CORRELATIONS EXIST BETWEEN THE OUTSTANDING ADHESIVE PROPERTIES OF THE HETEROTOPICALLY DISPLACED CELLS AND THEIR NEGATIVE INFLUENCE UPON CARCINOGENESIS. THIS IMPLIES STUDIES OF EMBRYONIC AND TUMOR SPECIFIC ANTIGENS AND THEIR POSSIBLE CROSS-REACTIVITIES. CHARACTERIZATION OF THE SURFACE PROPERTIES OF CNS CELLS CONTRIBUTING TO THE NORMAL MICROSCOPIC ANATOMY AS WELL AS OF CELLS LOCATED WITHIN LESIONS. CHARACTERIZATION OF THE LECTIN BINDING PROPERTIES, USING PNA, WGA, SBA, RCA WHICH ARE SPECIFIC FOR DEVELOPING NEUROECTODERMAL TISSUES, BUT ALSO FOR CERTAIN BRAIN TUMORS.CHARACTERIZATION OF CELL ADHESION-RELATED ANTIGENS BY MEANS OF SPECIFIC ANTIBODIES. TOPOGRAPHICAL DISTRIBUTION PATTERN OF PEROXIDASE-LABELLED OR OF FITC-LABELLED ANTIBODIES IN NORMAL AND IN PATHOLOGICALLY ALTERED BRAIN TISSUE. CORRELATION BETWEEN THE ANTIBODY AFFINITY PATTERN AND THE DEGREE OF MALFORMATION OR THE TYPE AND ORIGIN OF GLIOMAS.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine obstetrics
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Coordinator
85764 NEUHERBERG
Germany
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