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Contenido archivado el 2024-04-15

EXPERIMENTAL STUDIES OF THE MECHANISMS OF SPONTANEOUS AND RADIATION-INDUCED NON-DISJUNCTION IN THE FEMALE MOUSE

Objetivo


The incidence of chromosome anomalies induced by irradiation of mouse oocytes at various stages of preimplantation and postimplantation embryonic development were compared.
ANEUPLOIDY PRESENTS A SERIOUS GENETIC HAZARD TO THE HUMAN POPULATION. NUMERICAL CHROMOSOME ANOMALIES ARE PRESENT IN UP TO 50% OF SPONTANEOUS ABORTUSES. MOREOVER, ALMOST ONE-HALF OF NEW BORN CHILDREN WHO HAVE CHROMOSOME ANOMALIES ARE SIMILARLY ANEUPLOID.
GIVEN THE HIGH LEVELS OF SPONTANEOUSLY OCCURING ANEUPLOIDY IN THE HUMAN POPULATION, IT IS NOT SURPRISING THAT A LARGE NUMBER OF RETROSPECTIVE AND PROSPECTIVE EPIDEMIOLOGICAL STUDIES HAVE BEEN CARRIED OUT TO IDENTIFY FACTORS WHICH MAY INFLUENCE THE LEVEL OF ANEUPLOID CONCEPTIONS. TO DATE, ONLY MATERIAL AGE HAS BEEN SHOWN UNEQUIVOCALLY TO AFFECT THE INCIDENCE OF ANEUPLOIDY. HOWEVER, EXPOSURE TO ENVIRONMENTAL MUTAGENS, SUCH AS RADIATION, HAS ALSO BEEN SUGGESTED TO BE OF IMPORTANCE. MANY EXPERIMENTAL STUDIES, USING THE MOUSE AS THE TEST ORGANISM, HAVE THEREFORE BEEN INITIATED TO EXAMINE THE POTENTIAL OF VARIOUS AGENTS TO INDUCE CHROMOSOME NON-DISJUNCTION.
RECENT RESULTS FROM THIS LABORATORY HAVE SHOWN THAT X-RAYS ARE ABLE TO INDUCE MEIOTIC CHROMOSOME NON-DISJUNCTION IN FEMALE MICE. A LINEAR DOSE-RELATED RESPONSE WAS FOUND FOLLOWING EXPOSURE OF IMMEDIATELY PRE-OVULATORY OOCYTES TO COMPARATIVELY LOW DOSES OF X-RAYS, WHILE A LINEAR-QUADRATIC DOSE-RELATED RESPONSE WAS PRESENT SFTER LARGER X-RAY DOSE TREATMENTS OF DICTYATE OOCYTE STAGES.
ALTHOUGH THESE STUDIES HAVE SHOWN THAT X-IRRADIATION CAN INDEED INDUCE NON-DISJUNCTION IN MOUSE OOCYTES, THE MECHANISMS OF INDUCTION REMAIN INCERTAIN. IT IS NOW CLEAR, FOR EXAMPLE, WHETHER THE TRISOMIC EMBRYOS OBSERVED IN THESE EXPERIMENTS WERE PRIMARY OR TERTIARY IN CHARACTER. IF THE FORMER, THEN X-RAYS ARE ABLE TO INDUCE NON-DISJUNCTION IN STRUCTURALLY NORMAL CHROMOSOMES. HOWEVER, IF THEY ARE OF THE LATTER TYPE, THE NON-DISJUNCTIION INDUCING PROPERTY OF X-RAYS IS ASSOCIATED WITH THE ABILITY TO INDUCE CHROMOSOME STRUCTURAL REARRANGEMENTS.
IT IS PROPOSED TO EXAMINE THIS QUESTION MORE THOROUGHLY BY DETAILED KARYOTYPIC ANALYSIS OF POST-IMPLANTATION MOUSE EMBRYOS IN UNIRRADIATED FEMALE MICE AND IN FEMALES GIVEN AN X-RAY TREATMENT KNOWN TO INDUCE A SIGNIFICANT INCIDENCE OF NON-DISJUNCTION. THIS APPROACH SHOUL PROVIDE INFORMATION ON:
1) SPECIFIC CHROMOSOMES INVOLVED IN SPONTANEOUS NON-DISJUNCTION;

2) SPECIFIC CHROMOSOMES INVOLVED IN RADIATION-INDUCED NON-DISJUNCTION;

3) THE RELATIVE PROPORTIONS OF PRIMARY AND TERTIARY TRISOMIC EMBRYOS. THIS LATTER POINT SHOULD PERMIT A BETTER UNDERSTANDING OF THE MECHANISMS OF RADIATION-INDUCED NON-DISJUNCTION.

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Medical Research Council (MRC)
Aportación de la UE
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20 Park Crescent
W1N 4AL London
Reino Unido

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