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Date of Award

5-1984

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Medical Sciences (Growth and Development)

Supervisor

Irene Uchida

Abstract

There are some data from human epidemiological studies which suggest that radiation has a small but significant effect in causing aneuploid gametes. Alberman et al. (1972) suggested that much of this radiation occurred more than ten years before the conception of the abnormal child. Mice have been used to study experimentally radiation effects on chromosome segregation. Radiation induces nondisjunction in several strains, including (C₃HxICR/Swiss)F₁ females. The present study was designed to investigate the possibility of repair of the mechanisms which results in nondisjunction following irradiation.

Female (C₃HxICR/Swiss)F₁ mice were randomized into 4 experimental groups at 6-8 weeks of age. Some were irradiated at 3 months with 20 R gamma rays from a ¹³⁷Cs source. Young mice were sacrificed at 3 months of age, within 24-48 hours of irradiation. Others were irradiated then housed until 9 months old. At the time of sacrifice ovaries were removed and the oocytes obtained were cultured to the metaphase II stage. Chromosomes were then analyzed.

Oocytes from 974 mice were studied. The frequency of spontaneous nondisjunction in oocytes from young mice was quite low (0.2%) and this increased significantly after irradiation to 1.6% (p=0.001). The spontaneous frequency of nondisjunction in oocytes increased with age from 0.2% to 1. 2%. In contrast the nondisjunction frequency in oocytes from irradiated-aged animals was 0.0%. In other words, following irradiation at a young age, no aneuploid oocytes were recovered. This is significantly different from the frequency in control aged animals, p=0.002.

The mechanism by which radiation causes nondisjunction is not known. Possibilities include damage to the centromere region or radiation could act, by causing premature or accelerated terminalization of chiasma.

The disappearance of aneuploid oocytes in irradiated-aged animals in this study suggests that in addition to causing nondisjunction immediately there is a delayed effect somewhere between 48 hours and 6 months which results in an elimination of abnormal cells. This experimental finding in mice is quite different from epidemiological information from humans. It provides an avenue for further research into agents causing chromosome abnormalities and the factors involved in germ cell selection and survival.

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