Formation Of Aneuploid Cells Research Articles

Centrosomes split in the presence of impaired DNA integrity during mitosis.

A well-established function of centrosomes is their role in accomplishing a successful mitosis that gives rise to a pair of identical daughter cells. We recently showed that DNA replication defects and DNA damage in Drosophila embryos trigger centrosomal changes, but it remained unclear whether comparable centrosomal responses can be provoked in somatic mammalian cells. To investigate the centrosomal organization in the presence of impaired DNA integrity, live and ultrastructural analysis was performed on gamma-tubulin-GFP and EGFP-alpha-tubulin-expressing Chinese hamster ovary cells. We have shown that during mitosis in the presence of incompletely replicated or damaged DNA, centrosomes split into fractions containing only one centriole. This results in the formation of multipolar spindles with extra centrosome-like structures. Despite the extra centrosomes and the multipolarity of the spindles, cells do exit from mitosis, resulting in severe division errors. Our data provide evidence of a novel mechanism showing how numerous centrosomes and spindle defects can arise and how this can lead to the formation of aneuploid cells.

Use of mesothelial cell cultures to assess the carcinogenic potency of mineral or man made fibers

Natural mineral fibers may produce pulmonary cancers and mesothelioma. In contrast with lung cancer, the incidence of fiber-induced mesothelioma is not enhanced in smokers compared to non smokers. It is therefore of special interest to use mesothelial cells to study the toxicity of natural or man made mineral fibers. Several years ago, we have developed a method to culture rat pleural mesothelial cells (RPMC). We have first studied the effects of asbestos fibers by the application of in vitro tests formerly developed to determine the genotoxicity and transforming potency of soluble xenobiotics. Moreover, we have determined whether RPMC expressed cytochromes P450 known to metabolize polycyclic aromatic hydrocarbons. This paper reviews the results obtained so far. It has been found that asbestos fibers produced a cell transformation and a genotoxicity characterized by the formation of aneuploid cells, abnormal anaphases, chromosomal aberrations and DNA repair (UDS). In addition, RPMC expressed different forms of cytochromes P450. It is nowadays suggested that the tumorigenic potency of asbestos fibers may be related to the fiber dimensions, to their surface properties and in vivo biopersistence; this term involves the fiber solubility in biological medium and the fiber epuration from the lung by clearance mechanisms. Experiments are now in progress to determine whether the in vitro effects are dependent on the fiber parameters suggested as playing a role in the carcinogenic potency.

Double Trisomy as a Mosaic. Case History (48,XYY,+21/47,XY,+21) and Survey of the Literature of Mixed Autosomal-Gonosomal Trisomies

The case of a boy is reported showing the typical symptoms of Down's syndrome, in whom the chromosome analysis revealed a mosaic karyotype: 50% 48,XYY,+21/50% 47,XY,+21. Findings of 92 cases from the literature are summarized to show the frequencies of double gonosome-autosome aneuploidies compared with single trisomies. Referring to the different chromosomes involved, the aneuploid cell formation, the frequencies of combinations, as well as the tendency to mosaic formation are analyzed. The age of parents at the time of birth and the life expectancy are described as well as the clinical symptoms. Theories concerning the origin of double aneuploidies are discussed.

Studies on Spontaneous and Induced Mutations

1. In spite of the many and varied reports on spontaneous mutations the factors responsible for their widespread occurrence in nature have not so far been clearly understood. Investigations carried out in the present study showed that decaying organic substances like compost, cowdung and oil cakes when present in high concentrations in the soil are capable of inducing mutations of different magnitudes. Chromosome changes induced by these substances and their possible role in the production of mutations in nature are discussed in this paper.2. High concentrations of compost, cowdung and oil cake in sand exert a distinctly harmful effect as regards germination and growth. Very high concentrations of bassia oil cake (1 oil cake: 5 sand) inhibited germination. Though germination was observed in fresh cowdung the plants did not survive. No such inhibition in germination was observed in compost unmixed with sand. Lower concentrations of these substances have been found to be beneficial.3. Cytological changes induced by compost, cowdung and oil cakes were almost similar. Breakage of chromosomes followed by reunion resutling in repatterning of chromosomes (translocation and inversion), chromosome doubling leading to polyploidy and spindle abnormalities resulting in the formation of aneuploid cells were commonly observed. Chromosome clumping, cytomixis, asynapsis, erosion of chromosomes etc. were some of the other abnormalities observed.4. Quantitative analysis of the data showing the frequencies of the different abnormalities in the different treatments showed that the frequency of abnormalities increases with an increase in the concentration of the substances in the sand.5. There is a gradual decrease in the percentage of aberrations with longer duration in compost, this relation being found in the pollen mother cells also. It is suggested that this decrease may possibly be due to the gradual fall in the content of nitrogen or other substances in compost causing these aberrations.6. Cytological changes induced by a few fertilizers like ammonium sulphate, ammonium nitrate, ammonium phosphate and potassium chloride were studied with a view to comparing their effects with those of the organic manures used for the study. Abnormalities in cell division induced in the root tip cells of onion following treatment with these chemical fertilizers were almost similar to these observed in treatments with organic manures like compost, cowdung and oil cakes. The results of the studies appear to show that nitrogen, phosphorus and potassium can act as mutagenic factors in compost. The differences exhibited by compost, bassia oil cake and cowdung might probably be due to the variation in the relative concentrations of nitrogen, phosphorus and potassium present in them.7. There is striking similarity between the aberrations induced by decaying organic substances like compost, cowdung and oil cakes and those reported as occurring spontaneously. It is suggested that decaying organic matter which is present in plant environment under natural conditions in varying concentrations, and those added as manures in agricultural practices, are responsible for some at least of such spontaneous mutations which play an important part in the evolution of species.