Chromatin structure and its cell cycle kinetics in intact and irradiated cell nuclei
| Authors | |
|---|---|
| Year of publication | 1999 |
| Type | Article in Proceedings |
| Conference | Fundamentals for the assesment of risks from environmental radiation |
| MU Faculty or unit | |
| Citation | |
| Field | Genetics and molecular biology |
| Description | The prototype of the genetic aberration which is found in leukemias is the t(9;22) translocation involving ABL and BCR genes typical of chronic myeloid leukemia (CML) which is frequently induced by radiation. In this study, the structural characteristics of these chromosomes and genes were investigated. We showed that both in interphase and prometaphase the average distance between ABL and BCR genes is substantially shorter than the that of randomly distributed genes. Therefore, one of the reasons of high incidence of CML may be the physical closeness of ABL and BCR genes in cell nuclei. The chromatin structure undergoes substantial changes during the cell cycle. We have found that, after the stimulation of lymphocytes, the ABL and BCR genes move towards the membrane, their mutual distances increase, and the minimum distance between heterologous ABL and BCR genes increases. From experiments in which sister cell nuclei were analysed we can conclude that the cell cycle dependent movement of individual genes is predetermined to some extent at the moment of cell division. The so called intermingling or random walk of chromatin are rather limited. The original chromatin structure and its cell cycle dependent evolution are disturbed in irradiated cells. We found that the positions of ABL and BCR genes in irradiated and stimulated lymphocytes are shifted to the centre of the nucleus, they are closer to each other and also the distances between heterologous ABL and BCR genes are shorter. Therefore, radiation increases the probability of ABL-BCR interaction during the first cell cycle after irradiation. Average values of the topological parameters of ABL and BCR genes are similar for different cell lines and different individuals. On the other hand, we found statistically significant variations in bone-marrow cells of healthy individuals (and CML patients). We suggest that individuals with shorter ABL-BCR distances are more likely to suffer from leukemia in future. |
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