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Distribution of ABL and BCR genes in cell nuclei of normal and irradiated
lymphocytes
S Kozubek, E Lukasova, L Ryznar, M Kozubek, A Liskova, RD Govorun, EA Krasavin and G Horneck
Institute of Biophysics, Academy of Sciences, Brno, Czech Republic.
Using dual-color fluorescence in situ hybridization (FISH) combined with
two-dimensional (2D) image analysis, the locations of ABL and BCR genes in
cell nuclei were studied. The center of nucleus-to-gene and mutual
distances of ABL and BCR genes in interphase nuclei of nonstimulated and
stimulated lymphocytes as well as in lymphocytes stimulated after
irradiation were determined. We found that, after stimulation, the ABL and
BCR genes move towards the membrane, their mutual distances increase, and
the shortest distance between heterologous ABL and BCR genes increases. The
distribution of the shortest distances between ABL and BCR genes in the G0
phase of lymphocytes corresponds to the theoretical distribution calculated
by the Monte-Carlo simulation. Interestingly, the shortest ABL-BCR
distances in G1 and S(G2) nuclei are greater in experiment as compared with
theory. This result suggests the existence of a certain regularity in the
gene arrangement in the G1 and S(G2) nuclei that keeps ABL and BCR genes at
longer than random distances. On the other hand, in about 2% to 8% of
lymphocytes, the ABL and BCR genes are very close to each other (the
distance is less than approximately 0.2 to 0.3 microm). For comparison, we
studied another pair of genes, c-MYC and IgH, that are critical for the
induction of t(8;14) translocation that occurs in the Burkitt's lymphoma.
We found that in about 8% of lymphocytes, c-MYC and IgH are very close to
each other. Similar results were obtained for human fibroblasts.
gamma-Radiation leads to substantial changes in the chromatin structure of
stimulated lymphocytes: ABL and BCR genes are shifted to the nuclear
center, and mutual ABL-BCR distances become much shorter in the G1 and
S(G2) nuclei. Therefore, we hypothesize that the changes of chromatin
structure in the irradiated lymphocytes might increase the probability of a
translocation during G1 and S(G2) stages of the cell cycle. The fact that
the genes involved in the t(8;14) translocation are also located close
together in a certain fraction of cells substantiates the hypothesis that
physical distance plays an important role in the processes leading to the
translocations that are responsible for oncogenic transformation of cells.
Volume 89,
Issue 12,
pp. 4537-4545,
06/15/1997
Copyright © 1997 by The American Society of Hematology
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