PMID- 9192778
OWN - NLM
STAT- MEDLINE
DCOM- 19970710
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 89
IP  - 12
DP  - 1997 Jun 15
TI  - Distribution of ABL and BCR genes in cell nuclei of normal and irradiated 
      lymphocytes.
PG  - 4537-45
AB  - 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.
FAU - Kozubek, S
AU  - Kozubek S
AD  - Institute of Biophysics, Academy of Sciences, Brno, Czech Republic.
FAU - Lukasova, E
AU  - Lukasova E
FAU - Ryznar, L
AU  - Ryznar L
FAU - Kozubek, M
AU  - Kozubek M
FAU - Liskova, A
AU  - Liskova A
FAU - Govorun, R D
AU  - Govorun RD
FAU - Krasavin, E A
AU  - Krasavin EA
FAU - Horneck, G
AU  - Horneck G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Immunoglobulin Heavy Chains)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
SB  - IM
MH  - Cell Cycle
MH  - Cell Nucleus/chemistry/*radiation effects/ultrastructure
MH  - Chromosomes, Human, Pair 14/genetics/ultrastructure
MH  - Chromosomes, Human, Pair 22/genetics/radiation effects/*ultrastructure
MH  - Chromosomes, Human, Pair 8/genetics/ultrastructure
MH  - Chromosomes, Human, Pair 9/genetics/radiation effects/*ultrastructure
MH  - Fibroblasts/chemistry/radiation effects/ultrastructure
MH  - Fusion Proteins, bcr-abl/genetics
MH  - Gamma Rays
MH  - Genes, Immunoglobulin
MH  - *Genes, abl
MH  - Genes, myc
MH  - Humans
MH  - Immunoglobulin Heavy Chains/genetics
MH  - In Situ Hybridization, Fluorescence
MH  - Interphase
MH  - Lymphocytes/chemistry/*radiation effects/ultrastructure
MH  - Monte Carlo Method
MH  - *Philadelphia Chromosome
MH  - Translocation, Genetic
EDAT- 1997/06/15 00:00
MHDA- 1997/06/15 00:01
CRDT- 1997/06/15 00:00
PHST- 1997/06/15 00:00 [pubmed]
PHST- 1997/06/15 00:01 [medline]
PHST- 1997/06/15 00:00 [entrez]
AID - S0006-4971(20)58192-5 [pii]
PST - ppublish
SO  - Blood. 1997 Jun 15;89(12):4537-45.