ON THE ROLE OF SPONTANEOUS ADDITIONAL SYNTHESIS IN FORMATION
OF RADIATION INDUCED ABERRATIONS OF CHROMOSOMES
H.A.Hakimov a , G.F.Mahmudova a, R.A.Jakubova a , E.A.Latypova a , A.P.Akifyev b
a
Institute of Genetics and Experimental Biology of Plants, Academy of Science of
Uzbekistan , Tashkent, Republic of Uzbekistan
b
Institute of General Genetics, Russian Academy of Science, Moscow, Russia
The sudden discrepancy between the amount of primary damages in DNA and a final
number of chromosomal aberrations is one of a phenomena which was found out during
studying of features of the process of chromosomal mutagenesis in eukaryotic cells and
cannot be explained from the point of view of classical concepts. Biologically significant
dozes of ionizing radiation produce primary damages in DNA, only very insignificant part of
which (about 1-2 %) constitutes a non-repaired component (Rydberg, 1985).
One more fact demanding special attention and studying is differential sensitivity of
euchromatin and heterochromatin chromosome parts to ionizing radiation action (Slijepcevic
Р., Natarajan А., 1994). Moreover, distribution of targets for formation of exchange
chromosome aberrations (ECA) on the length of a chromosome is also not casual (Thucker J.,
Senft J., 1994). Besides a number of researchers note a special role of minor fraction DNA,
associated with a nuclear matrix, in formation of EAC (Yasuyi, et al, 1996, Ganassy, et al,
1986).
In our own researches which were carried out earlier on animal and plant cells, a
specific character of radiosensitizing effect of thymidine analogue 5-bromo-2’-deoxyuridine
(BrdU) in various phases of a cellular cycle was found out. It proved to be, that incorporation
of BrdU into the minor fraction of DNA (a component, which is no more than 1-2 % genome
DNA) in GO, G1 and G2 - phases results to cytogenetic effect (on a criterion of chromosome
aberrations), which is comparable with the same in S-phase. Analysis of our own data and
other research’s outcomes
allows to make the assumption that this effect is caused by
incorporation of BrdU into DNA within the framework of spontaneous additional synthesis
(SAS) DNA, which is topologically connected with nuclear matrix.
In the present
work, incubation of PHA–stimulated human lymphocytes
with
Ethoposyde - an inhibitor of Topo II led to specific character of modifying of ionizing
radiation effect by BrdU. Studying the spectrum of aberrations of the chromosomes formed
as a result of combined action of BrdU and Ethoposyde in GO, G1 and G2-phases of a
cellular cycle, indicate a specific role of spontaneous additional synthesis DNA in forming
EAC.