1062-3604/01/3201- $25.00 © 2001
Russian Journal of Developmental Biology, Vol. 32, No. 1, 2001, pp. 44–50. Translated from Ontogenez, Vol. 32, No. 1, 2001, pp. 51–57.
Original Russian Text Copyright © 2001 by Pelevina, Gotlib, Kudryashova, Antoshchina.
The main biological consequences of the action of
ionizing radiation on the cell genome include irrevers-
ible changes in the processes of DNA replication and
repair (Wright, 1998). Most of these changes manifest
themselves immediately after irradiation. However, it
was shown that the radiation-induced loss of reproduc-
tive capacity may be delayed for as long as six replica-
tion cycles (Puck and Marcus, 1956; Elkind and Sutton,
1959). Subsequent studies showed that the loss of
reproductive potential (lethal mutations or delayed
reproductive death) in the progeny of irradiated cells
persists for many generations (Gotlib
, 1985; Sey-
mour and Mothersill, 1986; Gorgojo and Little, 1989).
In addition to delayed cell death, the progeny of irradi-
ated cells are characterized by the delayed appearance
of mutational changes, including speciﬁc gene muta-
tions (Chang and Little, 1992; Harper
, 1997) and
chromosome aberrations (Kadhim
, 1992, 1998;
, 1997; Wright, 1998).
Thus, the surviving progeny of irradiated cells are
liable to nonlethal changes that can be inherited for
many generations, manifesting themselves in delayed
effects. This phenomenon, named genomic instability,
is apparently responsible for the remote consequences
of irradiation. It is assumed that genomic instability
includes the processes of rearrangement, recombina-
tion, and translocation in the genome, along with gene
ampliﬁcation, expression, and suppression (Murnane
and Sprung, 1997). All these events apparently deter-
mine cell fate.
However, the mechanism responsible for the induc-
tion of genomic instability is still unclear. In particular,
this concerns the chain of events from the initial dam-
age to its eventual remote effects, especially in the case
of low radiation doses.
The purpose of this work was to study the develop-
ment of some genetic and cellular responses in the
progeny of irradiated cells for more than 30 genera-
tions. Cells were exposed to acute and chronic
ation from a
source at high and low doses.
MATERIALS AND METHODS
Experiments were performed with an asynchronous
HeLa cell population and Chinese hamster ﬁbroblasts
(strain 237) at the exponential growth phase. Cells in a
-irradiated in a GUT-
a dose rate of 0.5 Gy/min; in another experimental vari-
ant, the cells were exposed in the 10-km zone around
the Chernobyl Nuclear Power Plant for one to six days
(dose rate ~0.01–0.1 Gy/h). The cells were cultivated
and ﬁxed as described by Gotlib
clonogenic capacity was determined by the conven-
tional method (Puck and Marcus, 1956). Cytogenetic
preparations were made by putting drops of cell sus-
pension on chilled coverslips and drying them in the air.
The frequency of cells with micronuclei (MN) in no
less than 1000 cells per point was determined for more
than 30 generations after irradiation.
MN yield in the progeny of individual cells surviv-
ing irradiation was studied by means of clonal analysis.
Cells in a suspension were irradiated at doses of 3.0 and
0.5 Gy and incubated for nine days. Colonies formed
during this period were carefully removed from glass,
placed in individual wells of a 24-well plate, and incu-
bated for 12 days. Thereafter (i.e., 21 days after irradi-
ation), monolayers formed in each well were treated
with trypsin and ﬁxed by conventional methods.
Stained preparations were used for analyzing the fre-
quencies of cells with MN in the progenies of individ-
ual irradiated cells (no less than 1000 cells per clone).
Remote Consequences of Irradiation
for the Progeny of Mammalian Cells
I. I. Pelevina, V. Ya. Gotlib, O. V. Kudryashova, and M. M. Antoshchina
Semenov Institute of Chemical Physics, Russian Academy of Sciences, ul. Kosygina 4, Moscow, 117977 Russia
Received July 5, 2000
—It is shown that
-irradiation has remote consequences for mammalian cells cultivated
Many generations in the progeny of cells surviving acute and chronic irradiation at high and low doses are char-
acterized by a number of abnormalities, including delayed cell death, the formation of micronuclei and giant
cells, an increased frequency of sister chromatid exchanges, a reduced potential for repair, the loss of adaptive
response, and increased radiosensitivity. These phenomena are regarded as manifestations of genomic instabil-
ity induced by ionizing radiation.
: progeny of irradiated cells, remote consequences, micronuclei.
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