ISSN 1022-7954, Russian Journal of Genetics, 2006, Vol. 42, No. 10, pp. 1116–1126. © Pleiades Publishing, Inc., 2006.
Original Russian Text © Yu.E. Dubrova, 2006, published in Genetika, 2006, Vol. 42, No. 10, pp. 1335–1347.
As one of former students of Yuri Petrovich
Altukhov, I would like to emphasize his great contribu-
tion to developing new approaches to monitoring of
mutations induced in human germline cells . The
ideas of Yuri P. Altukhov had a tremendous impact on
my formation as geneticist. Many things that I am
doing now are in some way related to the experience
that I gained working at his lab.
Genetic consequences of radiation and chemical
mutagens have been studied at my laboratory for sev-
eral years. Traditionally, studies in this ﬁeld involve
analysis of mutation frequency in the offspring of par-
ents treated with radiation or chemical mutagens . To
put it differently,
of mutations in germline
cells of organisms treated with mutagens is examined.
The results of numerous studies have shown that
mutagens cause diverse primary lesions of DNA struc-
ture, which, in turn, either directly produce mutations,
or serve as permutation damage sites, some of which
after repair may result in mutations . According to
this scheme, genetic risk of mutagenic effect is associ-
ated only with transmission of de novo mutations to the
offspring and their transgenerational manifestation .
However, ample evidence, obtained in the last two
decades, suggests that the views, currently accepted in
radiation genetics, may signiﬁcantly underestimate del-
eterious effects of mutagens on living organisms. I
mean the phenomenon of radiation-induced genomic
instability, in which high mutation rate is observed not
only in the directly irradiated cells, but also during a
long time in their unirradiated offspring [3–5].
The “memory” of irradiated cells is impressive:
according to numerous studies, signiﬁcantly elevated
mutation rate in cell culture is observed for at least 20
to 40 cell divisions after the initial irradiation [3–5].
These results generated several hypotheses that explain
elevated prevalence of cancers in irradiated individuals
not only by direct mutation induction in the irradiated
cells, but also by a signiﬁcant contribution of the
genomic instability, manifested after irradiation [6–8].
According to these hypotheses, radiation-induced
genomic instability may considerably intensify muta-
tion accumulation in somatic cells, further promoting
their carcinogenic transformation. These views con-
form to Loeb’s theory, which states that instability of
early cancer cells is an essential component of their
oncogenic transformation .
Note that the phenomenon of radiation-induced
genomic instability, albeit well studied in vitro,
requires further veriﬁcation by in vivo studies . The
most signiﬁcant problems in this ﬁeld concern extrapo-
lation of the results on the radiation risk factors to
humans. The corresponding experimental data,
obtained in the last few years for humans, are very con-
tradictory. The results of some studies suggest instabil-
ity in somatic cells of individuals during long time after
radiation exposure [10, 11], whereas other studies
report the lack of such instability .
The results of studying radiation-induced genomic
instability in somatic cells indicate that analogous pro-
cesses may occur in germline cells, which can enhance
mutation rate in the progeny of radiation-exposed par-
ents. Indeed, the experimental data accumulated in the
last years suggest the existence of such effects, detected
several generations after the parental exposure (see
[13–17] for review). In the present paper, the results of
these studies are summarized and possible mechanisms
of genomic instability, observed in the offspring of irra-
diated parents, are discussed.
Genomic Instability in the Offspring of Irradiated Parents:
Facts and Interpretations
Yu. E. Dubrova
Department of Genetics, University of Leicester, Leicester LE17RH, United Kingdom
Fax: (44-116) 252-33-78; e-mail: firstname.lastname@example.org
Received March 22, 2006
—This review is devoted to genomic instability in the offspring of parents that were irradiated or
treated with chemical mutagens. The evidence is presented, showing high frequency of cancer diseases and
instability of the genome of somatic and germline cells in the offspring of radiation-exposed animals. Possible
epigenetic mechanisms of these effects are considered, as well as their signiﬁcance as components of genetic
factors of radiation risk for humans.