|Chromosomes are composed of long thin molecules of DNA. When cells are
exposed to radiation or carcinogens, DNA sometimes breaks, and the broken
ends may rejoin in different patterns from their original arrangement.
The abnormalities that result are termed "chromosome aberrations"
and may be visualized at mitosis when cells divide.
The frequency of chromosome aberrations increases with radiation dose to
the cells and serves as an indicator of radiation dose received, i.e.,
a biological dosimeter. In vitro irradiation experiments using blood lymphocytes can provide a dose-response
relationship that can be used to estimate radiation dose to individuals
on the basis of the aberration frequency detected in their lymphocytes.
Among different types of aberrations, dicentric chromosomes are relatively
easy to detect, and their frequency is therefore useful as a biological
dosimeter. However, dicentric frequency declines within a few years because
the presence of two centromeres in one chromosome interferes with cell
division. Thus, the frequency of dicentric chromosomes can be applied to
recent exposure cases only. Since A-bomb survivors were exposed to radiation
many years ago, dicentric frequency is no longer useful for biodosimetry,
and the frequency of translocations (and inversions) is used instead. Such
aberrations have a single centromere per chromosome and hence can divide
so that the altered chromosome persists for many years. However, they were
more difficult to detect by conventional staining methods.
Figure 1 shows the relation between DS86 dose and the mean fraction of
cells with aberrations (mainly translocations) measured by conventional
staining in survivors exposed in typical Japanese houses in Hiroshima and
Nagasaki. The small but consistent differences between the two cities may
be due either to different scoring efficiency of aberrations in the two
laboratories or to differential errors in DS86 dose assignments.
. Relationship between fraction of cells with chromosome aberrations and
radiation dose to AHS survivors exposed in typical Japanese houses
|Currently, chromosome studies for survivors in both cities are examined
solely in the Hiroshima laboratory, using a modern chromosome painting
method (fluorescence in situ hybridization [FISH]). Chromosomes 1, 2, and 4 are stained yellow and other chromosomes
red so that translocations between yellow and red chromosomes can be detected
unambiguously (Figure 2). The FISH technique has made translocation detection
easier and more accurate and has been used successfully in studies of radiation
exposure accidents, such as Chernobyl.
. Metaphases labeled with fluorescence in situ
hybridization (FISH). The left metaphase
shows a normal cell and the right, a translocation indicated by arrows.
|Although fetuses had been regarded as radiosensitive, chromosome aberration
data for survivors irradiated in utero did not show a radiation effect when their blood lymphocytes were examined
at about 40 years of age. A mouse study also confirmed that chromosome
aberrations were not seen in offspring 20 weeks after in utero radiation exposure, although they were seen in mothers after exposure
Chromosome aberrations have been examined in clonally derived cell populations
in vivo (cells bearing an identical aberration) to see if clones show an increased
level of additional aberrations, which would indicate they have "genomic
instability." The results did not show an increased rate of later
aberrations indicative of genetic instability.
|References about this subject
||Nakano M, Kodama Y, et al.: Detection of stable chromosome aberrations by FISH in A-bomb survivors: Comparison with previous solid Giemsa staining data on the same 230 individuals. International Journal of Radiation Biology 2001; 77:971-7
||Kodama Y, Pawel D, et al.: Stable chromosome aberrations in atomic bomb survivors: Results from 25 years of investigation. Radiation Research 2001; 156:337-46
||Ohtaki K, Kodama Y, et al.: Human fetuses do not register chromosome damage inflicted by radiation exposure in lymphoid precursor cells except for a small but significant effect at low doses. Radiation Research 2004; 161:373-9
||Nakano M, Kodama Y, et al.: Chromosome aberrations do not persist in the
lymphocytes or bone marrow cells of mice irradiated in utero or soon after birth. Radiation Research 2007; 167:693-702
||Kodama Y, Ohtaki K, et al.: Clonally expanded T-cell populations in atomic bomb survivors do not show excess levels of chromosome instability. Radiation Research 2005; 164:618-26