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Blood, 15 August 2002, Vol. 100, No. 4, pp. 1513-1514
CORRESPONDENCE
To the editor:
Frequency of BCL-2/JH translocation in
healthy males exposed to low-level radiation in comparison to
age-matched healthy controls
The t(14;18) translocation has been detected by cytogenetic and
molecular techniques in about 90% of follicular lymphomas, 50% of
adult undifferentiated lymphomas, and 20% of diffuse large-cell lymphomas. Based on Southern blot and polymerase chain
reaction (PCR) analysis, 50% to 60% of follicular lymphomas
carry t(14;18)-MBR-translocations.1 The occurrence of
t(14;18) is not restricted to malignant lymphoma: 50% to 60% of
healthy individuals were found to carry t(14;18)-MBR-positive cells
detectable by sensitive PCR techniques.2-4 Therefore, the number of circulating t(14;18)-positive cells might serve as an indicator for environmental exposure to carcinogens and possibly correlate with the cumulative risk of developing t(14;18)-positive non-Hodgkin lymphoma (NHL).5 Since ionizing
radiation can induce chromosomal translocations in human cells in
vitro, for example, t(9;22) and t(8;21),6 we initiated
this study to investigate whether exposure to low-level radiation has
an influence on the frequency as well as the total number of
circulating t(14;18)-positive cells in healthy individuals, that is,
the generation of the translocation as well as clonal expansion or
progression.7 At the occasion of routine health checks, peripheral blood samples were
obtained with informed consent from 131 healthy male employees working
at the local nuclear power plant (NPP) in Lubmin, Germany.
They were grouped according to their total cumulative radiation dose
exposure: group A, < 50 mSv (n = 61); B, 50-100 mSv (n = 34); C,
100-200 mSv (n = 24); and D, 200-400 mSv (n = 12). Serving
as controls were 131 age-matched male healthy volunteers with no
previous radiation exposure. DNA was extracted from peripheral blood
mononuclear cells (PBMNCs) by standard procedures, quantitated spectrophotometrically, and stored at  80°C. The real-time quantitative PCR technique used for the detection of
BCL-2-MBR/IgH -rearrangements has been described in
detail.8 At least 5 1.0 µg aliquots of cellular DNA
(~5 × 140 000 cells) isolated from each blood sample were tested
for the presence of the t(14;18) translocation. To determine the total
number of cells tested, 3 0.1 µg DNA aliquots were quantitatively
analyzed for K-ras. All amplification products were analyzed by agarose
gel electrophoresis for the presence of several t(14;18) DNA fragments; 28 amplification products were selected for nucleotide sequence analysis because they revealed t(14;18)-DNA fragments of a quite similar size. In no case were identical sequences found. The frequency of BCL-2-MBR/JH translocation in
peripheral blood lymphocytes from healthy males working at a nuclear
power plant was 60.3% (79/131), which is statistically not different from the frequency of 55% (72/131) in age-matched healthy controls (Table 1). At least 700 000 cells (~5
µg cellular DNA) were tested per individual based on the quantitative
determination of the K-ras gene. There were no statistical differences
between the frequency of BCL-2/JH translocation
observed in the 4 groups of NPP workers defined by increasing
cumulative radiation exposure as well as between the frequency in these
4 groups and age-matched healthy controls (Table 1). Furthermore, the
incidence of more than one t(14;18)-positive cell clone was about the
same in both study populations. The quantitative determination of
circulating t(14;18)-positive cells (Figure
1) revealed no significant differences between NPP workers and age-matched healthy controls.
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Table 1.
Frequency of BCL-2/JH
translocation in peripheral blood lymphocytes from males working at a
nuclear power plant and from age-matched healthy male volunteers
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| Figure 1.
BCL-2-MBR/JH
translocation-carrying cells in NPP workers and in healthy controls.
Total number of circulating BCL-2-MBR/JH
translocation-carrying cells in t(14;18)-positive healthy males
working at a nuclear power plant ( ) grouped according to their
cumulative radiation exposure (see Table 1) and age-matched healthy
controls ( ). There were no significant differences between NPP
workers and healthy controls as well as their subgroups, A to D (Mann
Whitney test; all positive individuals: P = .19; subgroup
A, P = .45; B, P = .15; C,
P = .46; D, P = .51).
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Based on these results it may be concluded that low-level radiation
exposure up to 400 mSv has no significant effect on the frequency of
the t(14;18) translocation as well as the total number of circulating
t(14;18)-positive cells in the individuals studied. At present,
possible effects of higher cumulative doses cannot be excluded.
Lars Dölken, Frank Schüler, and Gottfried Dölken
Correspondence: Gottfried Dölken, Klinik und Poliklinik
für Innere Medizin C, Hämatologie und Onkologie,
Ernst-Moritz-Arndt-Universität Greifswald, Sauerbruchstr, D-17487
Greifswald, Germany; e-mail: doelken{at}mail.uni-greifswald.de
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