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FLIEDNER, ANDREWS, CRONKITE AND BOND
cells during the first 2-4 days after exposure. They are known to occur under
experimental conditions!” and may be as frequent as 50-60 per cent ofall
granulocytesafter very high radiation doses.*® In the erythropoietic series, the
final enucleation of multinucleated cells may result in the appearance of
some macrocytes.
An alternative possibility for the formation of multinucleated cells after
radiation exposure is the fusion of two mononucleated cells. This has been
demonstrated by time lapse photography of marrow cells** and of tissue
culture cells.25 It is unknown what proportion of these abnormalcells originates from inhibited cytoplasmic division with complete nuclear division
and what proportion from cell fusion.
Although not proven, mononucleated giant cells may be the result of a
disturbed cyto- and karyokinesis with continued DNA synthesis and uninterrupted cellular maturation. The occurrence of a skipping of cell division
in erythropoiesis has been postulated by Stohlman*® in various states of
erythropoietic activity and is suggestive in this study also for the white cell
series early after irradiation. Such skipping of cell division with undisturbed
cell maturation results in the net production of only
2n
(if n is the number
of skipped divisions) of the cells produced normally. Thus, the slope of
granulocyte diminution early after whole body exposure is not only the result
of interrupted new production at the stem cell level*! but is modified by the
degree of mitotic inhibition of precursor cells.
The presence of cytologic abnormalities 3.5 years after the accident, as
indicated by some mitotic abnormalities, and an increase in the frequency of
binucleated early erythroblasts is poorly understood. Chromosomal abnormalities were demonstrated in blood leukocyte cultures of these men by Bender.1®
The abnormalities seen in the bone marrow can befoundin all those clinical
conditions associated with an increased regeneratory activity of hemopoiesis,
such as various forms of anemia, but they are also seen in leukemias.2253 The
cell counts of the peripheral blood in these men,‘? as well as the mitotic
indices in the marrow, were well within normal limits. Thus, the abnormalities
shown mayindicate a slight increase in an “ineffective” hemopoiesis although
the pathogenesis and significance are not established and must await longterm follow-up studies.
SuMMARY
1. Serial marrow studies were performed during the first few days in
eight men accidentally exposed to a mixed neutron gammairradiation. They
showed the occurrence of a wave of cytologic abnormalities. These were
identical with those seen in animal experiments 1-3 days after whole body
irradiation. They were considered to be “mitotically connected” (M. C. Abn.)
and included the occurrence of chromosomal bridges and chromosomalfragmentsin mitoses. In interphase cells, the main abnormalities were nuclear fragments (“karyomeres”) in the cytoplasm of erythroblasts, myelocytic cells and
lymphocytes; bi- and multinucleated cells; and giant cells. The peak of ab-