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FLIEDNER, ANDREWS, CRONKITE AND BOND
characteristics, although an increased incidence of cell degeneration (karyo-
lysis and karyorrhexis) was found shortly after exposure. It may be expected
that such cell changes indicating direct injury occur more frequentty after
lethal or supralethal exposures, as seen in animal experiments.!°?° For the
evaluation of radiation effects on the bone marrow early after a single whole
body exposure (during the first 10 days), it was found satisfactory to count
500 erythroblasts per smear and to record the cytologic abnormalities encountered in all blood cell series. In dividing cells, the following changes
were considered abnormal: (1) tri- or multipolar mitoses of erythrocytic or
myelocytic precursors (fig. 4c); (2) mitoses with single or multiple chromo-
somal fragments “left behind” in the cytoplasm and apparently not further
participating in karyokinesis (fig. 1, D-G;fig. 2, H.; fig. 4 A,C); (3) mitoses
with chromosomal bridges in late ana- or telophase (fig. 1, A-C; fig. 4, B).
Other changes such as marked clumping or bizarre shapes and distribution
of chromosomes were not believed to be reliable enough to allow interpreta-
tion. In interphase cells, the following cytologic abnormalities were con-
sidered abnormal: (1) cells with one or more karyomeres in the cytoplasm
(fig. 1, H-M; fig. 2, G, I-R); (2) bi- or multinucleated erythrocytic or myelo-
cytic precursors, with or without an internuclear bridge, with or without
karyomeres (fig. 1 H,fig. 2, D, E, G; fig. 4, D-F); (3) giant cells, particularly
of the myelocytic series, which may be larger than any normal stage of development, i.e., huge promyelocytes or myelocytes. These cells mav have
the size of a more immature precursor but the nuclear and cytoplasmic characteristics of mature cells such as metamyelocytes, band forms, or segmented
neutrophils (fig. 2, A-C, N-O).
,
All of the cytologic abnormalities described here for the human bone marrow have been found in systematic studies in animals after various doses of
whole body irradiation.1*?1 In these experimental investigations, a dose relationship had been suggested for M. C. Abn. However, at supralethal dose
ranges, the immediate evidence of karyorrhexis and karyolysis was more
prominent than abnormalities seen in cells which attempted or completed
further proliferation.
The value of a cytologic evaluation of marrow smears after possible or
established radiation exposure is limited by the fact that all abnormalities
described are by no means radiation-specific although characteristic for
radiation effects. Such changes have been described in a variety of clinical
conditions and particularly in patients who have been given cytotoxic drugs
for the treatment of malignancies. Some of these cytologic alterations are
also seen, although infrequently, in smears of apparently healthy persons.**
The most extensive earlier studies have been performed by E. Schwarz®® and
L. Berman®? who also discussed their possible pathogeneses. Thus, the possibility that cytologic abnormalities in bone marrow smearsare dueto etiologic
factors other than radiation exposure has to be considered and ruled out. However, if they occur subsequent to known radiation exposure in persons presumably previously healthy, and appear and disappear at a characteristic time