EFFECTS OF WHOLE BODY IRRADIATION ON MARROW
483
sequence as shown in this paper, they can be used as an indicator of radia-
tion exposure.
The pathogenesis of the various abnormalities described cannot be deduced
from the marrow smears alone. However, time lapse photography of bone
marrow cells** and of tissue culture cells** after exposure to ionizing radiation has elucidated some of the possible mechanisms involved.
The appearance of free chromosomes or chromosomal fragments in abnormal mitoses are the result of partial or complete inhibition of polar movements of chromosomes or chromosomal fragments.*7 When the cell enters
interphase after completion of mitosis, these fragments apparently are transformed into small nuclear masses or droplets, the size of which may depend
in part on the number of chromosomesin the aberrant group (karyomeres).
Such aberrant nuclear fragments or karyomeres were found to be labeled with
tritiated thymidine in rats when it was injected 30 minutes prior to killing at
different times during the first 24 hours after whole body irradiation.!® This
would indicate that karyomeresarestill capable of synthesizing DNA synchro-
nously with the principal nucleus. Functionally, they must be considered as
‘satelite nuclei and not signs of karyorrhexis. Politzer, in 1934,57 suggested
that such nuclear fragments display signs of kinesis simultaneously with the
principal nucleus.
The appearance of chromosomal bridges in abnormal mitoses is a wellknownresult of radiation injury of cells and has been present in the marrow
smears examined in this study. In these smears they were felt to be recognizable with confidence only in late anaphase or telophase. It is conceivable
that the internuclear chromatin bridges found occasionally in interphase cells
originated from such mitotic chromosomal bridges. In autoradiographs of
marrow of the exposed persons incubated in vitro with tritiated thymidine, it
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was found in one instance that such an internuclear bridge was labeled as
well as the two nuclei connected by it.3* This indicates that such internuclear bridges are functionally still a part of the nuclei and enter DNA
synthesis synchronously.
The pathogenesis of giant cells with one or more nuclei is obscure. It is
conceivable to regard bi- or multinucleated erythrocytic or myelocytic cells
as the result of an undisturbed karyokinesis with an inhibited cytokinesis
which may be partial or complete. On this basis, one extreme would be to
find two cells connected only by a long fiber-like cytoplasmic bridge. An increased frequency of such cytoplasmic bridges between two cells was suggestive particularly in the marrow smears taken 3.5 years after the accident.
All transitions between a binucleated cell with a cytoplasm of normal outline
and two cells connected by a long cytoplasmic bridge could be found. The
pathogenesis of cells with three nuclei or of tripolar mitoses is not well understood although theories as to their formation have been proposed.®°** If bior multinucleated cells are able to complete their maturation, they can be
foundin the circulating blood. This was particularly true for the granulocytic
series in this study which showed abnormally large hypersegmented blood