of Human Bone Marrow after Accidental Exposure to Ionizing Radiation
465
The evaluation of the mitotic index of bone marrow is not a precise method
for calculations. It was pointed out by Japa’? and Unprrrz§ that the mitotic index in the normal marrow smears is lower when there is an immediate block of
mitotic activity®. Therefore only general conclusions about the mitotic activity
are possible. Under normal conditions, when the generation time and the mitotic
time of the multiplying cells is constant, the mitotic index reflects the degree of
proliferative activity. Whether or not this is true for human bone marrowinjured
by radiation is not known. In mammalian and plant radiation studies it was
found that radiation can cause a prolongation of the mitotic time!® 4. From
experimental studies in tissue culture it was concluded that radiation causes a
delay in different periods of the cell cycle??, finally resulting in a prolongation of
‘the generation time. In the bone marrow smears 12 and 44 hours after the radia-
tion accident, a relative increase in anaphases and telophases was observed, which
would be consistent with a prolonged mitotic time. Since many of the mitotic
figures were abnormal, the mitotic index in itself does not necessarily reflect at
the time intervals studied the proliferative capacity of the marrow. A prolonged
mitotic time due to a delay in anaphase and telophase would give a misleadingly
high mitotic index and thus the actual ‘‘active” mitotic index of undisturbed
cell divisions is probably very low.
From these preliminary data and from studies in rats? we believe that the
evaluation of the percentage of normal and abnormal mitotic figures, classified
into groups according to the severity of damage, might serve as another biologic
dosimeter. It would thus enhance the mitotic index, which fluctuates considerably
before minimal levels are reached at the time of severe and obvious marrow
damage. The observed radiation-induced abnormalities in the mitotic figures are
similar to those observed in other investigations of the effect of radiation on
mitoses, The usual staining method of marrow smears does not permit a detailed
investigation of mitotic abnormalities, since such methods arenot specific for desoxyribonucleic acid. Definite abnormalities were most frequently observed in late
metaphase, anaphase and telophase. In some mitotic figures chromosomes or
chromosomal fragments werelost. It is not known how long these hypoploid cells
can live and function. It is possible that chromosomal loss of bone marrow cells
occurs in the course of duplication and maturation!3. Observations of nuclear
swelling, chromatin dissociation, and release of nuclear material caused by ionizing
radiation were reported in cinematographic studies of irradiated fibroblasts in
tissue culture!4, Such abnormalities becamerare after 44 hours, and were absent
beyond the 4th day. It is therefore probable that “nuclear oedema’? of some
marrow cells is a primary effect of marrow cell damage at dose levels which are
not high enough to cause immediate karyolysis or karyorrhexis.
The formation of large myeloid and erythroid precursors is a complex phenomenon. In several cases their formation was due to nuclear division without
division of the cytoplasm. Thus binucleated giant myelocytes, normoblasts and
mature blood cells are formed. In several cases, however, giant cells were observed
35 London