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iological Indicators

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isual curve (Fig.
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inimals [1]. It is
il 30 day mortal-

cell survival, obtained by using the 7Ti// and

McCullough spleen colony assay. The curve
represents composite data obtained over the
course of years by the hematology group in the
Medical Department at Brookhaven. Of the

ting from deple-

ion in the bone
ithreference to

‘system ofinter-

many such curves that have been obtained with

ich are the stem
Fig. 1).

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The first constituent function of the doseresponse curve in Figure 2 is shown in Figure 3.
This is simply a “dose-effect” curve. for stem

ype distribution,
e distribution of

photons, most appear to have no “shoulder.”
However. occasionally a small shoulder may

appearto be present. The function is dotted from

In Figure 4, and with reference first to the

left ordinate only. one sees (“cell survival” curve)
the same function plotted in Figure 3, but now on
arithmetic rather than semi-logarithmic coordinates. However, also shownis the inverse ofthis
curve, representing the severity of effect on the

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permits one to obtain a quantitative measure of
the severity of effect on the parent organ system.
Theresults of thus using severity of effect as the
independent variable is shown in Figure 5. Note
that the scale for severity of effect is simplythe
fraction (or percentage) of stem cells killed,
which mustof course saturate at 1.0 (100% ). The
resulting curve is extraordinarily steep: however,
this is merely a matter of scaling. If one expands
the scale (Fig. 6). the S-shaped curveis regained.
It is then also obvious that the severity of

effect can be used as the independent variable,
in terms of which the mortality rate of the ani' mals maybe described and thus predicted. It
becomesclearthat. if one does have a quantitative
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Mouse Mortality —=

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Fig. 4. Plot showing the relationships among the
curves for stem cell survival. severity of organ effect
and mouse mortalityrate. all as a function of dose.

about 6 Gy on becauseof technical difficulties
associated with having to inject large numbers
of bone marrowcells in order to detect the few
remaining viable stem cells.

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Fig. 3. A conventional plot for the log of the fraction of surviving colony-forming units-spleen
(CFU-S)(hematopoietic stem cells) as a function of
dose. The fitted function intersects the ordinate ata
value somewhatabove unity indicating that the curve
mayhave a small shoulder.

oroken downinto

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ale of severity of
dicine, it is first

dose mortality
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Stern Cell Survival (CFU-S)

mortality in the
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relevant organ, the bone marrow. When thefrac-

tion of the remaining stem cells becomes quite
low, on the order of less than !% (meaning that
the effect on the relevant organ. the bone marrow,
Is severe indeed), the more sensitive animals begin
to die, forming the initial part of the mortality
response curve indicated on the right ordinate.
It is then obvious that the mortality rate

erence
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response funciber of animals
‘the dose of the
i¥S}. These data

amongthe cellular elements of the organ system

can be used as a “biological indicator,” which

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Severity of Effect

Fig. 5. The second constituent curve. for mouse mortality as a function ofthe severity of effect on the
bone marrow. Note that the line is indistinguishable
from linear. but does deviate slightly trom the vertical.

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